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| ID | Type | Description | Link |
|---|---|---|---|
| 10404 | Registry Identifier | DAIDS ES | |
| CHER | Registry Identifier | DAIDS ES | |
| 5R01AI062512-02 | U.S. NIH Grant/Contract | View source | |
| CIPRA-SA Project 2 | Other Identifier | CIPRA |
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The purpose of this study is to compare the effects of anti-HIV drug courses of different lengths in infants who became HIV infected at birth.
In South Africa, an estimated 250,000 infants are born to HIV-infected mothers each year. A high percentage of perinatal HIV infections are due to inadequate or absent mother-to-child transmission prophylaxis. Unfortunately, even with optimal prophylaxis, relatively large numbers of HIV-infected infants will continue to be born and will require antiretroviral therapy (ART). Determining the appropriate times for initiating and interrupting treatment to benefit long-term prognosis in infants is a significant health challenge. Evidence suggests that starting ART early during acute infection will provide long-term benefits. However, longer duration of treatment increases the chance of developing drug-resistant virus, and continuous therapy begun early leads to long-term complications in children. This study will evaluate the efficacy of two different short-course ART strategies in HIV-infected infants from South Africa.
This study will last at least 3.5 years. There are two parts to this study. In Part A, infants with a baseline CD4 percentage (CD4%) of at least 25% and HIV infection diagnosed between 6 and 12 weeks of age will be randomly assigned to one of two treatment strategy arms. Arm 2 infants will receive ART for approximately 40 weeks until their first birthday. Arm 3 infants will receive ART for approximately 96 weeks until their second birthday. Treatment in both arms of Part A will begin with first-line, continuous treatment of zidovudine, lamivudine, and lopinavir/ritonavir. Those who were initially deferred treatment in Arm 1 will be reassessed for initiation of first-line, continuous ART.
First-line ART will be started in Arm 1 or restarted after interruption in Arms 2 and 3 if the appropriate criteria as defined in the protocol is met. First-line treatment of zidovudine, lamivudine, and lopinavir/ritonavir will continue until infants reach a study endpoint; when this occurs, infants will then change to second-line therapy. Second-line ART will consist of didanosine, abacavir sulfate, nevirapine and efavirenz.
All the primary efficacy analysis for this study will focus on the children enrolled in the first phase of Part A (n=377) as proposed by the data safety and monitoring board.
Follow-up visits will take place for 3.5 to 5 years, depending on time of enrollment. All infants will receive routine immunizations and cotrimoxazole (sulfamethoxazole/trimethoprim) prophylaxis from age 6 weeks until Week 40. Study visits will occur at study entry, Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48; and every 12 weeks thereafter. At these visits, infants will have vital sign measurements, a physical exam, and a medical history evaluation. Blood and urine collection will occur at all study visits. Infants' parents or guardians will also be asked to complete an adherence questionnaire.
