ODYSSEY (PENTA 20) | NCT02259127

ID	Type	Description	Link
2014-002632-14	EudraCT Number

ODYSSEY (PENTA 20) | NCT02259127 | Trialant

Sponsor/Collaborators Module

Name	Class
Institut National de la Santé Et de la Recherche Médicale, France	OTHER_GOV
Program for HIV Prevention and Treatment (PHPT)	UNKNOWN
ViiV Healthcare	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
SOC arm	Active Comparator	Standard of Care (SOC) for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors	Drug: Standard of Care
DTG arm	Experimental	DTG + 2 nucleoside transcriptase inhibitors	Drug: Dolutegravir

Name	Type	Description	Arm Group Labels	Other Names
Dolutegravir	Drug		DTG arm	DTG
Standard of Care

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Difference in Proportion With Failure (Clinical or Virological)	Treatment failure by 96 weeks. Estimated using time to the first occurrence of any of the following components: Insufficient virological response defined as < 1 log10 drop at week 24 and switch to second/third line ART for treatment failure Viral Load (VL)>400 c/ml at or after 36 weeks confirmed by next visit Death due to any cause Any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, adjudicated by the Endpoint Review Committee	96 weeks post randomisation

Secondary Outcomes

Measure	Description	Time Frame
HIV-1 RNA <50c/ml at 96 Weeks	Proportion of children with viral load suppression <50 c/ml at 96 weeks.	96 weeks post randomisation
HIV-1 RNA <400c/mL at 96 Weeks	Proportion of children with viral load suppression <400 c/ml at 96 weeks

Other Outcomes

Measure	Description	Time Frame
Mean Change in Weight From Baseline	Mean change in weight from baseline to week 96	96 weeks post randomisation
Mean Change in BMI-for-age Z-score From Baseline	Mean change in BMI-for-age from baseline to week 96. Reporting mean change from the global baseline value across both arms. z-scores (standard scores) are the number of standard deviations the observed data is above or below the population (z-score of 0 represents the population median). Positive z-scores represent the standard deviations above the median and negative z-scores represent the standard deviations below the median. BMI-for-age Z scores indicate: <-3SD severe thinness; <-2SD thinness; -2 to 1SD healthy weight; >1SD overweight; >2SD obese.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

ALL PATIENTS:

Children ≥28 days and <18 years weighing ≥3kg with confirmed HIV-1 infection
Parents/carers and children, where applicable, give informed written consent
Girls aged 12 years or older who have reached menses must have a negative pregnancy test at screening and be willing to adhere to effective methods of contraception if sexually active
Children with co-infections who need to start ART can be enrolled into ODYSSEY according to local/national guidelines
Parents/carers and children, where applicable, willing to adhere to a minimum of 96 weeks' follow-up
- Children weighing 3 to <14kg must be eligible and willing to participate in the Weight band (WB)-Pharmacokinetics (PK)1 substudy unless direct enrolment for the child's weight band has opened following the WB-PK1 substudy and/or dosing information has become available from the IMPAACT P1093 DTG dose-finding study.

ADDITIONAL CRITERIA FOR ODYSSEY A:

• Planning to start first-line ART

ADDITIONAL CRITERIA FOR ODYSSEY B:

Planning to start second-line ART defined as either: (i) switch of at least 2 ART drugs due to treatment failure; or (ii) switch of only the third agent due to treatment failure where drug sensitivity tests show no mutations conferring Nucleoside Reverse Transcriptase Inhibitor (NRTI) resistance
Treated with only one previous ART regimen. Single drug substitutions for toxicity, simplification, changes in national guidelines or drug availability are allowed
At least one NRTI with predicted preserved activity available for a background regimen
In settings where resistance tests are routinely available, at least one new active NRTI from tenofovir disoproxil fumarate, abacavir or zidovudine should have preserved activity based on cumulative results of resistance tests
In settings where resistance tests are not routinely available, children who are due to switch according to national guidelines should have at least one new NRTI predicted to be available from tenofovir disoproxil fumarate, abacavir or zidovudine
Viral load ≥ 500 c/ml at screening visit

Exclusion Criteria:

History or presence of known allergy or contraindications to dolutegravir
History or presence of known allergy or contraindications to proposed available NRTI backbone or proposed available SOC third agent.
Alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal, OR ALT ≥3x upper limit of normal and bilirubin ≥2x upper limit of normal
Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
Anticipated need for Hepatitis C virus (HCV) therapy during the study
Pregnancy or breastfeeding
Evidence of lack of susceptibility to integrase inhibitors or more than a 2-week exposure to antiretrovirals of this class

