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    Clinical Trial Results:
    A randomised trial of dolutegravir (DTG)-based antiretroviral therapy vs. standard of care (SOC) in children with HIV infection starting first-line or switching to second-line ART

    Summary
    EudraCT number
    		 2014-002632-14
    Trial protocol
    		 ES   DE   PT   FR  
    Global end of trial date
    07 Dec 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Jun 2024
    First version publication date
    20 Jun 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ODYSSEY (PENTA20)
    Additional study identifiers
    ISRCTN number
    		 ISRCTN91737921
    US NCT number
    		 NCT02259127
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Paediatric European Network for Treatment of AIDS (PENTA) Foundation
    Sponsor organisation address
    Corso Stati Uniti 4, Padova, Italy, 35127
    Public contact
    Pablo Rojo, Hospital doce de Octubre / PENTA , 0034 913908569, pablo.rojo@salud.madrid.org
    Scientific contact
    Pablo Rojo, Hospital doce de Octubre / PENTA , 0034 913908569, pablo.rojo@salud.madrid.org
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 Jun 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Jun 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Dec 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the ODYSSEY trial is evaluating the efficacy and safety of once daily DTG-based ART compared with standard of care in children and adolescents starting first- or second-line ART in resource-limited and well-resourced settings.
    Protection of trial subjects
    The details this study were reviewed by an independent committee (a Research Ethics Committee) prior to the trials commencement to ensure that, as far as possible, the safety and wellbeing of participants were protected. A second committee (the Independent Data Monitoring Committee) met regularly during the study to review the interim results as they came out and recommend if the study was safe to continue.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Sep 2016
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 3 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    Portugal: 1
    Country: Number of subjects enrolled
    South Africa: 164
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    Thailand: 61
    Country: Number of subjects enrolled
    Uganda: 374
    Country: Number of subjects enrolled
    United Kingdom: 8
    Country: Number of subjects enrolled
    Zimbabwe: 168
    Worldwide total number of subjects
    792
    EEA total number of subjects
    17
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    76
    Children (2-11 years)
    352
    Adolescents (12-17 years)
    364
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Recruitment to the >=14kg cohort took place between 20th September 2016 and 22nd June 2018 in 8 countries (Germany, Portugal, South Africa, Spain, Thailand, Uganda, United Kingdom, and Zimbabwe) across 29 centres. Recruitment to the <14kg cohort took place between 5th July 2018 and 26th August 2019 in the African countries across 7 centres.

    Pre-assignment
    Screening details
    		 >=14kg cohort, 819 children were assessed for eligibility. 109 were determined ineligible. Additionally, 3 children in >=14kg cohort were randomised in error. <14kg cohort, 102 children were assessed for eligibility. 17 were determined ineligible. See publications for full details.

    Period 1
    Period 1 title
    Overall trial (Overall Period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Dolutegravir (>=14kg cohort)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dolutegravir
    Investigational medicinal product code
    DTG
    Other name
    Pharmaceutical forms
    Capsule, Chewable/dispersible tablet, Tablet
    Routes of administration
    Oral use
    Dosage and administration details

    Arm title
    		 Standard of Care (>=14kg cohort)
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Standard of Care
    Investigational medicinal product code
    SOC
    Other name
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details

    Arm title
    		 Dolutegravir (<14kg Cohort)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dolutegravir
    Investigational medicinal product code
    DTG
    Other name
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details

    Arm title
    		 Standard of Care (<14kg cohort)
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Standard of Care
    Investigational medicinal product code
    SOC
    Other name
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details

    Arm title
    		 Dolutegravir - ODYSSEY A (>=14kg cohort)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dolutegravir
    Investigational medicinal product code
    DTG
    Other name
    Pharmaceutical forms
    Capsule, Chewable/dispersible tablet, Tablet
    Routes of administration
    Oral use
    Dosage and administration details

    Arm title
    		 Standard of Care - ODYSSEY A (>=14kg cohort)
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Standard of Care
    Investigational medicinal product code
    SOC
    Other name
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details