Participants enrolled in CIPRA-ZA Project 2 are encouraged to enroll in an observational substudy organized by the Wistar Institute (Dr. Luis Montaner, Principal Investigator), in conjunction with the CIPRA team. This study is entitled,"Pediatric Immune Correlates of Early Anti-HIV Therapy." The goal of this 5-year substudy is to evaluate 120 HIV infected children from the parent study twice a year and compare them to HIV uninfected age-matched controls. Children will be evaluated by (a) characterization and identification of the innate and adaptive immune reconstitution outcomes of early (9 or 21 months) therapy in infants infected with HIV at birth and (b) identification of immune correlate outcomes to clinical progression within a period of 2 to 3 years of follow-up after stopping therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Deferred therapy Arm | Experimental | Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line, once daily Nevirapine: Second Line, once daily |
|
| Early therapy for 40 weeks | Experimental | Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line, once daily Nevirapine: Second Line, once daily |
|
| Early therapy for 96 weeks |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Abacavir sulfate | Drug | Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Failure of First Line Therapy or Death | To compare time to failure of first line ART (due to clinical, virological or immunological disease progression, or regimen-limiting ART toxicities) or death among three randomized arms (infants who receive early ART in Arms 2 and 3 and infants in whom ART is deferred until clinical or immunological disease progression in Arm 1) during the study (up to 4.8 years). The number of participants experiencing the events did not reach the 50% survival and thus median time-to-event is not be presented. Therefore we report the number of participants experiencing the events per Arm. | From date of randomization up to failure of first-line therapy or death from any cause, whichever came first, assessed up to 4.8 years |
| Number of Participants Who Experienced Immunological Failure Defined as Failure of CD4% to Reach 20% or CD4% Falls Below 20% on Two Occasions, Within 4 Weeks, at Any Time After the First 24 Weeks of Therapy (Initial Therapy or Restart) | This was part of the primary outcome measure above. The primary outcome was a composite endpoint. The primary outcome analysis only considered the initially enrolled children that were 377 in total (ART-Deferred n=125, Early therapy 40 weeks n=126 and Early therapy 96 weeks n=126). This was part of the primary outcome measure that was a composite endpoint. | This outcome was assessed from the date of randomization to immunological failure. Immunological failure was assessed in the entire study duration of 4.8 years. |
| Number of Participants Who Experienced Regimen-limiting ART Drug Toxicity | Development of toxicity requiring more than one drug substitution within the same class or a switch to a new class of drugs (regimen-limiting toxicity failure) or requiring a permanent treatment discontinuation. This was part of the primary outcome measure that was a composite endpoint. | Regimen limiting drug toxicity was monitored from randomization up to the entire study duration of 4.8 years. |
| Number of Participants Who Experienced Clinical Failure (Defined as Development of Severe CDC Stage B or Stage C Disease.) on Therapy. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Children Experiencing Severe CDC Stage B or Stage C Disease or Death (Cumulative After 3.5 Years) | The outcome measure is defined as a number because it represents the number of children that experienced severe CDC Stage B or Stage C disease or death as defined in the outcome measure title above | Occurrence of severe CDC Stage B or Stage C disease or death (cumulative after 3.5 years), whichever came first, was assessed from randomization up to at least 3.5 years. |
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Inclusion Criteria for Infants:
NOTE: Per Letter of Amendment dated 04/04/07, Part B of this study is no longer recruiting participants. Per Letter of Amendment dated 09/16/08 Arm 1 of this study is longer recruiting.
Exclusion Criteria for Infants:
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| Name | Affiliation | Role |
|---|---|---|
| James McIntyre, MBChB, MRCOG | Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, University of the Witwatersrand | Principal Investigator |
| Avy Violari, MBChB, FCPSA | Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, University of the Witwatersrand | Study Chair |
| Mark F. Cotton, PhD | Department of Pediatrics and Child Health, Faculty of Health Sciences, University of Stellenbosch | Study Chair |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12182375 | Background | Faye A, Bertone C, Teglas JP, Chaix ML, Douard D, Firtion G, Thuret I, Dollfus C, Monpoux F, Floch C, Nicolas J, Vilmer E, Rouzioux C, Mayaux MJ, Blanche S; French Perinatal Study. Early multitherapy including a protease inhibitor for human immunodeficiency virus type 1-infected infants. Pediatr Infect Dis J. 2002 Jun;21(6):518-25. doi: 10.1097/00006454-200206000-00008. | |
| 15578372 | Background | Faye A, Le Chenadec J, Dollfus C, Thuret I, Douard D, Firtion G, Lachassinne E, Levine M, Nicolas J, Monpoux F, Tricoire J, Rouzioux C, Tardieu M, Mayaux MJ, Blanche S; French Perinatal Study Group. Early versus deferred antiretroviral multidrug therapy in infants infected with HIV type 1. Clin Infect Dis. 2004 Dec 1;39(11):1692-8. doi: 10.1086/425739. Epub 2004 Nov 5. |
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Data may be made available through a formal request to the protocol team
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The results are presented for only 377 participants that were enrolled into the three arms (ART-Def 125, ART-40W 126 and ART-96W 126).