Contacts/Locations Module

Name	Affiliation	Role
Diana Gibb	Medical Research Council Clinical Trials Unit at UCL	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Universitata Frankfurt		Frankfurt			Germany
UkE Eppendorf Hamburg

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
34965338	Result	Turkova A, White E, Mujuru HA, Kekitiinwa AR, Kityo CM, Violari A, Lugemwa A, Cressey TR, Musoke P, Variava E, Cotton MF, Archary M, Puthanakit T, Behuhuma O, Kobbe R, Welch SB, Bwakura-Dangarembizi M, Amuge P, Kaudha E, Barlow-Mosha L, Makumbi S, Ramsagar N, Ngampiyaskul C, Musoro G, Atwine L, Liberty A, Musiime V, Bbuye D, Ahimbisibwe GM, Chalermpantmetagul S, Ali S, Sarfati T, Wynne B, Shakeshaft C, Colbers A, Klein N, Bernays S, Saidi Y, Coelho A, Grossele T, Compagnucci A, Giaquinto C, Rojo P, Ford D, Gibb DM; ODYSSEY Trial Team. Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. N Engl J Med. 2021 Dec 30;385(27):2531-2543. doi: 10.1056/NEJMoa2108793.
36055295

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
FG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP_ICF	Yes	Yes	Yes	Study Protocol, Statistical Analysis Plan, and Informed Consent Form	Nov 8, 2019

Arm/Group Information

ID	Title	Description
BG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
BG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
BG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
BG003	Standard of Care (<14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Inter-Quartile Range

years

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG00242 ParticipantsBG003

Age, Customized

Count of Participants

Participants

Title	Denominators	Categories
<6 months	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title	Denominators	Categories
Black African	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

Region of Enrollment

Count of Participants

Participants

Title	Denominators	Categories
South Africa	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

ODYSSEY A/B

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

Weight

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

Weight-for-age z-score

z-scores (standard scores) are the number of standard deviations the observed data is above or below the population (z-score of 0 represents the population median). Positive z-scores represent the standard deviations above the median and negative z-scores represent the standard deviations below the median. Weight-for-age Z scores indicate: <-3SD severely underweight; <-2SD moderately underweight; -2 to 2SD healthy weight; >2SD overweight.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357

BMI-for-age z-score

z-scores (standard scores) are the number of standard deviations the observed data is above or below the population (z-score of 0 represents the population median). Positive z-scores represent the standard deviations above the median and negative z-scores represent the standard deviations below the median. BMI-for-age Z scores indicate: <-3SD severe thinness; <-2SD thinness; -2 to 1SD healthy weight; >1SD overweight; >2SD obese.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357

CD4%

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

Viral Load copies/mL

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

History of WHO Staging

WHO clinic staging categorises people living with HIV into four clinical stages from stage 1 (asymptomatic), stage 2 (mild symptoms), stage 3 (advanced symptoms) and stage 4 (AIDS), with stage 4 being the worst outcome.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

CD4

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

Weight

Median

Inter-Quartile Range

kilogram(s)

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

Weight-for-age z-score

Row population differs differs from overall given that weight-for-age Z scores only estimated for participants aged 10 and below.

Median

Inter-Quartile Range

z-score

Title	Denominators	Categories
	ParticipantsBG000116 ParticipantsBG001

BMI-for-age z-score

z-scores (standard scores) are the number of standard deviations the observed data is above or below the population (z-score of 0 represents the population median). Positive z-scores represent the standard deviations above the median and negative z-scores represent the standard deviations below the median. BMI-for-age Z scores indicate: <-3SD severe thinness; <-2SD thinness; -2 to 1SD healthy weight; >1SD overweight; >2SD obese.

Median

Inter-Quartile Range

z-score

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357

CD4%

Data on CD4% at baseline were missing for four participants.

Median

Inter-Quartile Range

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

CD4

Data on CD4 at baseline were missing for four participants.

Median

Inter-Quartile Range

cells/mm^3

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001357 ParticipantsBG002

Log 10 Viral load copies/mL

Data on viral load at baseline were missing for six participants.

Median

Inter-Quartile Range

copies/mL

Title	Denominators	Categories
	ParticipantsBG000350 ParticipantsBG001356 ParticipantsBG002

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

Difference in Proportion With Failure (Clinical or Virological)

Treatment failure by 96 weeks.

