Efficacy Study of Different Laboratory Management Strateg... | NCT02028676 | Trialant
NCT02028676
Sponsor
Medical Research Council
Status
Completed
Last Update Posted
Jun 6, 2014Estimated
Enrollment
1,206Actual
Phase
Phase 4
Conditions
Human Immunodeficiency Virus
Interventions
Clinically Driven Monitoring (CDM)
Laboratory plus Clinical Monitoring (LCM)
Arm A: ABC+3TC+NNRTI
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI maintenance
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC maintenance
Once-daily ABC+3TC
Twice-daily ABC+3TC
Continued cotrimoxazole prophylaxis
Stopped cotrimoxazole prophylaxis
Countries
Uganda
Zimbabwe
Protocol Section
Identification Module
NCT ID
NCT02028676
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
G0300400
Secondary IDs
ID
Type
Description
Link
24791884
Registry Identifier
ISRCTN
G0300400
Other Grant/Funding Number
UK Medical Research Council
Brief Title
Efficacy Study of Different Laboratory Management Strategies and Drug Regimens in HIV-infected Children in Africa
Official Title
A Randomised Trial of Monitoring Practice and Induction Maintenance Drug Regimens in the Management of Antiretroviral Therapy in Children With HIV Infection in Africa
Acronym
ARROW
Organization
Medical Research CouncilOTHER_GOV
Status Module
Record Verification Date
Jun 2014
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 2007
Primary Completion Date
Mar 2012Actual
Completion Date
Jun 2012Actual
First Submitted Date
Dec 31, 2013
First Submission Date that Met QC Criteria
Jan 4, 2014
First Posted Date
Jan 7, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Jan 15, 2014
Results First Submitted that Met QC Criteria
Jun 4, 2014
Results First Posted Date
Jun 6, 2014Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jun 4, 2014
Last Update Posted Date
Jun 6, 2014Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Diana M Gibb, Professor of Epidemiology, Medical Research CouncilPrincipal Investigator
Lead Sponsor
Medical Research CouncilOTHER_GOV
Collaborators
Name
Class
Department for International Development, United Kingdom
OTHER_GOV
ViiV Healthcare
INDUSTRY
GlaxoSmithKline
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The two original objectives were to determine in HIV-infected children initiating antiretroviral therapy (ART):
Whether clinically driven monitoring (CDM) will have a similar outcome in terms of disease progression or death as routine laboratory and clinical monitoring (LCM) for toxicity (haematology/biochemistry) and efficacy (CD4)?
Whether induction with four drugs from two ART classes followed by maintenance with three drugs after 36 weeks be more effective than a continuous non-nucleoside reverse transcriptase inhibitors (NNRTI)-based triple drug regimen in terms of CD4 and clinical outcome?
Two secondary objectives were to determine
Whether changing from twice daily lamivudine+abacavir to once daily lamivudine+abacavir after 48 weeks on ART will have a similar outcome in terms of virological suppression and will result in improvements in adherence to ART?
Whether stopping daily cotrimoxazole prophylaxis in children over 3 years of age who have been on ART for at least 96 weeks has a similar outcome in terms of hospitalisation or death as continuing daily cotrimoxazole?
Detailed Description
The ARROW (AntiRetroviral Research fOr Watoto) protocol describes an open-label randomised trial primarily evaluating two strategic approaches for management of antiretroviral therapy (ART) in 1200 symptomatic HIV-infected infants and children initiating ART following WHO guidelines in Uganda and Zimbabwe. The first strategy compares clinically driven monitoring (CDM) with laboratory plus clinical monitoring (LCM). In both groups, tests for toxicity (standard haematology and biochemistry panels) and efficacy (lymphocyte subsets including CD4 count) will be done every 12 weeks. In LCM, all results will be returned for patient management. In CDM, physicians may request results from routine haematology/biochemistry panels if needed for clinical management, but results will not be returned routinely, and lymphocyte subsets will never be returned. Extra laboratory tests may be requested outside of the scheduled visits at any time in either group (except for lymphocyte subsets in CDM). The second strategy compares a continuous WHO-recommended first-line ART three-drug two-class regimen, comprising two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) plus one Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), with induction with four drugs (two classes) for 36 weeks followed by maintenance with three drugs. After at least 36 and 96 weeks on ART respectively, two further randomisations will assess simplification strategies which could improve long-term ART adherence (i) once versus twice daily lamivudine+abacavir NRTI drugs (ii) stopping versus continuing daily cotrimoxazole prophylaxis.
Conditions Module
Conditions
Human Immunodeficiency Virus
Keywords
HIV
Africa
children
antiretroviral therapy
laboratory monitoring
toxicity
CD4
induction maintenance
cotrimoxazole
prophylaxis
abacavir
lamivudine
once daily
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 4
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
1,206Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Clinically Driven Monitoring (CDM)
Experimental
Other: Clinically Driven Monitoring (CDM)
Laboratory plus Clinical Monitoring (LCM)
Active Comparator
Other: Laboratory plus Clinical Monitoring (LCM)
Arm A: abacavir (ABC)+lamivudine (3TC)+NNRTI
Active Comparator
ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO non-nucleoside reverse transcriptase inhibitor (NNRTI): either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Drug: Arm A: ABC+3TC+NNRTI
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI maintenance
Experimental
ZDV [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Drug: Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI maintenance
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Clinically Driven Monitoring (CDM)
Other
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
LCM vs CDM: Disease Progression to a New WHO Stage 4 Event or Death
Number of participants with disease progression to a new WHO stage 4 event or death, to be analysed using time-to-event methods
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
LCM vs CDM: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV
Number of participants with a new Grade 3 or 4 adverse event (AE), not solely related to HIV, to be analysed using time-to-event methods
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
Induction ART: Change From Baseline in CD4% 72 Weeks After ART Initiation
Baseline, 72 weeks
Induction ART: Change From Baseline in CD4% to 144 Weeks From ART Initiation
Baseline, 144 weeks
Induction ART: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV
Number of participants with a new grade 3 or 4 adverse event (AE), not solely related to HIV, to be analysed using time-to-event methods
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
Once Versus Twice Daily Abacavir+Lamivudine: Suppressed HIV RNA Viral Load 48 Weeks After Randomisation
Number of participants with HIV RNA viral load <80 copies/ml at 48 weeks. Measured retrospectively on stored plasma specimens: due to low stored volumes from some children, samples had to be diluted and therefore a threshold of <80 copies/ml was used to indicate suppression.
48 weeks
Once Versus Twice Daily Abacavir+Lamivudine: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV, Judged Definitely/Probably or Uncertain Whether Related to Lamivudine or Abacavir
Secondary Outcomes
Measure
Description
Time Frame
LCM vs CDM, Induction ART: All-cause Mortality
Number of participants who died from any cause, to be analysed using time-to-event methods
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
Induction ART: New WHO Stage 4 Event or Death
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
For initial randomisation to CDM vs LCM, and to ART induction strategy:
Inclusion Criteria:
Children should have an adult carer in the household who is either:
participating in the DART trial OR
being treated with ART OR
HIV positive but not yet needing treatment but with access to a treatment programme when ART is required OR
HIV negative. Children of DART participants should have first priority on any available remaining slots to enter ARROW.
Parents or guardians, and children where appropriate according to age and knowledge of HIV status, must be willing and able to give informed consent for randomisation to CDM or LCM and to first-line ART strategy.
Participants must have a confirmed documented diagnosis of HIV-1 infection:
For children aged under 18 months: two separate peripheral blood specimens from different days, both results being positive with HIV-DNA polymerase chain reaction (PCR).
For children aged 18 months or over: antibody positive serology by ELISA test (confirmed by licensed second ELISA or Western Blot) or WHO approved rapid test (performed in series) both on the same sample. Any child previously tested at another clinic should have a repeat test at an ARROW screening laboratory to confirm their status.
Age 3 months to 17 years (13-17 years to be capped at 10%)
ART naïve (except for exposure to perinatal ART for the prevention of mother-to-child HIV transmission).
Meeting criteria for requiring ART according to WHO stage and CD4 percent or count:
WHO paediatric clinical stage IV disease: treat regardless of CD4 percent or count
WHO paediatric clinical stage III disease:
<12 months: treat all
>12 months: treat all children irrespective of the CD4 percent or count; however, in children aged > 12 months with tuberculosis, lymphocytic interstitial pneumonia (LIP), oral hairy leukoplakia (OHP) or thrombocytopenia (low platelet count treat) be guided by CD4 cell assays (see below).
WHO paediatric clinical stage II or I disease: treat guided by CD4 percent or count
CD4%<25% for infants <12 months;
CD4%<20% for children 1-<3 years;
CD4% <15% for children 3-<5years;
CD4% <15% for children > 5years (consideration should also be taken of the CD4 count. A CD4 count <200 cells/mm3 can be used to guide starting ART and CD4 should generally be <350 cells/mm3.)
Exclusion Criteria:
Cannot, or unlikely to attend regularly (e.g. usual residence too far from study centre)
Likelihood of poor adherence
Presence of acute infection (e.g. malaria, helminthiasis, acute hepatitis, acute pneumonia, septicaemia, meningitis). Children may be admitted after recovery of an acute infection. Children with chronic lung disease, including recurrent respiratory infections, are eligible. Children with tuberculosis (TB) will not be enrolled while on the intensive phase of anti-tuberculosis therapy, but should be re-evaluated after the intensive phase and a decision made then about starting ART (see 4 below)
In receipt of medication contraindicated by ART
children under three years of age receiving anti-tuberculosis therapy should not be enrolled (as they will have to receive nevirapine).
on chemotherapy for malignancy
Laboratory abnormalities which are a contra-indication for the child to start ART (haemoglobin <8.5g/dL; neutrophils <0.50x109/L; aspartate transaminase (AST) or alanine transaminase (ALT) >5 x the upper limit of normal (ULN); grade 3 renal dysfunction - creatinine >1.9 x ULN).
N.B. causes of anaemia, such as concurrent bacterial infection, malaria, helminthiasis and/or malnutrition should be investigated, and treatment for anaemia and its causes commenced prior to re-screening for eligibility.
Being pregnant or breast-feeding an infant
Perinatal exposure to nevirapine (either through prevention of mother-to-child transmission (pMTCT) or breastfeeding) for children aged 3 - 6 months only
Eligibility criteria for the secondary randomisation to once vs twice daily lamivudine+abacavir Inclusion criteria
Participating in ARROW
On ART for at least 36 weeks
Currently taking lamivudine+abacavir twice daily as part of their ART regimen and expected to stay on these two drugs for at least the next 12 weeks
Parents or guardians, and children where appropriate according to age and knowledge of HIV status, must be willing and able to give informed consent for randomisation to once or twice daily lamivudine+abacavir
Exclusion criteria
Likely to switch to second-line therapy in the next 12 weeks
Eligibility criteria for the secondary randomisation to stop or continue cotrimoxazole prophylaxis randomisation Inclusion criteria
Participating in ARROW
Aged at least 3 years
Initiated ART at least 96 weeks previously, and received at least 96 weeks of ART allowing for any interruptions in ART
Currently prescribed daily cotrimoxazole as primary prophylaxis
Parents or guardians, and children where appropriate according to age and knowledge of HIV status, must be willing and able to give informed consent for randomisation to stop or continue daily cotrimoxazole prophylaxis
If living in a malaria endemic area, has an insecticide treated bednet and prepared to use this for the child.