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| ID | Title | Description |
|---|---|---|
| FG000 | ART-Deferred | For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. |
| FG001 | Early ART up to 40 Weeks | For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. |
| FG002 | Early ART up to 96 Weeks | For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Deferred Therapy | For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Time to Failure of First Line Therapy or Death | To compare time to failure of first line ART (due to clinical, virological or immunological disease progression, or regimen-limiting ART toxicities) or death among three randomized arms (infants who receive early ART in Arms 2 and 3 and infants in whom ART is deferred until clinical or immunological disease progression in Arm 1) during the study (up to 4.8 years). The number of participants experiencing the events did not reach the 50% survival and thus median time-to-event is not be presented. Therefore we report the number of participants experiencing the events per Arm. | In the analysis of failure of first-line therapy, children enrolled in the ART-Deferred group were used as the reference category in the hazard ratio analysis. | Posted | Count of Participants | Participants | From date of randomization up to failure of first-line therapy or death from any cause, whichever came first, assessed up to 4.8 years |
|
4.8 years, the study duration
Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ART-Deferred | For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 10.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 10.1 | Systematic Assessment |
The CHER study did not include an early continuous therapy Arm, had not been powered to test for differences between early therapy 40 weeks vs. 96 weeks and never assessed in-utero vs. intrapartum infections.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Avy Violari and Prof Mark Cotton | Perinatal HIV Research Unit, Johannesburg and Children's Infectious Diseases Clinical Research Unit, Cape Town all in South Africa | 27 11 989 9702/27 21 938 4219 | 9702/4219 | violari@mweb.co.za |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| C106538 | abacavir |
| D016049 | Didanosine |
| C098320 | efavirenz |
| D019259 | Lamivudine |
| D061466 | Lopinavir |
| C558899 | lopinavir-ritonavir drug combination |
| D019829 | Nevirapine |
| D015215 | Zidovudine |
| ID | Term |
|---|---|
| D007288 | Inosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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This study had two parts: Part A where children were enrolled with CD4% ≥ 25% and Part B where children were enrolled with CD4% < 25%. Part A had three arms: ART-Deferred, ART-40W and ART-96W where ART-40W and ART-96W were the early therapy arms for 40 and 96 weeks respectively. Part B were enrolled into two Arms: ART-40W and ART-96W. The primary efficacy analysis for CHER was based on 377 children that were enrolled in Part A in the first phase of the study. The NIH African data safety and monitoring board recommended that primary analysis be focussed on 377 children enrolled in the first phase of Part A. Additionally, all the key manuscripts have been analysed using this group. Hence all the results presented in clinicaltrials.gov will be specific to this group with three arms.
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| Experimental |
Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line, once daily Nevirapine: Second Line, once daily |
|
|
| Didanosine | Drug | Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Guidelines for switching from first line to second line therapy are available in the protocol. |
|
|
| Efavirenz | Drug | Second Line Regimen: taken orally once daily. Dosage depends on weight. Guidelines for switching from first line to second line therapy are available in the protocol. |
|
|
| Lamivudine | Drug | First Line Regimen: 4 mg/kg taken orally twice daily |
|
|
| Lopinavir/Ritonavir | Drug | First Line Regimen: taken orally twice daily. Dosage depends on age and weight. |
|
|
| Nevirapine | Drug | Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. |
|
|
| Zidovudine | Drug | First Line Regimen: 240 mg/m^2 taken orally twice daily |
|
|
This included development of severe CDC Stage B or Stage C disease.This was part of the primary outcome measure that was a composite endpoint |
| Clinical failure on therapy was assessed at each visit for the entire study duration of 4.8 years. |