    Arm title
    		 Dolutegravir - ODYSSEY B (>=14kg cohort)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dolutegravir
    Investigational medicinal product code
    DTG
    Other name
    Pharmaceutical forms
    Capsule, Chewable/dispersible tablet, Tablet
    Routes of administration
    Oral use
    Dosage and administration details

    Arm title
    		 Standard of Care - ODYSSEY B (>=14kg cohort)
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Standard of Care
    Investigational medicinal product code
    SOC
    Other name
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details

    Number of subjects in period 1
    		Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir (<14kg Cohort) Standard of Care (<14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Started
    350
    357
    42
    43
    154
    157
    196
    200
    Completed
    350
    357
    42
    43
    154
    157
    196
    200

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Dolutegravir (>=14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Standard of Care (>=14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Dolutegravir (<14kg Cohort)
    Reporting group description
    		 -

    Reporting group title
    Standard of Care (<14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Dolutegravir - ODYSSEY A (>=14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Standard of Care - ODYSSEY A (>=14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Dolutegravir - ODYSSEY B (>=14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Standard of Care - ODYSSEY B (>=14kg cohort)
    Reporting group description
    		 -

    Reporting group values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir (<14kg Cohort) Standard of Care (<14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort) Total
    Number of subjects
    		 350 357 42 43 154 157 196 200 792
    Age categorical
    Units: Subjects
        <6 months
    		 0 0 11 8 0 0 0 0 19
        6 months-<1 year
    		 0 0 5 8 0 0 0 0 13
        1-<2 years
    		 0 0 22 22 0 0 0 0 44
        2-<6 years
    		 15 11 4 5 7 5 8 6 35
        6-<12 years
    		 153 164 0 0 72 84 81 80 317
        12-<18 years
    		 182 182 0 0 75 68 107 114 364
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 12.2 (9.2 to 15.1) 12.1 (8.8 to 14.7) 1.3 (0.5 to 2.0) 1.5 (0.6 to 2.1) 11.9 (9.2 to 14.9) 11.5 (8.5 to 15.0) 12.9 (9.2 to 15.3) 12.5 (9.4 to 14.6) -
    Gender categorical
    Units: Subjects
        Female
    		 174 171 26 18 87 77 87 94 403
        Male
    		 176 186 16 25 67 80 109 106 389
    ODYSSEY A\B
    Units: Subjects
        ODYSSEY A (Starting first-line ART)
    		 154 157 35 37 154 157 0 0 383
        ODYSSEY B (Switching to second-line ART)
    		 196 200 7 6 0 0 196 200 409
    Weight
    Units: Subjects
        <6kg
    		 0 0 11 12 0 0 0 0 23
        6-<10kg
    		 0 0 20 20 0 0 0 0 40
        10-<14kg
    		 0 0 11 11 0 0 0 0 22
        14-<20kg
    		 39 43 0 0 18 20 21 23 82
        20-<25kg
    		 71 64 0 0 33 29 38 35 135
        25-<30kg
    		 58 59 0 0 26 32 32 27 117
        30-<35kg
    		 38 51 0 0 16 17 22 34 89
        35-<40kg
    		 29 32 0 0 12 10 17 22 61
        >=40kg
    		 115 108 0 0 49 49 66 59 223
    Weight-for-age
    Units: Subjects
        <-3
    		 4 4 14 13 2 3 2 1 35
        -3-<-2
    		 20 12 7 6 8 6 12 6 45
        -2-<0
    		 78 83 18 21 39 35 39 48 200
        >=0
    		 14 19 3 3 6 11 8 8 39
        missing