Exclusion criteria
Previous diagnosis of Pneumocystis jiroveci pneumonia (cotrimoxazole is secondary prophylaxis and should not be discontinued)
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
3 Months
Maximum Age
17 Years
Standard Ages
Child
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Diana M Gibb, MD
Medical Research Council
Principal Investigator
Peter Mugyenyi, PhD
Joint Clinical Research Centre, Kampala, Uganda
Principal Investigator
Kusum Nathoo, PhD
University of Zimbabwe, Harare, Zimbabwe
Principal Investigator
Adeodata Kekitiinwa, MD
Baylor College of Medicine Children's Foundation, Mulago, Uganda
Principal Investigator
Paula Munderi, MBChB
MRC /UVRI Uganda Research Unit on AIDS, Entebbe, Uganda
Principal Investigator
Victor Musiime, PhD
Joint Clinical Research Centre, Kampala, Uganda
Principal Investigator
Mutsa F Bwakura-Dangarembizi, MBChB
University of Zimbabwe, Harare, Zimbabwe
Principal Investigator
Philippa Musoke, PhD
Baylor College of Medicine Children's Foundation, Mulago, Uganda
Principal Investigator
Sabrina Bakeera-Kitaka, MBChB
Baylor College of Medicine Children's Foundation, Mulago, Uganda
ARROW Trial team. Routine versus clinically driven laboratory monitoring and first-line antiretroviral therapy strategies in African children with HIV (ARROW): a 5-year open-label randomised factorial trial. Lancet. 2013 Apr 20;381(9875):1391-1403. doi: 10.1016/S0140-6736(12)62198-9. Epub 2013 Mar 7.
There were two additional nested substudy randomizations after initial trial enrolment (see inclusion/exclusion criteria for eligibility). From 8/2009 to 6/2010, eligible children were randomized to once vs twice daily abacavir+lamivudine. From 9/2009 to 2/2011, eligible children were randomized to stop vs continue cotrimoxazole prophylaxis.
Recruitment Details
All recruited children (n=1206) were randomly assigned to CDM vs LCM and the three different induction ART strategies at enrolment (3/2007-11/2008). This was a factorial randomisation meaning that the children were effectively randomized into 6 parallel groups. Baseline characteristics are presented below separately for each initial randomization.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Clinically Driven Monitoring (CDM)
Clinically Driven Monitoring (CDM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Periods
Title
Milestones
Reasons Not Completed
Initial Enrolment: CDM vs LCM
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Factorial Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC maintenance
Experimental
ZDV [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Drug: Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC maintenance
Once-daily ABC+3TC
Experimental
ABC [abacavir]: syrup or tablet, dosed once-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed once-daily according to weight-bands following WHO
Drug: Once-daily ABC+3TC
Twice-daily ABC+3TC
Active Comparator
ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO
Children had been taking once-daily cotrimoxazole prophylaxis since at least ART initiation. Children randomised to this experimental arm stopped taking cotrimoxazole prophylaxis.
Other: Stopped cotrimoxazole prophylaxis
Clinically Driven Monitoring (CDM)
Laboratory plus Clinical Monitoring (LCM)
Other
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Laboratory plus Clinical Monitoring (LCM)
Arm A: ABC+3TC+NNRTI
Drug
Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Arm A: abacavir (ABC)+lamivudine (3TC)+NNRTI
ABC: abacavir: Ziagen
3TC: lamivudine: Epivir
ABC+3TC co-formulated: Kivexa
NVP: nevirapine, Viramune
EFV: efavirenz, Sustiva
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI maintenance
Drug
Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI maintenance
ZDV: zidovudine, azidothymidine, Retrovir
ABC: abacavir: Ziagen
3TC: lamivudine: Epivir
ZDV+3TC co-formulated: Combivir
ABC+3TC co-formulated: Kivexa
ZDV+ABC+3TC co-formulated: Trizivir
NVP: nevirapine, Viramune
EFV: efavirenz, Sustiva
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC maintenance
Drug
Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC maintenance
ZDV: zidovudine, azidothymidine, Retrovir
ABC: abacavir: Ziagen
3TC: lamivudine: Epivir
ZDV+3TC co-formulated: Combivir
ABC+3TC co-formulated: Kivexa
ZDV+ABC+3TC co-formulated: Trizivir
NVP: nevirapine, Viramune
EFV: efavirenz, Sustiva
Once-daily ABC+3TC
Drug
Once-daily ABC+3TC
ABC: abacavir: Ziagen
3TC: lamivudine: Epivir
ABC+3TC co-formulated: Kivexa
Twice-daily ABC+3TC
Drug
Twice-daily ABC+3TC
ABC: abacavir: Ziagen
3TC: lamivudine: Epivir
ABC+3TC co-formulated: Kivexa
Continued cotrimoxazole prophylaxis
Drug
Continued cotrimoxazole prophylaxis
trimethoprim+sulfamethoxazole
Stopped cotrimoxazole prophylaxis
Other
Stopped cotrimoxazole prophylaxis
Number of participants with a new grade 3 or 4 adverse event (AE), not solely related to HIV, judged definitely/probably or uncertain whether related to lamivudine or abacavir, to be analysed using time-to-event methods
Median 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Cotrimoxazole: New Hospitalisation or Death
Number of participants with a new hospitalisation or death, to be analysed using time-to-event methods
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
Cotrimoxazole: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV
Number of participants with a new grade 3 or 4 adverse event (AE), not solely related to HIV, to be analysed using time-to-event methods
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
Number of participants with a new WHO stage 4 event or death, to be analysed using time-to-event methods
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
LCM vs CDM, Induction ART: New WHO Stage 3 or 4 Event or Death
Number of participants with a new WHO stage 3 or 4 event or death, to be analysed using time-to-event methods
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
LCM vs CDM, Induction ART: New or Recurrent WHO Stage 3 or 4 Event or Death
Number of participants with a new or recurrent WHO stage 3 or 4 event or death, to be analysed using time-to-event methods
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
LCM vs CDM, Induction ART: Weight-for-age Z-score
Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Baseline and a median of 4 years (maximum 5 years)
LCM vs CDM, Induction ART: Height-for-age Z-score
Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Baseline and a median of 4 years (maximum 5 years)
LCM vs CDM, Induction ART: Body Mass Index-for-age Z-score
Age-adjusted change in body mass index-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Baseline and a median of 4 years (maximum 5 years)
LCM vs CDM: Change From Baseline in CD4% to Week 72
Baseline, week 72
LCM vs CDM: Change From Baseline in CD4% to Week 144
Baseline, week 144
LCM vs CDM, Induction ART: Change From Baseline in Absolute CD4 to Week 72
Estimated in those >5 years at enrolment, in whom absolute CD4 is meaningful. (In uninfected children, CD4 decreases with age during early childhood.)
Baseline, week 72
LCM vs CDM, Induction ART: Change From Baseline in Absolute CD4 to Week 144
Estimated in those >5 years at enrolment, in whom absolute CD4 is meaningful. (In uninfected children, CD4 decreases with age during early childhood.)
Baseline, week 144
CDM vs LCM, Induction ART: Suppression of HIV RNA Viral Load 72 Weeks After Baseline
Number of participants with HIV RNA viral load <80 copies/ml 72 weeks after baseline. Threshold for suppression <80 copies/ml as samples had to be diluted due to low volumes.
72 weeks
CDM vs LCM, Induction ART: Suppression of HIV RNA Viral Load 144 Weeks After Baseline
Number of participants with HIV RNA viral load <80 copies/ml 144 weeks after baseline. Threshold for suppression <80 copies/ml as samples had to be diluted due to low volumes.
144 weeks
LCM vs CDM, Induction ART: Cessation of First-line Regimen for Clinical/Immunological Failure
Number of participants stopping their first-line regimen for clinical/immunological failure, to be analysed using time-to-event methods
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
LCM vs CDM, Induction ART: New Grade 3 or 4 Adverse Event Definitely/Probably or Uncertainly Related to ART
Number of participants with a new grade 3 or 4 adverse event definitely/probably or uncertainly related to ART, to be analysed using time-to-event methods
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
LCM vs CDM, Induction ART: New Serious Adverse Events Not Solely Related to HIV
Number of participants with a new serious adverse events not solely related to HIV, to be analysed using time-to-event methods
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
LCM vs CDM, Induction ART: New ART-modifying Adverse Event
Number of participants with a new ART-modifying adverse event, to be analysed using time-to-event methods
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
LCM vs CDM, Induction ART: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks)
Binary outcome measure: missed any doses of ART in the last 4 weeks by self-report. Mean calculated across all 12-weekly visits attended over the whole follow-up (no specific timepoint prespecified), giving the percentage of visits attended where the carer/participant reported missing any pills in the last 4 weeks.
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
Once Versus Twice Daily Abacavir+Lamivudine: Suppression of HIV RNA Viral Load 96 Weeks After Randomisation
Number of participants with HIV RNA viral load <80 copies/ml at 96 weeks. Threshold for suppression <80 copies/ml as samples had to be diluted due to low volumes.
96 weeks
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in CD4% to Week 48
Randomisation to once vs twice daily, week 48
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in CD4% to Week 72
Baseline, week 72
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in CD4% to Week 96
Randomisation to once vs twice daily, week 96
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in Absolute CD4 to Week 48
Estimated in those >5 years at enrolment, in whom absolute CD4 is meaningful. (In uninfected children, CD4 decreases with age during early childhood.)
Randomisation to once vs twice daily, week 48
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in Absolute CD4 to Week 72
All participants aged >5 years at randomization to once versus twice daily alive in follow-up with CD4 measured
Baseline, week 72
Once Versus Twice Daily Abacavir+Lamivudine: Change From Baseline in Absolute CD4 to Week 96
All participants aged >5 years at randomization to once versus twice daily alive in follow-up with CD4 measured
Randomisation to once vs twice daily, week 96
Once Versus Twice Daily Abacavir+Lamivudine: All-cause Mortality
Number of participants who died, to be analysed using time-to-event methods
Median 2 years (from randomization to 16 March 2012; maximum 2.6 years)
Once Versus Twice Daily Abacavir+Lamivudine: New WHO Stage 4 Event or Death
Number of participants with a new WHO stage 4 event or death, to be analysed using time-to-event methods
Median 2 years (from randomization to 16 March 2012; maximum 2.6 years)
Once Versus Twice Daily Abacavir+Lamivudine: New WHO Stage 3 or 4 Event or Death
Number of participants with a new WHO stage 3 or 4 event or death, to be analysed using time-to-event methods
Median 2 years (from randomization to 16 March 2012; maximum 2.6 years)
Once Versus Twice Daily Abacavir+Lamivudine: Height-for-age Z-score
Age-adjusted change in height-for-age Z-score over all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Baseline and a median of 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Once Versus Twice Daily Abacavir+Lamivudine: Weight-for-age Z-score
Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Baseline and a median of 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Once Versus Twice Daily Abacavir+Lamivudine: Body Mass Index-for-age Z-score
Age-adjusted change in body mass index-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Baseline and a median of 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Once Versus Twice Daily Abacavir+Lamivudine: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV
Number of participants with a new grade 3 or 4 adverse event (AE), not solely related to HIV, to be analysed using time-to-event methods
Median 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Once Versus Twice Daily Abacavir+Lamivudine: New Serious Adverse Events Not Solely Related to HIV
Number of participants with a new serious adverse event not solely related to HIV, to be analysed using time-to-event methods
Median 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Once Versus Twice Daily Abacavir+Lamivudine: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks) at 48 Weeks
Number of participants reporting missing any doses of ART in the last 4 weeks by self-report at 48 weeks.
48 weeks after randomization to once- versus twice-daily
Once Versus Twice Daily Abacavir+Lamivudine: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks) at 96 Weeks
Number of participants reporting missing any doses of ART in the last 4 weeks by self-report at 96 weeks.