Estimated using time to the first occurrence of any of the following components:

Insufficient virological response defined as < 1 log10 drop at week 24 and switch to second/third line ART for treatment failure
Viral Load (VL)>400 c/ml at or after 36 weeks confirmed by next visit
Death due to any cause
Any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, adjudicated by the Endpoint Review Committee

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Count of Participants

Participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003	Standard of Care (<14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG004	Dolutegravir - ODYSSEY A (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART
OG005	Standard of Care - ODYSSEY A (>=14kg Cohort)	Active comparator arm. ODYSSEY A: children starting first-line ART SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor
OG006	Dolutegravir - ODYSSEY B (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY B: children starting second-line ART.
OG007	Standard of Care - ODYSSEY B (>=14kg Cohort)	Active comparator arm. ODYSSEY B: children starting second-line ART. SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors

Units	Counts
Participants	OG000350 OG001357 OG00242 OG003

Title

Denominators

Categories

Insufficient virological response

Title	Measurements
	OG0000 OG0013 OG0020 OG003

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	Statistical Analysis Title: Primary: Diff in adj. KM estimates (>=14kg) Number of subjects included in analysis: 707 Analysis specification: Pre-specified	Bootstrap method		= 0.004		Risk Difference (RD)	-0.08			2-Sided	95	-0.14	-0.03			The probability of having virological or clinical treatment failure by 96 weeks (primary endpoint) was estimated using Kaplan-Meier curves adjusted for stratification factors.		Non-Inferiority	>=14kg cohort: Non-inferiority margin 10% in total population and 12% in ODYSSEY A/ODYSSEY B. <14kg cohort: power for efficacy was not prespecified for this cohort.

Secondary

HIV-1 RNA <50c/ml at 96 Weeks

Proportion of children with viral load suppression <50 c/ml at 96 weeks.

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Count of Participants

Participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003	Standard of Care (<14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors

Secondary

HIV-1 RNA <400c/mL at 96 Weeks

Proportion of children with viral load suppression <400 c/ml at 96 weeks

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Count of Participants

Participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003	Standard of Care (<14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors

Secondary

Mean Change in CD4 Count From Baseline to Week 96

Reporting mean change from the global baseline value across both arms.

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Mean

Standard Error

cells/mm^3

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003	Standard of Care (<14kg Cohort)

Secondary

Mean Change in Total Cholesterol From Baseline to Week 96

Reporting mean change from global baseline value across both arms.

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Mean

Standard Error

mg/dl

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003	Standard of Care (<14kg Cohort)

Secondary

Serious Adverse Events

Incidence of serious adverse events

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Number

participants with events

Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003	Standard of Care (<14kg Cohort)

Secondary

Grade 3 or Above Clinical and Laboratory Adverse Events

Incidence of new clinical and laboratory grade 3 and 4 adverse events

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Number

participants with events

Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003

Secondary

Adverse Events Leading to ART Modification Any Grade

Incidence of adverse events (of any grade) leading to treatment modification

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Number

participants with events

Randomised Phase

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003	Standard of Care (<14kg Cohort)

Secondary

Treatment Failure by 48 Weeks

Treatment failure by 48 weeks. Difference in proportion with clinical or virological failure (as defined above)

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Count of Participants

Participants

48 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003	Standard of Care (<14kg Cohort)

Secondary

Treatment Failure by 144 Weeks

Treatment failure by 144 weeks. Difference in proportion with clinical or virological failure (as defined above)

Note: analysis could not be performed in <14kg cohort due to shorter follow-up

Posted

Count of Participants

Participants

144 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir - ODYSSEY A (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART
OG003	Standard of Care - ODYSSEY A (>=14kg Cohort)

Secondary

WHO 4, Severe WHO 3 Events and Death

Rate of clinical events : WHO 4, severe WHO 3 events and death

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Count of Participants

Participants

Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003

Secondary

Per Protocol: Treatment Failure by 96 Weeks

Per protocol: treatment failure by 96 weeks post randomisation

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Count of Participants

Participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003	Standard of Care (<14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors

Secondary

Any Drug Class Resistance After Virologic Failure

Any drug class resistance after virologic failure 96 weeks post randomisation

Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

Shown are the numbers of participants with resistance after virologic failure, among those with virologic failure by week 96 who had a post-treatment failure resistance test available for the drug class.

Posted

Count of Participants

Participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir - ODYSSEY A (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART
OG001	Standard of Care - ODYSSEY A (>=14kg Cohort)	Active comparator arm. ODYSSEY A: children starting first-line ART SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor
OG002	Dolutegravir - ODYSSEY B (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY B: children starting second-line ART.

Secondary

NRTI Resistance After Virologic Failure

NRTI resistance after virologic failure 96 weeks post randomisation.

Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

Posted

Count of Participants

Participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir - ODYSSEY A (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART
OG001	Standard of Care - ODYSSEY A (>=14kg Cohort)	Active comparator arm. ODYSSEY A: children starting first-line ART SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor
OG002	Dolutegravir - ODYSSEY B (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY B: children starting second-line ART.