| Number of Participants Who Experienced Virological Failure Defined as Confirmed HIV-1 RNA Value of at Least 10,000 Copies Per/ml Recorded on Two Consecutive Separate Occasions After 24 Weeks of Treatment (Initial Therapy or Restart) | This was part of the primary outcome measure that was a composite endpoint that included confirmed HIV-1 RNA value of at least 10,000 copies per/ml recorded on two consecutive separate occasions after 24 weeks of treatment (initial therapy or restart). | Virological failure was assessed from randomization through the entire study duration of 4.8 years. |
| Total Occurrence of Grade 3 or 4 Clinical Events | This was a secondary outcome measure that assessed the total count of Grade 3 or 4 (clinical or laboratory) adverse events. | 4.8 years |
| Total Occurrence of Grade 3 or 4 Laboratory Events | From randomization up to 4.8 years |
| Time From Randomization to Starting or Needing to Start Continuous Therapy | Time from randomization to starting (deferred therapy Arm) or needing to start continuous therapy (early therapy 40 or 96 weeks) | 4.8 years |
| Number of Participants With Indicated Viral Resistance Mutations at the Time of Failure of First Line Therapy | Resistance testing was performed on samples with a VL≥1000 c/ml together with the matched baseline sample, if available. Reverse transcriptase (NRTI and NNRTI) and protease (PI) inhibitor mutations were analysed using a validated in-house population-based sequencing assay and the IAS 2011 mutation list. | 4.8 years |
| Time to Death Alone or Death Plus Life Threatening Stage C Events or HIV Events Associated With Permanent End-organ Damage. | This was a composite endpoint in which the number of children experiencing the events is reported. The number of participants experiencing the events did not reach the 50% survival and thus median time-to-event is not be presented. Therefore, we report the number of participants experiencing the events per Arm. | 4.8 years |
| Hospitalization Rates | Hospitalisation rates in the three arms enrolled in the CHER study | 4.8 years |
| Duration of Hospitalisation | This is the total number of days spent in hospital by the participants and is reported per arm | 4.8 years, the study duration |
| Time to First Hospitalization | To compare time to first hospitalization in the three randomized arms (infants who received early ART in Arms 2 and 3 and those who received deferred ART in Arm 1). Not all participants were hospitalized and thus the upper limits could not be evaluated. | From randomization up to 4.8 years |
| 15275981 | Background | Havens PL, Waters D. Management of the infant born to a mother with HIV infection. Pediatr Clin North Am. 2004 Aug;51(4):909-37, viii. doi: 10.1016/j.pcl.2004.03.004. |
| 15286240 | Background | King SM; American Academy of Pediatrics Committee on Pediatric AIDS; American Academy of Pediatrics Infectious Diseases and Immunization Committee. Evaluation and treatment of the human immunodeficiency virus-1--exposed infant. Pediatrics. 2004 Aug;114(2):497-505. doi: 10.1542/peds.114.2.497. |
| 30418528 | Derived | Mutsaerts EAML, Nunes MC, van Rijswijk MN, Klipstein-Grobusch K, Otwombe K, Cotton MF, Violari A, Madhi SA. Measles Immunity at 4.5 Years of Age Following Vaccination at 9 and 15-18 Months of Age Among Human Immunodeficiency Virus (HIV)-infected, HIV-exposed-uninfected, and HIV-unexposed Children. Clin Infect Dis. 2019 Aug 1;69(4):687-696. doi: 10.1093/cid/ciy964. |
| 26043884 | Derived | Payne H, Mkhize N, Otwombe K, Lewis J, Panchia R, Callard R, Morris L, Babiker A, Violari A, Cotton MF, Klein NJ, Gibb DM. Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis. Lancet Infect Dis. 2015 Jul;15(7):803-9. doi: 10.1016/S1473-3099(15)00087-0. Epub 2015 Jun 1. |
| 24209829 | Derived | Cotton MF, Violari A, Otwombe K, Panchia R, Dobbels E, Rabie H, Josipovic D, Liberty A, Lazarus E, Innes S, van Rensburg AJ, Pelser W, Truter H, Madhi SA, Handelsman E, Jean-Philippe P, McIntyre JA, Gibb DM, Babiker AG; CHER Study Team. Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial. Lancet. 2013 Nov 9;382(9904):1555-63. doi: 10.1016/S0140-6736(13)61409-9. |
| 22029910 | Derived | Hainline C, Taliep R, Sorour G, Nachman S, Rabie H, Dobbels E, van Rensburg AJ, Cornell M, Violari A, Madhi SA, Cotton MF. Early Antiretroviral Therapy reduces the incidence of otorrhea in a randomized study of early and deferred antiretroviral therapy: Evidence from the Children with HIV Early Antiretroviral Therapy (CHER) Study. BMC Res Notes. 2011 Oct 26;4:448. doi: 10.1186/1756-0500-4-448. |
| 19020325 | Derived | Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, Jean-Philippe P, McIntyre JA; CHER Study Team. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med. 2008 Nov 20;359(21):2233-44. doi: 10.1056/NEJMoa0800971. |
| Withdrawal by Subject |
|
| BG001 | Early Therapy up to 40 Weeks | For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. |