96 weeks after randomization to once- versus twice-daily
Once Versus Twice Daily Abacavir+Lamivudine: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks)
Binary outcome measure: missed any doses of ART in the last 4 weeks by self-report. Mean calculated across all 12-weekly visits attended over the whole follow-up (no specific timepoint prespecified), giving the percentage of visits attended where the carer/participant reported missing any pills in the last 4 weeks.
Mean over median 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Cotrimoxazole: New Clinical and Diagnostic Positive Malaria
Number of participants with a new clinical and diagnostic positive malaria, to be analysed using time-to-event methods. Diagnostic positive by either microscopy (thick film) or rapid diagnostic test (RDT)
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
Cotrimoxazole: New Severe Pneumonia
Number of participants with a new severe pneumonia, to be analysed using time-to-event methods
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
Cotrimoxazole: New WHO Stage 3 or 4 Event or Death
Number of participants with a new WHO stage 3 or 4 event or death, to be analysed using time-to-event methods
Median 2 years (from randomization to 16 March 2012; maximum 2.5 years)
Cotrimoxazole: New WHO Stage 3 Severe Recurrent Pneumonia or Diarrhoea
Number of participants with a new WHO stage 3 severe recurrent pneumonia or diarrhoea, to be analysed using time-to-event methods
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
Cotrimoxazole: New WHO Stage 4 Event or Death
Number of participants with a new WHO stage 4 event or death, to be analysed using time-to-event methods
Median 2 years (from randomization to 16 March 2012; maximum 2.5 years)
Cotrimoxazole: All-cause Mortality
Number of participants who died, to be analysed using time-to-event methods
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
Cotrimoxazole: Weight-for-age Z-score
Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Baseline and a median of 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
Cotrimoxazole: Height-for-age Z-score
Age-adjusted change in height-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Baseline and a median of 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
Cotrimoxazole: Body Mass Index-for-age Z-score
Age-adjusted change in body mass index-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Baseline and a median of 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
Cotrimoxazole: Change From Baseline in CD4% to Week 72
Baseline, week 72
Cotrimoxazole: Change From Baseline in Absolute CD4 to Week 72
Estimated in those >5 years at randomization to stop vs continue, in whom absolute CD4 is meaningful. (In uninfected children, CD4 decreases with age during early childhood.)
Baseline, week 72
Cotrimoxazole: New Serious Adverse Events Not Solely Related to HIV
Number of participants with a new serious adverse event not solely related to HIV, to be analysed using time-to-event methods
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
Cotrimoxazole: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks)
Binary outcome measure: missed any doses of ART in the last 4 weeks by self-report. Mean calculated across all 12-weekly visits attended over the whole follow-up (no specific timepoint prespecified), giving the percentage of visits attended where the carer/participant reported missing any pills in the last 4 weeks.
Mean over median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
Principal Investigator
Patricia Nahirya-Ntege, MBChB
MRC/UVRI and LSHTM Uganda Research Unit
Principal Investigator
Kampala
Uganda
Baylor College of Medicine Children's Foundation
Mulago
Uganda
University of Zimbabwe Medical School
Harare
Zimbabwe
Bwakura-Dangarembizi M, Kendall L, Bakeera-Kitaka S, Nahirya-Ntege P, Keishanyu R, Nathoo K, Spyer MJ, Kekitiinwa A, Lutaakome J, Mhute T, Kasirye P, Munderi P, Musiime V, Gibb DM, Walker AS, Prendergast AJ. A randomized trial of prolonged co-trimoxazole in HIV-infected children in Africa. N Engl J Med. 2014 Jan 2;370(1):41-53. doi: 10.1056/NEJMoa1214901.
Musiime V, Kasirye P, Naidoo-James B, Nahirya-Ntege P, Mhute T, Cook A, Mugarura L, Munjoma M, Thoofer NK, Ndashimye E, Nankya I, Spyer MJ, Thomason MJ, Snowden W, Gibb DM, Walker AS; ARROW Trial Team. Once vs twice-daily abacavir and lamivudine in African children. AIDS. 2016 Jul 17;30(11):1761-70. doi: 10.1097/QAD.0000000000001116.
FG001
Laboratory Plus Clinical Monitoring (LCM)
Laboratory plus Clinical Monitoring (LCM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
FG002
Arm A: Abacavir (ABC)+Lamivudine (3TC)+NNRTI
ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO non-nucleoside reverse transcriptase inhibitor (NNRTI): either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm A: ABC+3TC+NNRTI: Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
FG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
ZDV [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
FG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
ZDV [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
FG005
Once-daily ABC+3TC
ABC [abacavir]: syrup or tablet, dosed once-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed once-daily according to weight-bands following WHO
Once-daily ABC+3TC
FG006
Twice-daily ABC+3TC
ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO
Children had been taking once-daily cotrimoxazole prophylaxis since at least ART initiation. Children randomised to this experimental arm stopped taking cotrimoxazole prophylaxis.
Stopped cotrimoxazole prophylaxis
FG000606 subjectsFactorial randomization at enrolment: Number of eligible children randomized to this group in ARROW
FG001600 subjectsFactorial randomization at enrolment: Number of eligible children randomized to this group in ARROW
FG0020 subjectsFactorial randomization at enrolment: Number of eligible children randomized to this group in ARROW
FG0030 subjectsFactorial randomization at enrolment: Number of eligible children randomized to this group in ARROW
FG0040 subjectsFactorial randomization at enrolment: Number of eligible children randomized to this group in ARROW
FG0050 subjectsSecondary partial factorial randomization: Only a subset of ARROW children were eligible
FG0060 subjectsSecondary partial factorial randomization: Only a subset of ARROW children were eligible
FG0070 subjectsSecondary partial factorial randomization: Only a subset of ARROW children were eligible
FG0080 subjectsSecondary partial factorial randomization: Only a subset of ARROW children were eligible
COMPLETED
FG000606 subjects
FG001600 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
Initial Enrolment: Induction ART
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG002397 subjects
FG003404 subjects
FG004405 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG002397 subjects
FG003404 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Subsequent Once vs Twice Daily ABC+3TC
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG005336 subjects
FG006333 subjects
FG0070 subjects
FG0080 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Subsequent Cotrimoxazole Randomization
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG007376 subjects
FG008382 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
All participants who were randomized were included except those who were randomised in error (main enrollment: 1 child HIV-uninfected, 2 on main phase of tuberculosis treatment; cotrimoxazole secondary randomization: 2 children receiving dapsone prophylaxis not cotrimoxazole).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Clinically Driven Monitoring (CDM)
Clinically Driven Monitoring (CDM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
BG001
Laboratory Plus Clinical Monitoring (LCM)
Laboratory plus Clinical Monitoring (LCM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
BG002
Arm A: Abacavir (ABC)+Lamivudine (3TC)+NNRTI
ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO non-nucleoside reverse transcriptase inhibitor (NNRTI): either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm A: ABC+3TC+NNRTI: Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
BG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
ZDV [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
BG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
ZDV [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
BG005
Once-daily ABC+3TC
ABC [abacavir]: syrup or tablet, dosed once-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed once-daily according to weight-bands following WHO
Once-daily ABC+3TC
BG006
Twice-daily ABC+3TC
ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO
Children had been taking once-daily cotrimoxazole prophylaxis since at least ART initiation. Children randomised to this experimental arm stopped taking cotrimoxazole prophylaxis.
Stopped cotrimoxazole prophylaxis
BG009
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000606
BG001600
BG002397
BG003404
BG004405
BG005336
BG006333
BG007376
BG008382
BG0093839
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Age at trial enrollment (antiretroviral therapy initiation).
Median
Inter-Quartile Range
years
Title
Denominators
Categories
Title
Measurements
BG0005.9(2.2 to 9.2)
BG0016.0(2.6 to 9.4)
BG002NA(NA to NA)Different randomized comparison
Age, Customized
Age at trial enrollment (antiretroviral therapy initiation).
Number
participants
Title
Denominators
Categories
< 3 years
Title
Measurements
BG000197
BG001173
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG000308
BG001302
BG002
Region of Enrollment
Region of enrollment at trial enrollment (antiretroviral therapy initiation).
Number
participants
Title
Denominators
Categories
Uganda
Title
Measurements
BG000405
BG001401
BG002
Age, continuous: Period 2 (trial enrollment, induction ART)
Age at trial enrollment (antiretroviral therapy initiation).
Median
Inter-Quartile Range
years
Title
Denominators
Categories
Title
Measurements
BG000NA(NA to NA)Different randomized comparison
BG001
Age, continuous: Period 3 (randomization to once vs twice daily ABC+3TC)
Age at the time of the secondary randomization to once versus twice daily abacavir+lamivudine (in those children eligible and randomized).
Median
Inter-Quartile Range
years
Title
Denominators
Categories
Title
Measurements
BG000NA(NA to NA)Different randomized comparison
BG001
Age, continuous: Period 4 (randomization to stop versus continue cotrimoxazole)
Age at the time of the secondary randomization to stop versus continue cotrimoxazole prophylaxis (in those children eligible and randomized).
Median
Inter-Quartile Range
years
Title
Denominators
Categories
Title
Measurements
BG000NA(NA to NA)Different randomized comparison
BG001
Age, categorical: Period 2 (trial enrollment, induction ART)
Number
participants
Title
Denominators
Categories
<3 years
Title
Measurements
BG000NADifferent randomized comparison
BG001NADifferent randomized comparison
BG002
Age, categorical: Period 3 (randomization to once vs twice daily ABC+3TC)
Number
participants
Title
Denominators
Categories
<3 years
Title
Measurements
BG000NADifferent randomized comparison
BG001NADifferent randomized comparison
BG002
Age, categorical: Period 4 (randomization to stop versus continue cotrimoxazole)
Number
participants
Title
Denominators
Categories
<3 years
Title
Measurements
BG000NADifferent randomized comparison
BG001NADifferent randomized comparison
BG002
Gender, Male/Female: Period 2 (trial enrollment, induction ART)
Number
participants
Title
Denominators
Categories
Female
Title
Measurements
BG000NADifferent randomized comparison
BG001NADifferent randomized comparison
BG002
Gender, Male/Female: Period 3 (randomization to once vs twice daily ABC+3TC)
Number
participants
Title
Denominators
Categories
Female
Title
Measurements
BG000NADifferent randomized comparison
BG001NADifferent randomized comparison
BG002
Gender, Male/Female: Period 4 (randomization to stop versus continue cotrimoxazole)
Number
participants
Title
Denominators
Categories
Female
Title
Measurements
BG000NADifferent randomized comparison
BG001NADifferent randomized comparison
BG002
Region of Enrollment: Period 2 (trial enrollment, induction ART)
Number
participants
Title
Denominators
Categories
Uganda
Title
Measurements
BG000NADifferent randomized comparison
BG001NADifferent randomized comparison
BG002
Region of Enrollment: Period 3 (randomization to once vs twice daily ABC+3TC)
Number
participants
Title
Denominators
Categories
Uganda
Title
Measurements
BG000NADifferent randomized comparison
BG001NADifferent randomized comparison
BG002
Region of Enrollment: Period 4 (randomization to stop versus continue cotrimoxazole)
Number
participants
Title
Denominators
Categories
Uganda
Title
Measurements
BG000NADifferent randomized comparison
BG001NADifferent randomized comparison
BG002
CD4 T cell percentage
CD4 T cell percentage at trial enrollment (antiretroviral therapy initiation).