Secondary

NNRTI Resistance After Virologic Failure

NNRTI resistance after virologic failure 96 weeks post randomisation.

Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

Posted

Count of Participants

Participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir - ODYSSEY A (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART
OG001	Standard of Care - ODYSSEY A (>=14kg Cohort)	Active comparator arm. ODYSSEY A: children starting first-line ART SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor
OG002	Dolutegravir - ODYSSEY B (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY B: children starting second-line ART.

Secondary

PI Resistance After Virologic Failure

PI resistance after virologic failure 96 weeks post randomisation.

Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

Posted

Count of Participants

Participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir - ODYSSEY A (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART
OG001	Standard of Care - ODYSSEY A (>=14kg Cohort)	Active comparator arm. ODYSSEY A: children starting first-line ART SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor
OG002	Dolutegravir - ODYSSEY B (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY B: children starting second-line ART.

Secondary

INSTI Resistance After Virologic Failure

INSTI resistance after virologic failure 96 weeks post randomisation

Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

Posted

Count of Participants

Participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir - ODYSSEY A (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART
OG001	Dolutegravir - ODYSSEY B (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY B: children starting second-line ART.
OG002	Dolutegravir - ODYSSEY A (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART

Secondary

Emerging Resistance to Any Drug Class After Virologic Failure

Emerging resistance to any drug class after virologic failure 96 weeks post randomisation

Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

>=14kg cohort: among participants with virologic failure and exposure to the drug class, percentage of participants with emerging resistance was estimated under an assumption of the same proportion of new resistance in participants with an available baseline resistance test and those without.

<14kg cohort: percentage reported for participants with whom resistance test was available post-failure and at baseline, and exposed to drug-class during trial.

Dolutegravir - ODYSSEY A (>=14kg cohort): 0 participants had resistance to INSTI post failure Standard of Care - ODYSSEY B (<14kg Cohort) - 0 participants with virological failure and any gene sequenced at baseline and post-failure.

Posted

Number

percentage of participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir - ODYSSEY A (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART
OG001	Standard of Care - ODYSSEY A (>=14kg Cohort)	Active comparator arm. ODYSSEY A: children starting first-line ART SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor

Secondary

NRTI Emerging Resistance After Virologic Failure

NRTI emerging resistance after virologic failure 96 weeks post randomisation

Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

<14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.

Dolutegravir - ODYSSEY A (>=14kg cohort) - 0 participants had resistance post failure.

Dolutegravir - ODYSSEY A (<14kg Cohort) and Standard of Care - ODYSSEY B (<14kg Cohort) - 0 participants with virological failure, exposed to drug-class, and gene sequenced at baseline and post-failure.

Posted

Number

percentage of participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir - ODYSSEY A (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART
OG001	Standard of Care - ODYSSEY A (>=14kg Cohort)	Active comparator arm. ODYSSEY A: children starting first-line ART SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor

Secondary

NNRTI Emerging Resistance After Virologic Failure

NNRTI emerging resistance after virologic failure 96 weeks post randomisation

Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

<14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.

Emergent drug resistance estimated only in participants exposed to drug class during trial (DTG arm not exposed to NNRTI class).

Standard of Care - ODYSSEY A (<14kg Cohort) and Standard of Care - ODYSSEY B (<14kg Cohort) - 0 participants with virological failure, exposed to drug-class, and gene sequenced at baseline and post-failure.

Posted

Number

percentage of participants

96 weeks post randomisation

ID	Title	Description
OG000	Standard of Care - ODYSSEY A (>=14kg Cohort)	Active comparator arm. ODYSSEY A: children starting first-line ART SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor
OG001	Standard of Care - ODYSSEY B (>=14kg Cohort)

Secondary

PI Emerging Resistance After Virologic Failure

PI emerging resistance after virologic failure 96 weeks post randomisation

Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

<14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.

Emergent drug resistance estimated only in participants exposed to drug class during trial (DTG arm not exposed to PI class).

Standard of Care - ODYSSEY A (>=14kg cohort) - 0 participants had resistance post failure.

Standard of Care - ODYSSEY B (<14kg Cohort) - 0 participants with virological failure, exposed to drug-class, and gene sequenced at baseline and post-failure.

Posted

Number

percentage of participants

96 weeks post randomisation

ID	Title	Description
OG000	Standard of Care - ODYSSEY A (>=14kg Cohort)	Active comparator arm. ODYSSEY A: children starting first-line ART SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor
OG001	Standard of Care - ODYSSEY B (>=14kg Cohort)

Secondary

INSTI Emerging Resistance After Virologic Failure

INSTI emerging resistance after virologic failure 96 weeks post randomisation

Major International AIDS Society (IAS) drug-resistance mutations were defined according to the 2019 update of the IAS drug-resistance mutations.