    		 234 239 0 0 99 102 135 137 473
    BMI-for-age
    Units: Subjects
        <-3
    		 22 11 3 6 8 4 14 7 42
        -3-<-2
    		 20 28 6 6 8 16 12 12 60
        -2-<0
    		 216 219 20 14 91 87 125 132 469
        >=0
    		 92 99 13 17 47 50 45 49 221
        missing
    		 0 0 0 0 0 0 0 0 0
    CD4%
    Units: Subjects
        <15%
    		 121 108 7 11 54 56 67 52 247
        15-<30%
    		 152 147 22 18 75 69 77 78 339
        >=30%
    		 77 102 12 11 25 32 52 70 202
        Missing
    		 0 0 1 3 0 0 0 0 4
    Viral Load copies/mL
    Units: Subjects
        <10,000
    		 93 123 4 7 40 48 53 75 227
        10,000-<100,000
    		 159 158 13 5 64 57 95 101 335
        >=100,000
    		 98 75 25 26 50 51 48 24 224
        Missing
    		 0 1 0 5 0 1 0 0 6
    History of WHO Staging
    Units: Subjects
        Stage 1-2
    		 253 265 31 25 116 125 137 140 574
        Stage 3
    		 69 60 6 8 25 22 44 38 143
        Stage 4
    		 28 32 5 10 13 10 15 22 75
    Country
    Units: Subjects
        Uganda
    		 170 161 22 21 46 53 124 108 374
        Zimbabwe
    		 79 67 12 10 39 28 40 39 168
        South Africa
    		 61 83 8 12 36 41 25 42 164
        Thailand
    		 28 33 0 0 24 26 4 7 61
        Europe
    		 12 13 0 0 9 9 3 4 25
    CD4
    Units: Subjects
        <200 cells/mm^3
    		 88 70 3 4 37 38 51 32 165
        200 to <500 cells/mm^3
    		 118 114 2 3 48 56 70 58 237
        >=500 cells/mm^3
    		 144 173 36 33 69 63 75 110 386
        Missing
    		 0 0 1 3 0 0 0 0 4
    Ethnic origin
    Units: Subjects
        Black African
    		 310 313 41 42 123 126 187 187 706
        Asian
    		 28 32 0 0 24 26 4 6 60
        White
    		 5 1 0 0 5 0 0 1 6
        Other
    		 7 11 1 1 2 5 5 6 20
    Age
    Units: Subjects
        <6 months
    		 0 0 11 8 0 0 0 0 19
        6 months-<1 year
    		 0 0 5 8 0 0 0 0 13
        1-<2 years
    		 0 0 22 22 0 0 0 0 44
        2-<6 years
    		 15 11 4 5 7 5 8 6 35
        6-<12 years
    		 153 164 0 0 72 84 81 80 317
        12-<18 years
    		 182 182 0 0 75 68 107 114 364
    Weight
    Units: kilogram(s)
        median (inter-quartile range (Q1-Q3))
    		 30.4 (23.7 to 43.7) 31.0 (23.3 to 42.7) 8.1 (5.6 to 10.0) 8.2 (5.2 to 10.3) 30.0 (23.4 to 45.0) 29.6 (22.8 to 44.8) 30.4 (23.8 to 42.6) 31.9 (23.4 to 41.3) -
    Weight-for-age
    Units: z-score
        median (inter-quartile range (Q1-Q3))
    		 -1.2 (-1.9 to -0.2) -0.9 (-1.6 to -0.2) -2.1 (-3.4 to -1.3) -1.8 (-3.7 to -0.8) -1.2 (-1.6 to -0.3) -0.6 (-1.2 to -0.1) -1.2 (-1.9 to -0.2) -1.1 (-1.6 to -0.5) -
    BMI-for-age
    Units: z-score
        median (inter-quartile range (Q1-Q3))
    		 -0.6 (-1.4 to 0.0) -0.6 (-1.4 to 0.1) -1.1 (-1.9 to 0.2) -0.7 (-2.2 to 0.3) -0.5 (-1.2 to -.2) -0.6 (-1.5 to 0.4) -0.8 (-1.5 to -0.1) -0.6 (-1.3 to 0) -
    CD4%
    Units: percent
        median (inter-quartile range (Q1-Q3))
    		 20 (11 to 29) 22 (13 to 31) 24 (17 to 35) 23 (14 to 30) 19 (12 to 28) 19 (10 to 28) 21 (10 to 32) 25 (15 to 33) -
    CD4
    Units: cells/millimetre
        median (inter-quartile range (Q1-Q3))
    		 444 (196 to 652) 486 (254 to 751) 1639 (1026 to 2327) 1221 (633 to 1870) 453 (210 to 623) 435 (225 to 707) 439 (193 to 716) 554 (285 to 790) -
    Log 10 Viral load copies/mL
    Units: copies\mL
        median (inter-quartile range (Q1-Q3))
    		 4.5 (3.9 to 5.1) 4.4 (3.7 to 4.9) 5.2 (4.4 to 5.8) 5.4 (4.8 to 5.9) 4.6 (4.0 to 5.2) 4.6 (3.8 to 5.1) 4.4 (3.9 to 5.0) 4.2 (3.7 to 4.7) -