Median
Inter-Quartile Range
percentage of total lymphocytes
Title
Denominators
Categories
Title
Measurements
BG00012.5(7.5 to 17.3)
BG00112.0(7.0 to 17.0)
CD4 T cell percentage: Period 2 (trial enrollment, induction ART)
CD4 T cell percentage at trial enrollment (antiretroviral therapy initiation).
Median
Inter-Quartile Range
percentage of total lymphocytes
Title
Denominators
Categories
Title
Measurements
BG000NA(NA to NA)Different randomized comparison
BG001
CD4 T cell percentage: Period 3 (randomization to once vs twice daily ABC+3TC)
CD4 T cell percentage at the time of the secondary randomization to once versus twice daily abacavir+lamivudine (in those children eligible and randomized).
Median
Inter-Quartile Range
percentage of total lymphocytes
Title
Denominators
Categories
Title
Measurements
BG000NA(NA to NA)Different randomized comparison
BG001
CD4 T cell percentage: Period 4 (randomization to stop versus continue cotrimoxazole)
CD4 T cell percentage at the time of the secondary randomization to stop versus continue cotrimoxazole prophylaxis (in those children eligible and randomized).
Median
Inter-Quartile Range
percentage of total lymphocytes
Title
Denominators
Categories
Title
Measurements
BG000NA(NA to NA)Different randomized comparison
BG001
Duration of antiretroviral therapy: Period 3 (randomization to once vs twice daily ABC+3TC)
Years on antiretroviral therapy at the time of the secondary randomization to once versus twice daily abacavir+lamivudine (in those children eligible and randomized).
Median
Full Range
years
Title
Denominators
Categories
Title
Measurements
BG000NA(NA to NA)Different randomized comparison
BG001
Duration of antiretroviral therapy: Period 4 (randomization to stop versus continue cotrimoxazole)
Years on antiretroviral therapy at the time of the secondary randomization to stop versus continue cotrimoxazole prophylaxis (in those children eligible and randomized).
Median
Full Range
years
Title
Denominators
Categories
Title
Measurements
BG000NA(NA to NA)Different randomized comparison
BG001
Weight-for-age Z-score: Period 1 (trial enrollment, CDM vs LCM)
Weight-for-age Z-score at trial enrollment (antiretroviral therapy initiation).
Median
Inter-Quartile Range
Z-score
Title
Denominators
Categories
Title
Measurements
BG000-2.3(-3.4 to -1.3)
BG001-2.2
Weight-for-age Z-score: Period 2 (trial enrollment, induction ART)
Weight-for-age Z-score at trial enrollment (antiretroviral therapy initiation).
Median
Inter-Quartile Range
Z-score
Title
Denominators
Categories
Title
Measurements
BG000NA(NA to NA)Different randomized comparison
BG001
Weight-for-age Z-score: Period 3 (randomization to once vs twice daily ABC+3TC)
Weight-for-age Z-score at the time of the secondary randomization to once versus twice daily abacavir+lamivudine (in those children eligible and randomized).
Median
Inter-Quartile Range
Z-score
Title
Denominators
Categories
Title
Measurements
BG000NA(NA to NA)Different randomized comparison
BG001
Weight-for-age Z-score: Period 4 (randomization to stop versus continue cotrimoxazole)
Weight-for-age Z-score at the time of the secondary randomization to stop versus continue cotrimoxazole prophylaxis (in those children eligible and randomized).
Median
Inter-Quartile Range
Z-score
Title
Denominators
Categories
Title
Measurements
BG000NA(NA to NA)Different randomized comparison
BG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
LCM vs CDM: Disease Progression to a New WHO Stage 4 Event or Death
Number of participants with disease progression to a new WHO stage 4 event or death, to be analysed using time-to-event methods
All randomized participants (time-to-event)
Posted
Number
participants
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Units
Counts
Participants
OG000606
OG001600
Title
Denominators
Categories
Title
Measurements
OG00047
OG00139
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.59
Hazard Ratio (HR)
1.13
2-Sided
95
0.73
1.73
Hazard ratio is CDM vs LCM
Yes
Non-Inferiority or Equivalence
Upper 95% confidence interval for the hazard ratio was 1.64, see other analysis for this endpoint for details
Primary
LCM vs CDM: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV
Number of participants with a new Grade 3 or 4 adverse event (AE), not solely related to HIV, to be analysed using time-to-event methods
Posted
Number
participants
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Primary
Induction ART: Change From Baseline in CD4% 72 Weeks After ART Initiation
All participants alive at 72 weeks with CD4 measured (completeness in those in follow-up was 96.6%).
Posted
Mean
Standard Error
percentage of total lymphocytes
Baseline, 72 weeks
ID
Title
Description
OG000
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG001
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG002
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Primary
Induction ART: Change From Baseline in CD4% to 144 Weeks From ART Initiation
All participants alive in follow-up with CD4% (95% completeness)
Posted
Mean
Standard Error
percentage of total lymphocytes
Baseline, 144 weeks
ID
Title
Description
OG000
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG001
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG002
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Primary
Induction ART: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV
Number of participants with a new grade 3 or 4 adverse event (AE), not solely related to HIV, to be analysed using time-to-event methods
Posted
Number
participants
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG001
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG002
ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Primary
Once Versus Twice Daily Abacavir+Lamivudine: Suppressed HIV RNA Viral Load 48 Weeks After Randomisation
Number of participants with HIV RNA viral load <80 copies/ml at 48 weeks. Measured retrospectively on stored plasma specimens: due to low stored volumes from some children, samples had to be diluted and therefore a threshold of <80 copies/ml was used to indicate suppression.
All randomized participants with VL result from stored plasma specimen (available for 661/669, 99%, randomized participants)
Once Versus Twice Daily Abacavir+Lamivudine: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV, Judged Definitely/Probably or Uncertain Whether Related to Lamivudine or Abacavir
Number of participants with a new grade 3 or 4 adverse event (AE), not solely related to HIV, judged definitely/probably or uncertain whether related to lamivudine or abacavir, to be analysed using time-to-event methods
Posted
Number
participants
Median 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Number of participants with a new hospitalisation or death, to be analysed using time-to-event methods
Posted
Number
participants
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Primary
Cotrimoxazole: New Grade 3 or 4 Adverse Event (AE), Not Solely Related to HIV
Number of participants with a new grade 3 or 4 adverse event (AE), not solely related to HIV, to be analysed using time-to-event methods
Posted
Number
participants
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
LCM vs CDM, Induction ART: All-cause Mortality
Number of participants who died from any cause, to be analysed using time-to-event methods
Posted
Number
participants
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
Induction ART: New WHO Stage 4 Event or Death
Number of participants with a new WHO stage 4 event or death, to be analysed using time-to-event methods
Posted
Number
participants
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG001
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG002
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Secondary
LCM vs CDM, Induction ART: New WHO Stage 3 or 4 Event or Death
Number of participants with a new WHO stage 3 or 4 event or death, to be analysed using time-to-event methods
Posted
Number
participants
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM, Induction ART: New or Recurrent WHO Stage 3 or 4 Event or Death
Number of participants with a new or recurrent WHO stage 3 or 4 event or death, to be analysed using time-to-event methods
Posted
Number
participants
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM, Induction ART: Weight-for-age Z-score
Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Posted
Mean
Standard Deviation
age-adjusted z-score
Baseline and a median of 4 years (maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM, Induction ART: Height-for-age Z-score
Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Posted
Mean
Standard Deviation
age-adjusted z-score
Baseline and a median of 4 years (maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM, Induction ART: Body Mass Index-for-age Z-score
Age-adjusted change in body mass index-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Posted
Mean
Standard Deviation
age-adjusted z-score
Baseline and a median of 4 years (maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM: Change From Baseline in CD4% to Week 72
All participants alive in follow-up with CD4% (97% completeness)
Posted
Mean
Standard Error
percentage of total lymphocytes
Baseline, week 72
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM: Change From Baseline in CD4% to Week 144
All participants alive in follow-up with CD4% (95% completeness)
Posted
Mean
Standard Error
percentage of total lymphocytes
Baseline, week 144
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM, Induction ART: Change From Baseline in Absolute CD4 to Week 72
Estimated in those >5 years at enrolment, in whom absolute CD4 is meaningful. (In uninfected children, CD4 decreases with age during early childhood.)
All participants alive in follow-up with CD4
Posted
Mean
Standard Error
absolute cells per mm3
Baseline, week 72
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM, Induction ART: Change From Baseline in Absolute CD4 to Week 144
Estimated in those >5 years at enrolment, in whom absolute CD4 is meaningful. (In uninfected children, CD4 decreases with age during early childhood.)
All participants alive in follow-up with CD4
Posted
Mean
Standard Error
absolute cells per mm3
Baseline, week 144
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
CDM vs LCM, Induction ART: Suppression of HIV RNA Viral Load 72 Weeks After Baseline
Number of participants with HIV RNA viral load <80 copies/ml 72 weeks after baseline. Threshold for suppression <80 copies/ml as samples had to be diluted due to low volumes.
Viral loads were assayed retrospectively in a random subset of children
Posted
Number
participants
72 weeks
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Secondary
CDM vs LCM, Induction ART: Suppression of HIV RNA Viral Load 144 Weeks After Baseline
Number of participants with HIV RNA viral load <80 copies/ml 144 weeks after baseline. Threshold for suppression <80 copies/ml as samples had to be diluted due to low volumes.
Viral load was assayed retrospectively at week 144 on a random subset of participants, plus all those aged <5 years at enrolment
Posted
Number
participants
144 weeks
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Secondary
LCM vs CDM, Induction ART: Cessation of First-line Regimen for Clinical/Immunological Failure
Number of participants stopping their first-line regimen for clinical/immunological failure, to be analysed using time-to-event methods
Posted
Number
participants
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM, Induction ART: New Grade 3 or 4 Adverse Event Definitely/Probably or Uncertainly Related to ART
Number of participants with a new grade 3 or 4 adverse event definitely/probably or uncertainly related to ART, to be analysed using time-to-event methods
Posted
Number
participants
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM, Induction ART: New Serious Adverse Events Not Solely Related to HIV
Number of participants with a new serious adverse events not solely related to HIV, to be analysed using time-to-event methods
Posted
Number
participants
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM, Induction ART: New ART-modifying Adverse Event
Number of participants with a new ART-modifying adverse event, to be analysed using time-to-event methods
Posted
Number
participants
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
Secondary
LCM vs CDM, Induction ART: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks)
Binary outcome measure: missed any doses of ART in the last 4 weeks by self-report. Mean calculated across all 12-weekly visits attended over the whole follow-up (no specific timepoint prespecified), giving the percentage of visits attended where the carer/participant reported missing any pills in the last 4 weeks.
Posted
Mean
Standard Deviation
% of visits reporting missed pills
Median 4 years (from randomization to 16 March 2012; maximum 5 years)
ID
Title
Description
OG000
Clinically Driven Monitoring (CDM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results at and after randomisation were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG001
Secondary
Once Versus Twice Daily Abacavir+Lamivudine: Suppression of HIV RNA Viral Load 96 Weeks After Randomisation
Number of participants with HIV RNA viral load <80 copies/ml at 96 weeks. Threshold for suppression <80 copies/ml as samples had to be diluted due to low volumes.
All participants with viral load assayed in stored specimens (98% of those randomized)
Once Versus Twice Daily Abacavir+Lamivudine: Height-for-age Z-score
Age-adjusted change in height-for-age Z-score over all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Posted
Mean
Standard Deviation
age-adjusted z-score
Baseline and a median of 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Once Versus Twice Daily Abacavir+Lamivudine: Weight-for-age Z-score
Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Posted
Mean
Standard Deviation
age-adjusted z-score
Baseline and a median of 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Once Versus Twice Daily Abacavir+Lamivudine: Body Mass Index-for-age Z-score
Age-adjusted change in body mass index-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Posted
Mean
Standard Deviation
age-adjusted z-score
Baseline and a median of 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Once Versus Twice Daily Abacavir+Lamivudine: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks) at 48 Weeks
Number of participants reporting missing any doses of ART in the last 4 weeks by self-report at 48 weeks.