<14kg cohort: percentage reported for participants with whom a resistance test was available post-failure and at baseline, and exposed to drug-class during trial.

The integrase gene was not sequenced for the standard of care arm.

Emergent drug resistance estimated only in participants exposed to drug class during trial (SOC arm not exposed to INSTI drug class).

Dolutegravir - ODYSSEY A (>=14kg cohort) - 0 participants had resistance post failure.

Posted

Number

percentage of participants

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir - ODYSSEY A (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART
OG001	Dolutegravir - ODYSSEY B (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY B: children starting second-line ART.

Secondary

Time to Any New or Recurrent AIDS Defining Event (WHO 4) or Severe WHO 3 Events

Time to any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events adjudicated by the Endpoint Review Committee.

Reported in >=14kg and <14kg papers. >=14kg cohort paper (https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) <14kg cohort paper (https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)

Not Posted

Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

Participants

Secondary

Adherence Questionnaire

The proportion of adherence questionnaires where the participant/carer reports missing a dose within the last week will be compared between randomised groups.

Not Posted

Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

Participants

Secondary

Health-related Quality of Life Questionnaire

Adapted from the Euro Quality of Life Questionnaire (Qol)-5D questionnaire The EQ5D-3L (3-level version of EQ-5D) questionnaire contains five questions about the participants' quality of life: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

Each question has three dimensions: no problems, some problems, and extreme problems.

This analysis reports whether the participant reports any problems (some or extreme). Percentages are of participants completing at least one EQ5D-3L questionnaire during follow-up.

Reported in >=14kg cohort paper (https://www.nejm.org/doi/full/10.1056/NEJMoa2108793)

Not Posted

Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

Participants

Secondary

Acceptability Questionnaire

Number of participants reported to have problems with size, taste or swallowing of the medicines as assessed by Acceptability questionnaire

Not Posted

Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

Participants

Other Pre-specified

Mean Change in Weight From Baseline

Mean change in weight from baseline to week 96

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Mean

Standard Error

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG003	Standard of Care (<14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors

Other Pre-specified

Mean Change in BMI-for-age Z-score From Baseline

Mean change in BMI-for-age from baseline to week 96. Reporting mean change from the global baseline value across both arms.

z-scores (standard scores) are the number of standard deviations the observed data is above or below the population (z-score of 0 represents the population median). Positive z-scores represent the standard deviations above the median and negative z-scores represent the standard deviations below the median. BMI-for-age Z scores indicate: <-3SD severe thinness; <-2SD thinness; -2 to 1SD healthy weight; >1SD overweight; >2SD obese.

Results not presented by ODYSSEY A and B in <14kg cohort due to due ODYSSEY B having too few participants (n=13).

Posted

Mean

Standard Error

Z-score

96 weeks post randomisation

ID	Title	Description
OG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).
OG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
OG002	Dolutegravir (<14kg Cohort)

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (At Risk)
EG000	Dolutegravir (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).	2	350	35	350	350
EG001	Standard of Care (>=14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors	3	357	40	357	357
EG002	Dolutegravir (<14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG).	2	42	11	42	42
EG003	Standard of Care (<14kg Cohort)	Active comparator arm. SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors	4	43	11	43	43
EG004	Dolutegravir - ODYSSEY A (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY A: Children starting first-line ART	2	154	23	154	154
EG005	Standard of Care - ODYSSEY A (>=14kg Cohort)	Active comparator arm. ODYSSEY A: children starting first-line ART SOC for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor	2	157	27	157	157
EG006	Dolutegravir - ODYSSEY B (>=14kg Cohort)	Experimental arm. DTG + 2 nucleoside transcriptase inhibitors. IMP product Dolutegravir (DTG). ODYSSEY B: children starting second-line ART.	0	196	12	196	196
EG007	Standard of Care - ODYSSEY B (>=14kg Cohort)	Active comparator arm. ODYSSEY B: children starting second-line ART. SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors	1	200	13	200	200