| BG002 | Early Therapy up to 96 Weeks | For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. |
| BG003 | Total | Total of all reporting groups |
| Weeks |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | Participants |
|
For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. |
| OG001 | Early Therapy up to 40 Weeks | For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. |
| OG002 | Early Therapy up to 96 Weeks | For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. |
|
|
|
| Primary | Number of Participants Who Experienced Immunological Failure Defined as Failure of CD4% to Reach 20% or CD4% Falls Below 20% on Two Occasions, Within 4 Weeks, at Any Time After the First 24 Weeks of Therapy (Initial Therapy or Restart) | This was part of the primary outcome measure above. The primary outcome was a composite endpoint. The primary outcome analysis only considered the initially enrolled children that were 377 in total (ART-Deferred n=125, Early therapy 40 weeks n=126 and Early therapy 96 weeks n=126). This was part of the primary outcome measure that was a composite endpoint. | Posted | Count of Participants | Participants | This outcome was assessed from the date of randomization to immunological failure. Immunological failure was assessed in the entire study duration of 4.8 years. |
|
|
|
| Primary | Number of Participants Who Experienced Regimen-limiting ART Drug Toxicity | Development of toxicity requiring more than one drug substitution within the same class or a switch to a new class of drugs (regimen-limiting toxicity failure) or requiring a permanent treatment discontinuation. This was part of the primary outcome measure that was a composite endpoint. | Posted | Count of Participants | Participants | Regimen limiting drug toxicity was monitored from randomization up to the entire study duration of 4.8 years. |
|
|
|
| Primary | Number of Participants Who Experienced Clinical Failure (Defined as Development of Severe CDC Stage B or Stage C Disease.) on Therapy. | This included development of severe CDC Stage B or Stage C disease.This was part of the primary outcome measure that was a composite endpoint | Posted | Count of Participants | Participants | Clinical failure on therapy was assessed at each visit for the entire study duration of 4.8 years. |
|
|
|
| Primary | Number of Participants Who Experienced Virological Failure Defined as Confirmed HIV-1 RNA Value of at Least 10,000 Copies Per/ml Recorded on Two Consecutive Separate Occasions After 24 Weeks of Treatment (Initial Therapy or Restart) | This was part of the primary outcome measure that was a composite endpoint that included confirmed HIV-1 RNA value of at least 10,000 copies per/ml recorded on two consecutive separate occasions after 24 weeks of treatment (initial therapy or restart). | Posted | Count of Participants | Participants | Virological failure was assessed from randomization through the entire study duration of 4.8 years. |
|
|
|
| Secondary | Number of Children Experiencing Severe CDC Stage B or Stage C Disease or Death (Cumulative After 3.5 Years) | The outcome measure is defined as a number because it represents the number of children that experienced severe CDC Stage B or Stage C disease or death as defined in the outcome measure title above | Posted | Count of Participants | Participants | Occurrence of severe CDC Stage B or Stage C disease or death (cumulative after 3.5 years), whichever came first, was assessed from randomization up to at least 3.5 years. |
|
|
|
|
| Secondary | Total Occurrence of Grade 3 or 4 Clinical Events | This was a secondary outcome measure that assessed the total count of Grade 3 or 4 (clinical or laboratory) adverse events. | This analysis was only performed on the primary groups including a total of 377 participants | Posted | Number | Count of events | 4.8 years |
|
|
|
|
| Secondary | Total Occurrence of Grade 3 or 4 Laboratory Events | Posted | Number | Count of events | From randomization up to 4.8 years |
|
|
|
|
| Secondary | Time From Randomization to Starting or Needing to Start Continuous Therapy | Time from randomization to starting (deferred therapy Arm) or needing to start continuous therapy (early therapy 40 or 96 weeks) | Posted | Median | Full Range | Weeks | 4.8 years |
|
|
|
| Secondary | Number of Participants With Indicated Viral Resistance Mutations at the Time of Failure of First Line Therapy | Resistance testing was performed on samples with a VL≥1000 c/ml together with the matched baseline sample, if available. Reverse transcriptase (NRTI and NNRTI) and protease (PI) inhibitor mutations were analysed using a validated in-house population-based sequencing assay and the IAS 2011 mutation list. | Mutations presented descriptively were 1) Protease inhibitor mutations and 2) Met184Val mutations were reported. Only 32 participants with viral load above 1,000 copies/ml at their last visit while on treatment were analysed. | Posted | Count of Participants | Participants | 4.8 years |