All participants completing the questionnaire
Posted
Number
participants
48 weeks after randomization to once- versus twice-daily
Once Versus Twice Daily Abacavir+Lamivudine: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks) at 96 Weeks
Number of participants reporting missing any doses of ART in the last 4 weeks by self-report at 96 weeks.
All participants completing the questionnaire
Posted
Number
participants
96 weeks after randomization to once- versus twice-daily
Once Versus Twice Daily Abacavir+Lamivudine: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks)
Binary outcome measure: missed any doses of ART in the last 4 weeks by self-report. Mean calculated across all 12-weekly visits attended over the whole follow-up (no specific timepoint prespecified), giving the percentage of visits attended where the carer/participant reported missing any pills in the last 4 weeks.
Posted
Mean
Standard Deviation
% of visits reporting missed pills
Mean over median 2 years (from once vs twice daily randomization to 16 March 2012; maximum 2.6 years)
Cotrimoxazole: New Clinical and Diagnostic Positive Malaria
Number of participants with a new clinical and diagnostic positive malaria, to be analysed using time-to-event methods. Diagnostic positive by either microscopy (thick film) or rapid diagnostic test (RDT)
Posted
Number
participants
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
Cotrimoxazole: New Severe Pneumonia
Number of participants with a new severe pneumonia, to be analysed using time-to-event methods
Posted
Number
participants
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
Cotrimoxazole: New WHO Stage 3 or 4 Event or Death
Number of participants with a new WHO stage 3 or 4 event or death, to be analysed using time-to-event methods
Posted
Number
participants
Median 2 years (from randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
Cotrimoxazole: New WHO Stage 3 Severe Recurrent Pneumonia or Diarrhoea
Number of participants with a new WHO stage 3 severe recurrent pneumonia or diarrhoea, to be analysed using time-to-event methods
Posted
Number
participants
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
Cotrimoxazole: New WHO Stage 4 Event or Death
Number of participants with a new WHO stage 4 event or death, to be analysed using time-to-event methods
Posted
Number
participants
Median 2 years (from randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
Cotrimoxazole: All-cause Mortality
Number of participants who died, to be analysed using time-to-event methods
Posted
Number
participants
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
Cotrimoxazole: Weight-for-age Z-score
Age-adjusted change in weight-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Posted
Mean
Standard Deviation
age-adjusted z-score
Baseline and a median of 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
Cotrimoxazole: Height-for-age Z-score
Age-adjusted change in height-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Posted
Mean
Standard Deviation
age-adjusted z-score
Baseline and a median of 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
Cotrimoxazole: Body Mass Index-for-age Z-score
Age-adjusted change in body mass index-for-age Z-score at all 12-weekly visits attended over the whole follow-up, no specific timepoint prespecified. Mean and SD are time-averaged area under the change curve calculated using the trapezoidal rule. Z-scores calculated using UK norms which cover the full age range of children (Cole, T. J., J. V. Freeman, and M. A. Preece. 1998. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Statistics in Medicine 17(4): 407-29).
Posted
Mean
Standard Deviation
age-adjusted z-score
Baseline and a median of 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
Cotrimoxazole: Change From Baseline in CD4% to Week 72
All participants alive in follow-up with CD4%
Posted
Mean
Standard Deviation
percentage of total lymphocytes
Baseline, week 72
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000360
Secondary
Cotrimoxazole: Change From Baseline in Absolute CD4 to Week 72
Estimated in those >5 years at randomization to stop vs continue, in whom absolute CD4 is meaningful. (In uninfected children, CD4 decreases with age during early childhood.)
All participants aged >5 years at randomization to stop versus continue alive in follow-up with CD4 measured
Posted
Mean
Standard Deviation
cells per mm3
Baseline, week 72
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
Cotrimoxazole: New Serious Adverse Events Not Solely Related to HIV
Number of participants with a new serious adverse event not solely related to HIV, to be analysed using time-to-event methods
Posted
Number
participants
Median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Secondary
Cotrimoxazole: Adherence to ART as Measured by Self-reported Questionnaire (Missing Any Pills in the Last 4 Weeks)
Binary outcome measure: missed any doses of ART in the last 4 weeks by self-report. Mean calculated across all 12-weekly visits attended over the whole follow-up (no specific timepoint prespecified), giving the percentage of visits attended where the carer/participant reported missing any pills in the last 4 weeks.
Posted
Mean
Standard Deviation
% of visits reporting missed pills
Mean over median 2 years (from cotrimoxazole randomization to 16 March 2012; maximum 2.5 years)
ID
Title
Description
OG000
Continued Cotrimoxazole Prophylaxis
Other Names:
trimethoprim+sulfamethoxazole
OG001
Stopped Cotrimoxazole Prophylaxis
Units
Counts
Participants
OG000
Time Frame
LCM vs CDM and induction-maintenance: median 4 years (maximum 5 years); for randomizations; once vs twice daily: median 2 years (maximum 2.6 years); cotrimoxazole: median 2 years (maximum 2.5 years)
Description
Children were reviewed by a doctor at every scheduled doctor visit, as well as additional visits, and prompts on the doctor follow-up CRF asked about new/worsening/resolved Serious Adverse Events and Grade 3 or 4 Adverse Events.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Clinically Driven Monitoring (CDM)
Clinically Driven Monitoring (CDM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. Screening results were used to assess eligibility. All subsequent results were only returned if requested for clinical management (authorised by centre project leaders); haemoglobin results at week 8 were automatically returned on the basis of early anaemia in a previous adult trial as were grade 4 laboratory toxicities (protocol safety criteria). Total lymphocytes and CD4 tests were never returned for CDM participants, but for all children other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
147
606
190
606
EG001
Laboratory Plus Clinical Monitoring (LCM)
Laboratory plus Clinical Monitoring (LCM): Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
117
600
198
600
EG002
Arm A: Abacavir (ABC)+Lamivudine (3TC)+NNRTI
ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO non-nucleoside reverse transcriptase inhibitor (NNRTI): either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm A: ABC+3TC+NNRTI: Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
87
397
96
397
EG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
ZDV [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
92
404
124
404
EG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
ZDV [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO NNRTI: either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC maintenance: Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
95
405
168
405
EG005
Once-daily ABC+3TC
ABC [abacavir]: syrup or tablet, dosed once-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed once-daily according to weight-bands following WHO
Once-daily ABC+3TC
30
336
33
336
EG006
Twice-daily ABC+3TC
ABC [abacavir]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC [lamivudine]: syrup or tablet, dosed twice-daily according to weight-bands following WHO
Children had been taking once-daily cotrimoxazole prophylaxis since at least ART initiation. Children randomised to this experimental arm stopped taking cotrimoxazole prophylaxis.
Stopped cotrimoxazole prophylaxis
48
382
26
382
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Coma
Nervous system disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0021 events1 affected397 at risk
EG0030 events0 affected404 at risk
EG0040 events0 affected405 at risk
EG0051 events1 affected336 at risk
EG0060 events0 affected333 at risk
EG0070 events0 affected376 at risk
EG0081 events1 affected382 at risk
Acute diarrhoea
Gastrointestinal disorders
Trial-specific
Systematic Assessment
EG00010 events10 affected606 at risk
EG0016 events6 affected600 at risk
EG0024 events4 affected397 at risk
EG003
Hyperthyroidism
Endocrine disorders
Trial-specific
Systematic Assessment
EG0000 events0 affected606 at risk
EG0011 events1 affected600 at risk
EG0021 events1 affected397 at risk
EG003
Gasteroenteritis
Gastrointestinal disorders
Trial-specific
Systematic Assessment
EG0003 events3 affected606 at risk
EG0012 events2 affected600 at risk
EG0021 events1 affected397 at risk
EG003
Vomiting
Gastrointestinal disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0021 events1 affected397 at risk
EG003
Clinical Anaemia
Blood and lymphatic system disorders
Trial-specific
Systematic Assessment
EG00018 events17 affected606 at risk
EG00112 events12 affected600 at risk
EG0026 events6 affected397 at risk
EG003
Bronchietasis
Respiratory, thoracic and mediastinal disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Pneumonia
Respiratory, thoracic and mediastinal disorders
Trial-specific
Systematic Assessment
EG0007 events7 affected606 at risk
EG0017 events7 affected600 at risk
EG0026 events6 affected397 at risk
EG003
Bone fracture
Musculoskeletal and connective tissue disorders
Trial-specific
Systematic Assessment
EG0005 events5 affected606 at risk
EG0014 events4 affected600 at risk
EG0022 events2 affected397 at risk
EG003
Manic psychosis
Psychiatric disorders
Trial-specific
Systematic Assessment
EG0000 events0 affected606 at risk
EG0011 events1 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Trauma
Musculoskeletal and connective tissue disorders
Trial-specific
Systematic Assessment
EG0004 events4 affected606 at risk
EG0014 events4 affected600 at risk
EG0023 events3 affected397 at risk
EG003
Hypersensitivity reaction
Skin and subcutaneous tissue disorders
Trial-specific
Systematic Assessment
EG00022 events22 affected606 at risk
EG00119 events19 affected600 at risk
EG00215 events15 affected397 at risk
EG003
Measles
Infections and infestations
Trial-specific
Systematic Assessment
EG0007 events7 affected606 at risk
EG0014 events4 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Malaria
Infections and infestations
Trial-specific
Systematic Assessment
EG000113 events78 affected606 at risk
EG00165 events49 affected600 at risk
EG00269 events48 affected397 at risk
EG003
Septicaemia/bacteremia (presumptive)
Infections and infestations
Trial-specific
Systematic Assessment
EG0005 events5 affected606 at risk
EG0016 events5 affected600 at risk
EG0025 events4 affected397 at risk
EG003
Raised liver enzymes
Investigations
Trial-specific
Systematic Assessment
EG0000 events0 affected606 at risk
EG0011 events1 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Hypertension
Cardiac disorders
Trial-specific
Systematic Assessment
EG0002 events2 affected606 at risk
EG0010 events0 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Chronic diarrhoea
Gastrointestinal disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
Trial-specific
Systematic Assessment
EG0002 events2 affected606 at risk
EG0013 events3 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Pancytopenia
Blood and lymphatic system disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Acute hepatitis
Hepatobiliary disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0013 events3 affected600 at risk
EG0022 events2 affected397 at risk
EG003
Bronchospasm/asthma
Respiratory, thoracic and mediastinal disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0021 events1 affected397 at risk
EG003
Arthralgia/arthritis
Musculoskeletal and connective tissue disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Death, cause unknown
Nervous system disorders
Trial-specific
Systematic Assessment
Death at home with no further information available
EG0002 events2 affected606 at risk
EG0013 events3 affected600 at risk
EG0023 events3 affected397 at risk
EG003
Overdose
Psychiatric disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Pre-eclampsia
Pregnancy, puerperium and perinatal conditions
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Burns
Skin and subcutaneous tissue disorders
Trial-specific
Systematic Assessment
EG0000 events0 affected606 at risk
EG0011 events1 affected600 at risk
EG0021 events1 affected397 at risk
EG003
Maculopapular rash
Skin and subcutaneous tissue disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0011 events1 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Pneumococcal septicaemia
Blood and lymphatic system disorders
Trial-specific
Systematic Assessment
EG0002 events2 affected606 at risk
EG0010 events0 affected600 at risk
EG0021 events1 affected397 at risk
EG003
Kwashiorkor
Metabolism and nutrition disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Malnutrition
Metabolism and nutrition disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0021 events1 affected397 at risk
EG003
Febrile convulsions
Infections and infestations
Trial-specific
Systematic Assessment
EG0000 events0 affected606 at risk
EG0011 events1 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Chronic sinusitis
Respiratory, thoracic and mediastinal disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0010 events0 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Upper respiratory tract infection
Respiratory, thoracic and mediastinal disorders
Trial-specific
Systematic Assessment
EG0001 events1 affected606 at risk
EG0011 events1 affected600 at risk
EG0020 events0 affected397 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia with no clinical symptoms
Infections and infestations
Trial-specific
Systematic Assessment
EG00032 events29 affected606 at risk
EG00141 events37 affected600 at risk
EG00222 events20 affected397 at risk
EG00326 events22 affected404 at risk
EG004
Neutropenia with no clinical symptoms
Investigations
Trial-specific
Systematic Assessment
EG000211 events151 affected606 at risk
EG001206 events160 affected600 at risk
EG00292 events69 affected397 at risk
EG003
Thrombocytopenia with no clinical symptoms
Investigations
Trial-specific
Systematic Assessment
EG00044 events32 affected606 at risk
EG00129 events21 affected600 at risk
EG00224 events19 affected397 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
Not provided
Results Disclosure Restriction on PI(s)?