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vascular disorders	Vascular disorders	MedDRA (3.0)	Systematic Assessment	EG0001 affected350 at risk EG0010 affected357 at risk EG0020 affected42 at risk EG0030 affected43 at risk EG0041 affected154 at risk EG0050 affected157 at risk EG0060 affected196 at risk EG0070 affected200 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (3.0)	Systematic Assessment	EG0001 affected350 at risk EG0012 affected357 at risk EG0020 affected42 at risk EG003
Immune system disorders	Immune system disorders	MedDRA (3.0)	Systematic Assessment	EG0001 affected350 at risk EG0010 affected357 at risk EG0020 affected42 at risk EG003
Pregnancy, puerperium and perinatal conditions	Pregnancy, puerperium and perinatal conditions	MedDRA (3.0)	Systematic Assessment	EG0000 affected350 at risk EG0011 affected357 at risk EG0020 affected42 at risk EG003
General disorders and administration site conditions	General disorders	MedDRA (3.0)	Systematic Assessment	EG0000 affected350 at risk EG0011 affected357 at risk EG0020 affected42 at risk EG003
Psychiatric disorders	Psychiatric disorders	MedDRA (3.0)	Systematic Assessment	EG0002 affected350 at risk EG0012 affected357 at risk EG0020 affected42 at risk EG003
Injury, poisoning and procedural complications	Injury, poisoning and procedural complications	MedDRA (3.0)	Systematic Assessment	EG0000 affected350 at risk EG0012 affected357 at risk EG0021 affected42 at risk EG003
Investigations	Investigations	MedDRA (3.0)	Systematic Assessment	EG0002 affected350 at risk EG0010 affected357 at risk EG0020 affected42 at risk EG003
Cardiac disorders	Cardiac disorders	MedDRA (3.0)	Systematic Assessment	EG0001 affected350 at risk EG0010 affected357 at risk EG0020 affected42 at risk EG003
Blood and lymphatic system disorders	Blood and lymphatic system disorders	MedDRA (3.0)	Systematic Assessment	EG0003 affected350 at risk EG0013 affected357 at risk EG0021 affected42 at risk EG003
Respiratory, thoracic and mediastinal disorders	Respiratory, thoracic and mediastinal disorders	MedDRA (3.0)	Systematic Assessment	EG0000 affected350 at risk EG0011 affected357 at risk EG0020 affected42 at risk EG003
Nervous system disorders	Nervous system disorders	MedDRA (3.0)	Systematic Assessment	EG0003 affected350 at risk EG0014 affected357 at risk EG0020 affected42 at risk EG003
Gastrointestinal disorders	Gastrointestinal disorders	MedDRA (3.0)	Systematic Assessment	EG0000 affected350 at risk EG0011 affected357 at risk EG0020 affected42 at risk EG003
Hepatobiliary disorders	Hepatobiliary disorders	MedDRA (3.0)	Systematic Assessment	EG0001 affected350 at risk EG0010 affected357 at risk EG0020 affected42 at risk EG003
Renal and urinary disorders	Renal and urinary disorders	MedDRA (3.0)	Systematic Assessment	EG0002 affected350 at risk EG0010 affected357 at risk EG0020 affected42 at risk EG003
Skin and subcutaneous tissue disorders	Skin and subcutaneous tissue disorders	MedDRA (3.0)	Systematic Assessment	EG0002 affected350 at risk EG0011 affected357 at risk EG0020 affected42 at risk EG003
Musculoskeletal and connective tissue disorders	Musculoskeletal and connective tissue disorders	MedDRA (3.0)	Systematic Assessment	EG0002 affected350 at risk EG0011 affected357 at risk EG0020 affected42 at risk EG003
Metabolism and nutrition disorders	Metabolism and nutrition disorders	MedDRA (3.0)	Systematic Assessment	EG0001 affected350 at risk EG0010 affected357 at risk EG0022 affected42 at risk EG003
Infections and infestations	Infections and infestations	MedDRA (3.0)	Systematic Assessment	EG00025 affected350 at risk EG00123 affected357 at risk EG0029 affected42 at risk EG003

Ancestor Terms

ID	Term
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
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases

Title	Measurements
<6kg	BG0000 BG0010 BG00211 BG00312 BG00423
6-<10kg	BG0000 BG0010 BG00220 BG00320 BG004
10-<14kg	BG0000 BG0010 BG00211 BG00311 BG004
14-<20kg	BG00039 BG00143 BG0020 BG0030 BG004
20-<25kg	BG00071 BG00164 BG0020 BG0030 BG004
25-<30kg	BG00058 BG00159 BG0020 BG0030 BG004
30-<35kg	BG00038 BG00151 BG0020 BG0030 BG004
35-<40kg	BG00029 BG00132 BG0020 BG0030 BG004
>=40kg	BG000115 BG001108 BG0020 BG0030 BG004

Title	Measurements
<-3	BG0004 BG0014 BG00214 BG00313 BG00435
-3-<-2	BG00020 BG00112 BG0027 BG0036 BG004
-2-<0	BG00078 BG00183 BG00218 BG00321 BG004
>=0	BG00014 BG00119 BG0023 BG0033 BG004
missing	BG000234 BG001239 BG0020 BG0030 BG004