|
|
|
| Secondary | Time to Death Alone or Death Plus Life Threatening Stage C Events or HIV Events Associated With Permanent End-organ Damage. | This was a composite endpoint in which the number of children experiencing the events is reported. The number of participants experiencing the events did not reach the 50% survival and thus median time-to-event is not be presented. Therefore, we report the number of participants experiencing the events per Arm. | Posted | Count of Participants | Participants | 4.8 years |
|
|
|
|
| Secondary | Hospitalization Rates | Hospitalisation rates in the three arms enrolled in the CHER study | Posted | Number | Events per 100 person years | 4.8 years |
|
|
|
| Secondary | Duration of Hospitalisation | This is the total number of days spent in hospital by the participants and is reported per arm | Posted | Number | Days | 4.8 years, the study duration |
|
|
|
|
| Secondary | Time to First Hospitalization | To compare time to first hospitalization in the three randomized arms (infants who received early ART in Arms 2 and 3 and those who received deferred ART in Arm 1). Not all participants were hospitalized and thus the upper limits could not be evaluated. | Posted | Median | Full Range | Weeks | From randomization up to 4.8 years |
|
|
|
|
| 23 |
| 125 |
| 79 |
| 125 |
| 123 |
| 125 |
| EG001 | Early ART up to 40 Weeks | For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. | 11 | 126 | 60 | 126 | 122 | 126 |
| EG002 | Early ART up to 96 Weeks | For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. | 11 | 126 | 53 | 126 | 125 | 126 |
| Lymphadenitis | Blood and lymphatic system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Lymphadenopathy | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Splenomegaly | Blood and lymphatic system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA 10.1 | Systematic Assessment |
|
| Myocarditis | Cardiac disorders | MedDRA 10.1 | Systematic Assessment |
|
| Cerebral palsy | Congenital, familial and genetic disorders | MedDRA 10.1 | Systematic Assessment |
|
| Hearing loss unilateral | Ear and labyrinth disorders | MedDRA 10.1 | Systematic Assessment |
|
| Gastroenteritis | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| Accidental death | General disorders | MedDRA 10.1 | Systematic Assessment |
|
| Apparent death | General disorders | MedDRA 10.1 | Systematic Assessment |
|
| Death | General disorders | MedDRA 10.1 | Systematic Assessment |
|
| Fever | General disorders | MedDRA 10.1 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 10.1 | Systematic Assessment |
|
| Unknown cause of death | General disorders | MedDRA 10.1 | Systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA 10.1 | Systematic Assessment |
|
| Liver failure | Hepatobiliary disorders | MedDRA 10.1 | Systematic Assessment |
|
| HIV wasting syndrome | Immune system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Abscess | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Bronchiolitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Bronchopneumonia | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Chickenpox | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Croup | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Cytomegalovirus encephalitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Cytomegalovirus hepatitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Dysentery | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Esophageal candidiasis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Laryngotracheo bronchitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Meningitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Miliary tuberculosis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Oesophageal candidiasis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Osteomyelitis chronic | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Parotitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Pharyngitis bacterial | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Pneumococcal pneumonia | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Pneumococcal Sepsis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Pneumocystis carinii pneumonia | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Septicaemia | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| TB | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Tuberculous bronchopneumonia | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Viral meningitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Burns | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