No
Other Details
Not provided
Point of Contact
Title
Organization
Phone
Extension
Email
Professor Ann Sarah Walker
Medical Research Council
+44 20 7670 4726
rmjlasw@ucl.ac.uk
ID
Term
D000163
Acquired Immunodeficiency Syndrome
Ancestor Terms
ID
Term
D015658
HIV Infections
D000086982
Blood-Borne Infections
D003141
Communicable Diseases
D007239
Infections
D015229
Sexually Transmitted Diseases, Viral
D012749
Sexually Transmitted Diseases
D016180
Lentivirus Infections
D012192
Retroviridae Infections
D012327
RNA Virus Infections
D014777
Virus Diseases
D012897
Slow Virus Diseases
D000091662
Genital Diseases
D000091642
Urogenital Diseases
D007153
Immunologic Deficiency Syndromes
D007154
Immune System Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D007753
Laboratories
D019829
Nevirapine
C098320
efavirenz
D015215
Zidovudine
D015662
Trimethoprim, Sulfamethoxazole Drug Combination
Ancestor Terms
ID
Term
D000072182
Non-Medical Public and Private Facilities
D006268
Health Facilities
D005159
Health Care Facilities Workforce and Services
D011725
Pyridines
D006573
Heterocyclic Compounds, 1-Ring
D006571
Heterocyclic Compounds
D013936
Thymidine
D011741
Pyrimidine Nucleosides
D011743
Pyrimidines
D015224
Dideoxynucleosides
D003853
Deoxyribonucleosides
D009705
Nucleosides
D009706
Nucleic Acids, Nucleotides, and Nucleosides
D013420
Sulfamethoxazole
D000096926
Benzenesulfonamides
D013449
Sulfonamides
D000577
Amides
D009930
Organic Chemicals
D013424
Sulfanilamides
D000814
Aniline Compounds
D000588
Amines
D001555
Benzene Derivatives
D006841
Hydrocarbons, Aromatic
D006844
Hydrocarbons, Cyclic
D006838
Hydrocarbons
D013450
Sulfones
D013457
Sulfur Compounds
D014295
Trimethoprim
D004338
Drug Combinations
D004364
Pharmaceutical Preparations
Browse Leaves
Not provided
Browse Branches
Not provided
405 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
0 subjects
FG005336 subjects
FG006333 subjects
FG0070 subjects
FG0080 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG007376 subjects
FG008382 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
BG003
NA
(NA to NA)
Different randomized comparison
BG004NA(NA to NA)Different randomized comparison
BG005NA(NA to NA)Different randomized comparison
BG006NA(NA to NA)Different randomized comparison
BG007NA(NA to NA)Different randomized comparison
BG008NA(NA to NA)Different randomized comparison
BG0096.0(2.4 to 9.3)
NA
Different randomized comparison
BG003NADifferent randomized comparison
BG004NADifferent randomized comparison
BG005NADifferent randomized comparison
BG006NADifferent randomized comparison
BG007NADifferent randomized comparison
BG008NADifferent randomized comparison
BG009NATotal not calculated because data are not available (NA) in one or more arms.
3 years or older
Title
Measurements
BG000409
BG001427
BG002NADifferent randomized comparison
BG003NADifferent randomized comparison
BG004NADifferent randomized comparison
BG005NADifferent randomized comparison
BG006NADifferent randomized comparison
BG007NADifferent randomized comparison
BG008NADifferent randomized comparison
BG009NATotal not calculated because data are not available (NA) in one or more arms.
NA
Different randomized comparison
BG003NADifferent randomized comparison
BG004NADifferent randomized comparison
BG005NADifferent randomized comparison
BG006NADifferent randomized comparison
BG007NADifferent randomized comparison
BG008NADifferent randomized comparison
BG009NATotal not calculated because data are not available (NA) in one or more arms.
Male
BG000298
BG001298
BG002NADifferent randomized comparison
BG003NADifferent randomized comparison
BG004NADifferent randomized comparison
BG005NADifferent randomized comparison
BG006NADifferent randomized comparison
BG007NADifferent randomized comparison
BG008NADifferent randomized comparison
BG009NATotal not calculated because data are not available (NA) in one or more arms.
BG009NATotal not calculated because data are not available (NA) in one or more arms.
NA
Different randomized comparison
BG003NADifferent randomized comparison
BG004NADifferent randomized comparison
BG005NADifferent randomized comparison
BG006NADifferent randomized comparison
BG007283
BG008286
BG009NATotal not calculated because data are not available (NA) in one or more arms.
Zimbabwe
Title
Measurements
BG000NADifferent randomized comparison
BG001NADifferent randomized comparison
BG002NADifferent randomized comparison
BG003NADifferent randomized comparison
BG004NADifferent randomized comparison
BG005NADifferent randomized comparison
BG006NADifferent randomized comparison
BG00793
BG00896
BG009NATotal not calculated because data are not available (NA) in one or more arms.
BG002NA(NA to NA)Different randomized comparison
BG003NA(NA to NA)Different randomized comparison
BG004NA(NA to NA)Different randomized comparison
BG005NA(NA to NA)Different randomized comparison
BG006NA(NA to NA)Different randomized comparison
BG007NA(NA to NA)Different randomized comparison
BG008NA(NA to NA)Different randomized comparison
BG00912.0(7.3 to 17.1)
NA
(NA to NA)
Different randomized comparison
BG00211.7(6.9 to 17.5)
BG00312.0(7.1 to 17.0)
BG00412.5(8.0 to 17.0)
BG005NA(NA to NA)Different randomized comparison
BG006NA(NA to NA)Different randomized comparison
BG007NA(NA to NA)Different randomized comparison
BG008NA(NA to NA)Different randomized comparison
BG00912.0(7.3 to 17.1)
NA
(NA to NA)
Different randomized comparison
BG002NA(NA to NA)Different randomized comparison
BG003NA(NA to NA)Different randomized comparison
BG004NA(NA to NA)Different randomized comparison
BG00533.0(28.0 to 39.0)
BG00633.0(27.0 to 39.0)
BG007NA(NA to NA)Different randomized comparison
BG008NA(NA to NA)Different randomized comparison
BG00933.0(28.0 to 39.0)
NA
(NA to NA)
Different randomized comparison
BG002NA(NA to NA)Different randomized comparison
BG003NA(NA to NA)Different randomized comparison
BG004NA(NA to NA)Different randomized comparison
BG005NA(NA to NA)Different randomized comparison
BG006NA(NA to NA)Different randomized comparison
BG00733.0(26.0 to 39.0)
BG00832.0(26.0 to 39.0)
BG00933.0(26.0 to 39.0)
NA
(NA to NA)
Different randomized comparison
BG002NA(NA to NA)Different randomized comparison
BG003NA(NA to NA)Different randomized comparison
BG004NA(NA to NA)Different randomized comparison
BG0051.8(0.9 to 3.0)
BG0061.8(0.9 to 3.0)
BG007NA(NA to NA)Different randomized comparison
BG008NA(NA to NA)Different randomized comparison
BG0091.8(0.9 to 3.0)
NA
(NA to NA)
Different randomized comparison
BG002NA(NA to NA)Different randomized comparison
BG003NA(NA to NA)Different randomized comparison
BG004NA(NA to NA)Different randomized comparison
BG005NA(NA to NA)Different randomized comparison
BG006NA(NA to NA)Different randomized comparison
BG0072.1(1.6 to 3.2)
BG0082.1(1.8 to 3.2)
BG0092.1(1.6 to 3.2)
(-3.3 to -1.3)
BG002NA(NA to NA)Different randomized comparison
BG003NA(NA to NA)Different randomized comparison
BG004NA(NA to NA)Different randomized comparison
BG005NA(NA to NA)Different randomized comparison
BG006NA(NA to NA)Different randomized comparison
BG007NA(NA to NA)Different randomized comparison
BG008NA(NA to NA)Different randomized comparison
BG009-2.2(-3.3 to -1.3)
NA
(NA to NA)
Different randomized comparison
BG002-2.3(-3.5 to -1.3)
BG003-2.2(-3.2 to -1.4)
BG004-2.2(-3.4 to -1.3)
BG005NA(NA to NA)Different randomized comparison
BG006NA(NA to NA)Different randomized comparison
BG007NA(NA to NA)Different randomized comparison
BG008NA(NA to NA)Different randomized comparison
BG009-2.2(-3.3 to -1.3)
NA
(NA to NA)
Different randomized comparisonDifferent randomized comparison
BG002NA(NA to NA)Different randomized comparison
BG003NA(NA to NA)Different randomized comparison
BG004NA(NA to NA)Different randomized comparison
BG005-1.4(-2.0 to -0.7)
BG006-1.3(-2.0 to -0.6)
BG007NA(NA to NA)Different randomized comparison
BG008NA(NA to NA)Different randomized comparison
BG009-1.4(-2.0 to -0.7)
NA
(NA to NA)
Different randomized comparison
BG002NA(NA to NA)Different randomized comparison
BG003NA(NA to NA)Different randomized comparison
BG004NA(NA to NA)Different randomized comparison
BG005NA(NA to NA)Different randomized comparison
BG006NA(NA to NA)Different randomized comparison
BG007-1.3(-1.9 to -0.6)
BG008-1.3(-1.9 to -0.7)
BG009-1.3(-1.9 to -0.6)
OG000
OG001
Assumptions:
control group (LCM) event rate 3% per year
rates are reduced to 2% per year in the best of the induction-maintenance arms leading to an overall rate of progression to new WHO stage 4 or death of 2.5%
recruitment is over 1.5 years and follow-up for a minimum further 3.5 years.
cumulative loss to follow-up is 10% at 5 years. See below for rest of sample size as this box is not big enough.
Comparison of poisson rates
Statistical analysis plan specified that p-value was to be calculated from the log-rank test, so not provided for the risk difference
0.43
Risk Difference (RD)
0.32
2-Sided
95
-0.47
1.12
Difference is CDM minus LCM
Yes
Non-Inferiority or Equivalence
With assumptions detailed above, >90% power and one-sided alpha=0.05, 1160 children would be required to exclude an increase in progression rate of 1.6% from 2.5% to 4.1% per year in the CDM arm (upper 95% confidence limit of LCM: CDM hazard ratio 1.64).