Title	Measurements
<-3	BG00022 BG00111 BG0023 BG0036 BG00442
-3-<-2	BG00020 BG00128 BG0026 BG0036 BG004
-2-<0	BG000216 BG001219 BG00220 BG00314 BG004
>=0	BG00092 BG00199 BG00213 BG00317 BG004
missing	BG0000 BG0010 BG0020 BG0030 BG004

Title	Measurements
<200 cells/mm^3	BG00088 BG00170 BG0023 BG0034 BG004165
200 to <500 cells/mm^3	BG000118 BG001114 BG0022 BG0033 BG004
>=500 cells/mm^3	BG000144 BG001173 BG00236 BG00333 BG004
Missing	BG0000 BG0010 BG0021 BG0033 BG004

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Statistical Analysis Title: Adjusted Difference (>=14kg) Number of subjects included in analysis: 665 Analysis Specification: Pre-specified	Regression, Logistic	= 0.1377	Risk Difference (RD)	5	2-Sided	95	-1	11	Superiority
OG004 OG005	Statistical Analysis Title: Adjusted difference (ODYSSEY A >=14kg) Number of subjects included in analysis: 286 Analysis Specification: Pre-specified	Regression, Logistic	= 0.8895	Risk Difference (RD)	-1	2-Sided	95	-10	8	Superiority
OG006 OG007	Statistical Analysis Title: Adjusted Difference (ODYSSEY B >=14kg) Number of subjects included in analysis: 381 Analysis Specification: Pre-specified	Regression, Logistic	=0.0435	Risk Difference (RD)	9	2-Sided	95	0.4	17	Superiority
OG002 OG003		Regression, Logistic	0.021	Risk Difference (RD)	26	2-Sided	95	6	47	Superiority

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Statistical Analysis Title: Adjusted Difference (>=14kg) Number of subjects included in analysis: 670 Analysis Specification: Pre-specified	Regression, Logistic	= 0.2256	Risk Difference (RD)	3	2-Sided	95	-2	8	Superiority
OG004 OG005	Statistical Analysis Title: Adjusted Difference (ODYSSEY A >=14kg) Number of subjects included in analysis: 286 Analysis Specification: Pre-specified	Regression, Logistic	= 0.9536	Risk Difference (RD)	0	2-Sided	95	-8	7	Superiority
OG006 OG007	Statistical Analysis Title: Adjusted Difference (ODYSSEY B >=14kg) Number of subjects included in analysis: 384 Analysis Specification: Pre-specified	Regression, Logistic	= 0.1104	Risk Difference (RD)	6	2-Sided	95	-1	12	Superiority
OG002 OG003		Regression, Logistic	0.038	Risk Difference (RD)	19	2-Sided	95	2	37	Superiority

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Statistical Analysis Title: Adjusted Difference (>=14kg) Statistical analysis description: Linear regression of CD4 at week 96, adjusted for randomised arm, baseline CD4 and stratification factors. Presenting mean difference between arms. Number of subjects included in analysis: 707 Analysis Specification: Pre-specified	Regression, Linear	= 0.144	Mean Difference (Final Values)	35	2-Sided	95	-12	82	Superiority
OG004 OG005	Statistical Analysis Title: Adjusted Difference (ODYSSEY A >=14kg) Statistical analysis description: Linear regression of CD4 at week 96, adjusting for randomised arm, baseline CD4 and stratification factors. Presenting mean difference between arms. Number of subjects included in analysis: 311 Analysis Specification: Pre-specified	Regression, Linear	0.185	Mean Difference (Final Values)	44	2-Sided	95	-21	109	Superiority
OG006 OG007	Statistical Analysis Title: Adjusted Difference (ODYSSEY B >=14kg) Statistical analysis description: Linear regression of CD4 at week 96, adjusting for randomised arm, baseline CD4 and stratification factors. Presenting mean difference between arms. Number of subjects included in analysis: 396 Analysis Specification: Pre-specified	Regression, Linear	= 0.427	Mean Difference (Final Values)	27	2-Sided	95	-39	93	Superiority
OG002 OG003		Regression, Linear	0.86	Median Difference (Final Values)	30	2-Sided	95	-308	368	Superiority