|
| Forearm fracture | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
|
| Fracture | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
|
| Fracture femur | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
|
| Poisoning | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
|
| Skull fracture | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
|
| AST increased | Investigations | MedDRA 10.1 | Systematic Assessment |
|
| Gamma GT increased | Investigations | MedDRA 10.1 | Systematic Assessment |
|
| Hyperkalaemia | Investigations | MedDRA 10.1 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 10.1 | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA 10.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 10.1 | Systematic Assessment |
|
| Failure to thrive | Metabolism and nutrition disorders | MedDRA 10.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 10.1 | Systematic Assessment |
|
| Hypernatremia | Metabolism and nutrition disorders | MedDRA 10.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 10.1 | Systematic Assessment |
|
| Kwashiorkor | Metabolism and nutrition disorders | MedDRA 10.1 | Systematic Assessment |
|
| Lactic acidosis | Metabolism and nutrition disorders | MedDRA 10.1 | Systematic Assessment |
|
| Obesity | Metabolism and nutrition disorders | MedDRA 10.1 | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Febrile seizure | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Focal seizures | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Pneumococcal meningitis | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Seizures | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Acute renal failure | Renal and urinary disorders | MedDRA 10.1 | Systematic Assessment |
|
| Rectovaginal fistula | Reproductive system and breast disorders | MedDRA 10.1 | Systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| Aspiration pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 10.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Splenomegaly | Blood and lymphatic system disorders | MedDRA 10.1 | Systematic Assessment |
|
| Gastroenteritis | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA 10.1 | Systematic Assessment |
|
| AIDS encephalopathy | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Bronchiolitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Bronchopneumonia | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Candida nappy rash | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Candidiasis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Impetigo | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Molluscum Contagiosum | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Mucocutaneous Herpes Simplex | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Oral Candidiasis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Otitis Media | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Persistent Generalised Lymphadenopathy | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Scabies | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| TB | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Tinea | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Tonsilitis | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| Varicella Zoster | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
|
| ALT Increased | Investigations | MedDRA 10.1 | Systematic Assessment |
|
| Gamma GT Increased | Investigations | MedDRA 10.1 | Systematic Assessment |
|
| Failure to thrive | Metabolism and nutrition disorders | MedDRA 10.1 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 10.1 | Systematic Assessment |
|
| Nappy rash | Skin and subcutaneous tissue disorders | MedDRA 10.1 | Systematic Assessment |
|
Not provided
Not provided
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D015224 | Dideoxynucleosides |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D016047 | Zalcitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D011744 | Pyrimidinones |
| D011725 | Pyridines |
| D013936 | Thymidine |
Relative to ART-Def, ART-96W had a 13% difference in the cumulative probability of clinical disease progression or death at 3·5 years
| Proportion test |
| 0.0006 |
| Kaplan-Meier Cummulative Probability |
| 0.20 |
| 2-Sided |
| 95 |
| 0.09 |
| 0.31 |
| Superiority |
| No mutations |
|
The analysis compares ART-96 Weeks relative to ART-Deferred |
| Regression, Cox |
| 0.0009 |
| Hazard Ratio (HR) |
| 0.34 |
| 2-Sided |
| 95 |
| 0.18 |
| 0.64 |
The hazard ratio compares ART-96W relative to the ART-Def arm. |
| Superiority or Other (legacy) |
| Hazard Ratio (HR) |
| 0.583 |
| 2-Sided |
| 95 |
| 0.405 |
| 0.840 |
| Superiority |