Units
Counts
Participants
OG000606
OG001600
Title
Denominators
Categories
Title
Measurements
OG000283
OG001282
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.83
Hazard Ratio (HR)
0.98
2-Sided
95
0.83
1.16
Hazard ratio is CDM vs LCM
No
Superiority or Other
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
Units
Counts
Participants
OG000374
OG001388
OG002374
Title
Denominators
Categories
Title
Measurements
OG00016.4± 0.45
OG00117.1± 0.43
OG00217.3± 0.41
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
OG002
Assuming a standard deviation for the change in CD4 percentage from baseline to 72 weeks of 10% (slightly higher than that observed in the PENTA 5 trial) 1200 children would provide at least 80% power to detect a difference in change in CD4% from baseline of more than 2.5% across the 3 groups (F-test with 2-sided alpha=0.05) assuming 20% missing data (loss to follow-up during the first year plus failure to attend the week 72 visit/missing sample).
Regression, Linear
Global test with 2df, adjusted for randomization stratification factors
0.33
No
Superiority or Other
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
Units
Counts
Participants
OG000371
OG001387
OG002378
Title
Denominators
Categories
Title
Measurements
OG00019.8± 0.44
OG00119.6± 0.49
OG00219.2± 0.46
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
OG002
Regression, Linear
Global test with 2df, adjusted for randomization stratification factors
0.69
No
Superiority or Other
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
Units
Counts
Participants
OG000397
OG001404
OG002405
Title
Denominators
Categories
Title
Measurements
OG000157
OG001190
OG002218
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
OG002
Log Rank
Global test with 2df, adjusted for randomization stratification factors
0.0001
No
Superiority or Other
OG000
OG001
Regression, Cox
0.01
Hazard Ratio (HR)
1.32
2-Sided
95
1.07
1.63
HR is Arm B vs A
No
Superiority or Other
OG000
OG002
Regression, Cox
<0.001
Hazard Ratio (HR)
1.58
2-Sided
95
1.29
1.94
No
Superiority or Other
330
OG001331
Title
Denominators
Categories
Title
Measurements
OG000236
OG001242
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Chi-squared
0.65
Risk Difference (RD)
-1.6
2-Sided
95
-8.4
5.2
Difference in suppression <80 copies/ml in once-daily minus twice-daily
Yes
Non-Inferiority or Equivalence
631 children would be required to exclude a 12% lower suppression rate in the once daily group with at least 90% power and two-sided alpha=0.05 (lower 95% confidence limit of difference between once and twice daily -12%, the non-inferiority margin). 630 children retains at least 80% (rather than 90%) power to exclude a 10% (rather than 12%) lower suppression rate in the once daily group with one-sided alpha=0.05 (lower 90% confidence limit of difference between once and twice daily -10%).
336
OG001333
Title
Denominators
Categories
Title
Measurements
OG0001
OG0010
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG00048
OG00172
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Assumptions
5% of children receiving daily cotrimoxazole prophylaxis have a new hospitalisation or death per year
recruitment starts 1 July 2009 with 10% children (those already on ART for >96 weeks) entering immediately, and then the remaining children recruited over the following 15 months as they reach 96 weeks on ART. Follow-up is until March 2012.
cumulative loss to follow-up at March 2012 is 10%. See below for further details as box is not big enough
Log Rank
0.007
Hazard Ratio (HR)
1.64
2-Sided
95
1.14
2.37
Hazard ratio is stop vs continue.
Yes
Non-Inferiority or Equivalence
With assumptions above, at least 80% power and one-sided alpha=0.05, 947 children would be required in the stop/continue cotrimoxazole prophylaxis comparison to exclude an increase in hospitalisation/death rate of 3% from 5% to 8% per year in the stop cotrimoxazole arm (upper 95% confidence limit of stop:continue hazard ratio 1.6).
OG000
OG001
Assumptions
5% of children receiving daily cotrimoxazole prophylaxis have a new hospitalisation or death per year
recruitment starts 1 July 2009 with 10% children (those already on ART for >96 weeks) entering immediately, and then the remaining children recruited over the following 15 months as they reach 96 weeks on ART. Follow-up is until March 2012.
cumulative loss to follow-up at March 2012 is 10%. See below for further details as box is not big enough.
Poisson regression for risk difference
0.006
Risk Difference (RD)
4.0
2-Sided
95
0.8
7.2
Risk difference is stop vs continue.
Yes
Non-Inferiority or Equivalence
With assumptions above, at least 80% power and one-sided alpha=0.05, 947 children would be required in the stop/continue cotrimoxazole prophylaxis comparison to exclude an increase in hospitalisation/death rate of 3% from 5% to 8% per year in the stop cotrimoxazole arm (upper 95% confidence limit of stop:continue hazard ratio 1.6).
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG00055
OG00164
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
0.33
Hazard Ratio (HR)
1.20
2-Sided
95
0.83
1.72
Hazard ratio is stop vs continue.
No
Superiority or Other
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000606
OG001600
OG002397
OG003404
OG004405
Title
Denominators
Categories
Title
Measurements
OG00025
OG00129
OG00220
OG00314
OG00420
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.45
Hazard Ratio (HR)
0.84
2-Sided
95
0.49
1.44
Hazard ratio is CDM vs LCM
No
Superiority or Other
OG002
OG003
OG004
Log Rank
Global test with 2df, adjusted for randomization stratification factors
0.43
No
Superiority or Other
OG002
OG003
Regression, Cox
Adjusted for randomization stratification factors
0.23
Hazard Ratio (HR)
0.66
2-Sided
95
0.33
1.31
Hazard ratio is Arm B vs A
No
Superiority or Other
OG002
OG004
Regression, Cox
Adjusted for randomization stratification factors
0.93
Hazard Ratio (HR)
0.97
2-Sided
95
0.52
1.81
Hazard ratio is Arm C vs A
No
Superiority or Other
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age
Units
Counts
Participants
OG000397
OG001404
OG002405
Title
Denominators
Categories
Title
Measurements
OG00030
OG00128
OG00228
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
OG002
Log Rank
Global test with 2df, adjusted for randomization stratification factors
0.89
No
Superiority or Other
OG000
OG001
Regression, Cox
Adjusted for randomization stratification factors
0.64
Hazard Ratio (HR)
0.89
2-Sided
95
0.53
1.48
Hazard ratio is Arm B vs A
No
Superiority or Other
OG000
OG002
Regression, Cox
Adjusted for randomization stratification factors
0.71
Hazard Ratio (HR)
0.91
2-Sided
95
0.54
1.52
Hazard ratio is Arm C vs A
No
Superiority or Other
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000606
OG001600
OG002397
OG003404
OG004405
Title
Denominators
Categories
Title
Measurements
OG00077
OG00173
OG00273
OG00361
OG00454
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.98
Hazard Ratio (HR)
1.00
2-Sided
95
0.73
1.38
Hazard ratio is CDM vs LCM
No
Superiority or Other
OG002
OG003
OG004
Log Rank
Global test with 2df, adjusted for randomization stratification factors
0.44
No
Superiority or Other
OG002
OG003
Regression, Cox
Adjusted for randomization stratification factors
0.30
Hazard Ratio (HR)
0.82
2-Sided
95
0.55
1.20
Hazard ratio is Arm B vs A
No
Superiority or Other
OG002
OG004
Regression, Cox
Adjusted for randomization stratification factors
0.24
Hazard Ratio (HR)
0.80
2-Sided
95
0.54
1.17
Hazard ratio is Arm C vs A
No
Superiority or Other
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000606
OG001600
OG002397
OG003404
OG004405
Title
Denominators
Categories
Title
Measurements
OG00091
OG00179
OG00264
OG00353
OG00453
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.52
Hazard Ratio (HR)
1.10
2-Sided
95
0.82
1.49
Hazard ratio is CDM vs LCM.
No
Superiority or Other
OG002
OG003
OG004
Log Rank
0.34
Global test with 2df, adjusted for randomization stratification factors
No
Superiority or Other
OG002
OG003
Regression, Cox
Adjusted for randomization stratification factors
0.19
Hazard Ratio (HR)
0.78
2-Sided
95
0.54
1.13
Hazard ratio is Arm B vs A
No
Superiority or Other
OG002
OG004
Regression, Cox
Adjusted for randomization stratification factors
0.25
Hazard Ratio (HR)
0.81
2-Sided
95
0.56
1.16
Hazard ratio is Arm C vs A
No
Superiority or Other
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000606
OG001600
OG002397
OG003404
OG004405
Title
Denominators
Categories
Title
Measurements
OG0000.76± 1.05
OG0010.78± 1.01
OG0020.72± 0.95
OG0030.79± 1.00
OG0040.80± 1.13
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalized estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.71
No
Superiority or Other
OG002
OG003
OG004
Generalized estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.58
No
Superiority or Other
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000606
OG001600
OG002397
OG003404
OG004405
Title
Denominators
Categories
Title
Measurements
OG0000.36± 0.65
OG0010.43± 0.66
OG0020.40± 0.67
OG0030.40± 0.65
OG0040.38± 0.64
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalized estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.07
No
Superiority or Other
OG002
OG003
OG004
Generalized estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.90
No
Superiority or Other
OG001
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000606
OG001600
OG002397
OG003404
OG004405
Title
Denominators
Categories
Title
Measurements
OG0000.65± 1.28
OG0010.61± 1.20
OG0020.56± 1.11
OG0030.64± 1.21
OG0040.69± 1.39
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalized estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.64
No
Superiority or Other
OG002
OG003
OG004
Generalized estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.30
No
Superiority or Other
Units
Counts
Participants
OG000577
OG001563
Title
Denominators
Categories
Title
Measurements
OG00017.2± 0.36
OG00116.7± 0.35
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.45
No
Superiority or Other
Units
Counts
Participants
OG000579
OG001557
Title
Denominators
Categories
Title
Measurements
OG00019.7± 0.38
OG00119.4± 0.38
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.70
No
Superiority or Other
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000326
OG001325
OG002208
OG003231
OG004212
Title
Denominators
Categories
Title
Measurements
OG000408± 22.2
OG001385± 19.8
OG002402± 24.7
OG003447± 28.5
OG004336± 22.5
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.59
0
No
Superiority or Other
OG002
OG003
OG004
Regression, Linear
Global test with 2df, adjusted for randomization stratification factors
0.01
No
Superiority or Other
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000326
OG001320
OG002201
OG003231
OG004214
Title
Denominators
Categories
Title
Measurements
OG000418± 20.8
OG001420± 22.5
OG002446± 25.3
OG003450± 28.9
OG004360± 24.0
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.81
No
Superiority or Other
OG002
OG003
OG004
Regression, Linear
Global test with 2df, adjusted for randomization stratification factors
0.03
No
Superiority or Other
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG00098
OG001102
OG00273
OG00385
OG00442
Title
Denominators
Categories
Title
Measurements
OG00076
OG00178
OG00256
OG00372
OG00426
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Chi-squared
0.86
No
Superiority or Other
OG002
OG003
OG004
Chi-squared
0.02
No
Superiority or Other
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000284
OG001266
OG002168
OG003180
OG004203
Title
Denominators
Categories
Title
Measurements
OG000192
OG001193
OG002127
OG003135
OG004124
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Chi-squared
0.20
No
Superiority or Other
OG002
OG003
OG004
Chi-squared
0.002
No
Superiority or Other
Units
Counts
Participants
OG000606
OG001600
Title
Denominators
Categories
Title
Measurements
OG00028
OG00135
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.22
Hazard Ratio (HR)
0.78
2-Sided
95
0.48
1.29
Hazard ratio is CDM vs LCM
No
Superiority or Other
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000606
OG001600