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Statistical Analysis Title: Adjusted Difference (>=14kg) Statistical analysis description: Linear regression of total cholesterol at week 96, adjusting for randomised arm, baseline total cholesterol and stratification factors. Presenting mean difference between arms. Number of subjects included in analysis: 707 Analysis Specification: Pre-specified	Regression, Linear	< 0.001	Mean Difference (Final Values)	-15.1	2-Sided	95	-19	-11.1	Superiority
OG002 OG003	Statistical Analysis Title: Adjusted Difference (<14kg) Statistical analysis description: Linear regression of total cholesterol at week 96, adjusting for randomised arm, baseline total cholesterol and stratification factors. Presenting mean difference between arms. Number of subjects included in analysis: 85 Analysis Specification: Pre-specified	Regression, Linear	= 0.0032	Mean Difference (Final Values)	-24.4	2-Sided	95	-40.3	-8.5	Superiority
OG004 OG005	Statistical Analysis Title: Adjusted Difference (ODYSSEY A >=14kg) Statistical analysis description: Linear regression of total cholesterol at week 96, adjusting for randomised arm, baseline total cholesterol and stratification factors. Presenting mean difference between arms. Number of subjects included in analysis: 311 Analysis Specification: Pre-specified	Regression, Linear	< 0.001	Mean Difference (Final Values)	-17.5	2-Sided	95	-23.9	-11.1	Superiority
OG006 OG007	Statistical Analysis Title: Adjusted Difference (ODYSSEY B >=14kg) Statistical analysis description: Linear regression of total cholesterol at week 96, adjusting for randomised arm, baseline total cholesterol and stratification factors. Presenting mean difference between arms. Number of subjects included in analysis: 396 Analysis Specification: Pre-specified	Regression, Linear	< 0.001	Mean Difference (Final Values)	-13.4	2-Sided	95	-18.5	-8.4	Superiority

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Statistical Analysis Title: Adjusted time to first event (>=14kg) Number of subjects included in analysis: 707 Analysis Specification: Pre-specified	Regression, Cox	= 0.53	Hazard Ratio (HR)	0.87	2-Sided	95	0.55	1.36	Superiority
OG002 OG003	Statistical Analysis Title: Adjusted time to first event (<14kg) Number of subjects included in analysis: 85 Analysis Specification: Pre-specified	Regression, Cox	= 0.86	Hazard Ratio (HR)	1.08	2-Sided	95	0.47	2.49	Superiority
OG004 OG005	Statistical Analysis Title: Adjusted time to first event (ODYSSEY A >=14kg) Number of subjects included in analysis: 311 Analysis Specification: Pre-specified	Regression, Cox	= 0.52	Hazard Ratio (HR)	0.83	2-Sided	95	0.48	1.46	Superiority
OG006 OG007	Statistical Analysis Title: Adjusted time to first event (ODYSSEY B >=14kg) Number of subjects included in analysis: 396 Analysis Specification: Pre-specified	Regression, Cox	= 0.86	Hazard Ratio (HR)	0.93	2-Sided	95	0.42	2.04	Superiority

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Statistical Analysis Title: Adjusted time to first event (>=14kg) Number of subjects included in analysis: 707 Analysis Specification: Pre-specified	Regression, Cox	= 0.24	Hazard Ratio (HR)	0.83	2-Sided	95	0.61	1.13	Superiority
OG002 OG003	Statistical Analysis Title: Adjusted time to first event (<14kg) Number of subjects included in analysis: 85 Analysis Specification: Pre-specified	Regression, Cox	= 0.83	Hazard Ratio (HR)	0.93	2-Sided	95	0.5	1.74	Superiority
OG004 OG005	Statistical Analysis Title: Adjusted time to first event (ODYSSEY A >=14kg) Number of subjects included in analysis: 311 Analysis Specification: Pre-specified	Regression, Cox	= 0.57	Hazard Ratio (HR)	1.13	2-Sided	95	0.75	1.7	Superiority
OG006 OG007	Statistical Analysis Title: Adjusted time to first event (ODYSSEY B >=14kg) Number of subjects included in analysis: 396 Analysis Specification: Pre-specified	Regression, Cox	= 0.01	Hazard Ratio (HR)	0.54	2-Sided	95	0.33	0.88	Superiority

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Statistical Analysis Title: Adjusted time to first event (>=14kg) Number of subjects included in analysis: 707 Analysis Specification: Pre-specified	Regression, Cox	= 0.01	Hazard Ratio (HR)	0.29	2-Sided	95	0.11	0.77	Superiority
OG004 OG005	Statistical Analysis Title: Adjusted time to first event (ODYSSEY A >=14kg) Number of subjects included in analysis: 311 Analysis Specification: Pre-specified	Regression, Cox	= 0.13	Hazard Ratio (HR)	0.35	2-Sided	95	0.09	1.33	Superiority
OG006 OG007	Statistical Analysis Title: Adjusted time to first event (ODYSSEY B >=14kg) Number of subjects included in analysis: 396 Analysis Specification: Pre-specified	Regression, Cox	0.055	Hazard Ratio (HR)	0.22	2-Sided	95	0.05	1.03	Superiority

Title

Denominators

ID	Term
D019984	Quality Indicators, Health Care
D011787	Quality of Health Care
D006298	Health Services Administration
D017530	Health Care Quality, Access, and Evaluation