OG002397
OG003404
OG004405
Title
Denominators
Categories
Title
Measurements
OG00030
OG00142
OG00214
OG00330
OG00428
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
0.09
Hazard Ratio (HR)
0.672
2-Sided
95
0.420
1.075
Hazard ratio is CDM vs LCM
No
Superiority or Other
OG002
OG003
OG004
Log Rank
Global test with 2df, adjusted for randomization stratification factors
0.04
No
Superiority or Other
OG002
OG003
Regression, Cox
Adjusted for randomization stratification factors
0.017
Hazard Ratio (HR)
2.16
2-Sided
95
1.15
4.08
Hazard ratio is Arm B vs A
No
Superiority or Other
OG002
OG004
Regression, Cox
Adjusted for randomization stratification factors
0.034
Hazard Ratio (HR)
2.00
2-Sided
95
1.05
3.80
Hazard ratio is Arm C vs A
No
Superiority or Other
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000606
OG001600
OG002397
OG003404
OG004405
Title
Denominators
Categories
Title
Measurements
OG000147
OG001117
OG00287
OG00382
OG00495
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.04
Hazard Ratio (HR)
1.30
2-Sided
95
1.02
1.66
Hazard ratio is CDM vs LCM
No
Superiority or Other
OG002
OG003
OG004
Log Rank
Global test with 2df, adjusted for randomization stratification factors
0.53
No
Superiority or Other
OG002
OG003
Regression, Cox
Adjusted for randomization stratification factors
0.60
Hazard Ratio (HR)
0.92
2-Sided
95
0.68
1.25
Hazard ratio is Arm B vs A
No
Superiority or Other
OG002
OG004
Regression, Cox
Adjusted for randomization stratification factors
0.56
Hazard Ratio (HR)
1.09
2-Sided
95
0.81
1.46
Hazard ratio is Arm C vs A
No
Superiority or Other
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000606
OG001600
OG002397
OG003404
OG004405
Title
Denominators
Categories
Title
Measurements
OG00031
OG00132
OG0028
OG00330
OG00425
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.84
Hazard Ratio (HR)
0.95
2-Sided
95
0.58
1.56
Hazard ratio is CDM vs LCM
No
Superiority or Other
OG002
OG003
OG004
Log Rank
Global test with 2df, adjusted for randomization stratification factors
0.002
No
Superiority or Other
OG002
OG003
Regression, Cox
Adjusted for randomization stratification factors
0.001
Hazard Ratio (HR)
3.80
2-Sided
95
1.74
8.29
Hazard ratio is Arm B vs A
No
Superiority or Other
OG002
OG004
Regression, Cox
Adjusted for randomization stratification factors
0.006
Hazard Ratio (HR)
3.09
2-Sided
95
1.39
6.85
Hazard ratio is Arm C vs A
No
Superiority or Other
Laboratory Plus Clinical Monitoring (LCM)
Participants were examined by a doctor and had routine full blood count with white cell differential, lymphocyte subsets (CD4, CD8), biochemistry tests (bilirubin, urea, creatinine, aspartate aminotransferase, alanine aminotransferase) at screening, randomisation (lymphocytes only), weeks 4, 8, and 12, then every 12 weeks. All results were returned to physicians for patient management. Other investigations (including tests from the routine panels) could be requested and concomitant drugs prescribed, as clinically indicated at extra patient-initiated or scheduled visits.
OG002
Arm A: ABC+3TC+NNRTI
Other Names:
ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ABC+3TC co-formulated: Kivexa NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children received a standard WHO-recommended regimen of open-label lamivudine, abacavir, plus NNRTI continuously. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG003
Arm B: ZDV+ABC+3TC+NNRTI->ABC+3TC+NNRTI Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus NNRTI subsequently. The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
OG004
Arm C: ZDV+ABC+3TC+NNRTI->ZDV+ABC+3TC Maintenance
Other Names:
ZDV: zidovudine, azidothymidine, Retrovir ABC: abacavir: Ziagen 3TC: lamivudine: Epivir ZDV+3TC co-formulated: Combivir ABC+3TC co-formulated: Kivexa ZDV+ABC+3TC co-formulated: Trizivir NVP: nevirapine, Viramune EFV: efavirenz, Sustiva Children initiated ART using an induction-maintenance approach, starting with open-label four-drug lamivudine, abacavir, NNRTI, plus zidovudine for 36 weeks, then open-label lamivudine, abacavir, plus zidovudine subsequently (triple NRTI maintenance). The NNRTI (nevirapine or efavirenz) was chosen by clinicians according to local availability and age.
Units
Counts
Participants
OG000606
OG001600
OG002397
OG003404
OG004405
Title
Denominators
Categories
Title
Measurements
OG0008.5± 11.1
OG0019.4± 12.4
OG0028.3± 10.8
OG0039.5± 11.8
OG0049.1± 12.7
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalized estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.53
No
Superiority or Other
OG002
OG003
OG004
Generalized estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.46
No
Superiority or Other
331
OG001326
Title
Denominators
Categories
Title
Measurements
OG000230
OG001234
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Chi-squared
0.52
Risk Difference (RD)
-2.3
2-Sided
95
-9.3
4.7
No
Superiority or Other
336
OG001331
Title
Denominators
Categories
Title
Measurements
OG0000.9± 6.1
OG0011.3± 5.4
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.39
Mean Difference (Net)
-0.4
2-Sided
95
-1.2
0.5
Difference is once-daily minus twice-daily
No
Superiority or Other
332
OG001325
Title
Denominators
Categories
Title
Measurements
OG0001.9± 6.3
OG0011.9± 5.3
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.98
Mean Difference (Net)
-0.0
2-Sided
95
-0.9
0.9
Difference is once-daily minus twice-daily
No
Superiority or Other
306
OG001304
Title
Denominators
Categories
Title
Measurements
OG0001.6± 7.0
OG0012.5± 6.3
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.12
Mean Difference (Net)
-0.8
2-Sided
95
-1.9
0.2
Difference is once-daily minus twice-daily
No
Superiority or Other
193
OG001170
Title
Denominators
Categories
Title
Measurements
OG0003± 348
OG001-3± 301
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.82
Mean Difference (Net)
8
2-Sided
95
-60
76
Difference is once-daily minus twice-daily
No
Superiority or Other
190
OG001165
Title
Denominators
Categories
Title
Measurements
OG000-6± 350
OG00127± 316
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.36
Mean Difference (Net)
-33
2-Sided
95
-104
38
Difference is once-daily minus twice-daily
No
Superiority or Other
171
OG001149
Title
Denominators
Categories
Title
Measurements
OG000-26± 445
OG00160± 737
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.20
Mean Difference (Net)
-87
2-Sided
95
-220
46
Difference is once-daily minus twice-daily
No
Superiority or Other
336
OG001333
Title
Denominators
Categories
Title
Measurements
OG0001
OG0014
336
OG001333
Title
Denominators
Categories
Title
Measurements
OG0003
OG0017
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
0.20
Hazard Ratio (HR)
0.43
2-Sided
95
0.11
1.64
Hazard ratio is once-daily vs twice-daily
No
Superiority or Other
336
OG001333
Title
Denominators
Categories
Title
Measurements
OG0009
OG00112
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
0.51
Hazard Ratio (HR)
0.75
2-Sided
95
0.31
1.77
Hazard ratio is once-daily vs twice-daily
No
Superiority or Other
OG000336
OG001333
Title
Denominators
Categories
Title
Measurements
OG0000.28± 0.36
OG0010.32± 0.45
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalized estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.16
No
Superiority or Other
OG000336
OG001333
Title
Denominators
Categories
Title
Measurements
OG0000.01± 0.35
OG001-0.00± 0.37
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalized estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.54
No
Superiority or Other
OG000336
OG001333
Title
Denominators
Categories
Title
Measurements
OG000-0.29± 0.49
OG001-0.35± 0.57
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalised estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.08
No
Superiority or Other
336
OG001333
Title
Denominators
Categories
Title
Measurements
OG00057
OG00154
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.82
Hazard Ratio (HR)
1.04
2-Sided
95
0.72
1.52
Hazard ratio is once-daily vs twice-daily
No
Superiority or Other
336
OG001333
Title
Denominators
Categories
Title
Measurements
OG00030
OG00137
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.31
Hazard Ratio (HR)
0.78
2-Sided
95
0.48
1.27
Hazard ratio is once-daily vs twice-daily
No
Superiority or Other
336
OG001330
Title
Denominators
Categories
Title
Measurements
OG00032
OG00129
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Chi-squared
0.74
No
Superiority or Other
311
OG001309
Title
Denominators
Categories
Title
Measurements
OG00026
OG00125
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Chi-squared
0.90
No
Superiority or Other
336
OG001333
Title
Denominators
Categories
Title
Measurements
OG0008± 12
OG0018± 12
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalized estimating equations
Generalised estimating equation with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.93
No
Superiority or Other
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG00039
OG00177
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
<0.001
Hazard Ratio (HR)
2.21
2-Sided
95
1.50
3.25
Hazard ratio is stop vs continue
No
Superiority or Other
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG0007
OG00110
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.44
Hazard Ratio (HR)
1.47
2-Sided
95
0.56
3.85
Hazard ratio is stop vs continue
No
Superiority or Other
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG0008
OG00119
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.03
Hazard Ratio (HR)
2.40
2-Sided
95
1.05
5.48
Hazard ratio is stop vs continue
No
Superiority or Other
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG0001
OG0014
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.18
Hazard Ratio (HR)
3.98
2-Sided
95
0.44
35.7
Hazard ratio is stop vs continue
No
Superiority or Other
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG0004
OG0017
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.34
Hazard Ratio (HR)
1.80
2-Sided
95
0.53
6.17
Hazard ratio is stop vs continue
No
Superiority or Other
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG0003
OG0012
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.68
Hazard Ratio (HR)
0.69
2-Sided
95
0.12
4.15
Hazard ratio is stop vs continue
No
Superiority or Other
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG000-0.01± 0.37
OG001-0.05± 0.34
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalised estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.07
No
Superiority or Other
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG0000.22± 0.33
OG0010.19± 0.35
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalised estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.19
No
Superiority or Other
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG000-0.24± 0.54
OG001-0.28± 0.45
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalised estimating equations
Generalised estimating equations with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks
0.34
No
Superiority or Other
OG001
360
Title
Denominators
Categories
Title
Measurements
OG0001.7± 5.5
OG0011.1± 5.7
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.13
Mean Difference (Net)
-0.6
2-Sided
95
-1.4
0.2
Difference is stop minus continue
No
Superiority or Other
253
OG001254
Title
Denominators
Categories
Title
Measurements
OG0007± 310
OG001-2± 303
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Regression, Linear
Adjusted for randomization stratification factors
0.68
Mean Difference (Net)
-11
2-Sided
95
-65
42
Difference is stop minus continue
No
Superiority or Other
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG00032
OG00148
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
Adjusted for randomization stratification factors
0.04
Hazard Ratio (HR)
1.60
2-Sided
95
1.02
2.50
Hazard ratio is stop vs continue
No
Superiority or Other
376
OG001382
Title
Denominators
Categories
Title
Measurements
OG0009± 13
OG0018± 13
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Generalised estimating equation
Generalised estimating equation with independent correlation structure and robust standard errors, calculated over all post-randomization visit weeks