    End points

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    End points reporting groups
    Reporting group title
    Dolutegravir (>=14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Standard of Care (>=14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Dolutegravir (<14kg Cohort)
    Reporting group description
    		 -

    Reporting group title
    Standard of Care (<14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Dolutegravir - ODYSSEY A (>=14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Standard of Care - ODYSSEY A (>=14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Dolutegravir - ODYSSEY B (>=14kg cohort)
    Reporting group description
    		 -

    Reporting group title
    Standard of Care - ODYSSEY B (>=14kg cohort)
    Reporting group description
    		 -

    Primary: Treatment failure by 96 weeks

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    End point title
    		 Treatment failure by 96 weeks
    End point description
    End point type
    Primary
    End point timeframe
    96 weeks post randomisation
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir (<14kg Cohort) Standard of Care (<14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    350
    357
    42
    43
    154
    157
    196
    200
    Units: participants
        Insufficient virological response
    0
    3
    0
    0
    0
    2
    0
    1
        Confirmed VL>=400 copies/mL
    40
    64
    9
    16
    10
    26
    30
    38
        Severe WHO 3
    0
    1
    0
    0
    0
    0
    0
    1
        WHO 4
    7
    5
    1
    1
    5
    5
    2
    0
        Death
    0
    2
    2
    4
    0
    1
    0
    1
    Statistical analysis title
    		 Primary: Diff in adj. KM estimates (>=14kg)
    Comparison groups
    Standard of Care (>=14kg cohort) v Dolutegravir (>=14kg cohort)
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.004
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 -0.03
    Statistical analysis title
    		 Diff in adj. KM estimates (Frequentist <14kg)
    Comparison groups
    Standard of Care (<14kg cohort) v Dolutegravir (<14kg Cohort)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.057
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.36
         upper limit
    		 0.02
    Statistical analysis title
    		 Primary:diff in adj. KM estimates (Bayesian <14kg)
    Comparison groups
    Dolutegravir (<14kg Cohort) v Standard of Care (<14kg cohort)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    P-value
    		 = 0.02
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.19
         upper limit
    		 -0.02
    Notes
    [1] - Bayesian estimation was used for the primary analysis of the difference in treatment failure by 96 weeks by arm in <14kg cohort. An informative prior distribution was used based on the treatment effect observed in >=14kg cohort, with relative weight defined by clinical opinion, solicited prior to the main trial results.
    Statistical analysis title
    		 Diff in adj. KM estimates (ODYSSEY A>=14kg)
    Comparison groups
    Standard of Care - ODYSSEY A (>=14kg cohort) v Dolutegravir - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    311
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.003
    Method
    		 bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.21
         upper limit
    		 -0.04
    Statistical analysis title
    		 Diff in adj. KM estimates (ODYSSEY B >=14kg)
    Comparison groups
    Dolutegravir - ODYSSEY B (>=14kg cohort) v Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.22
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.12
         upper limit
    		 0.03

    Secondary: HIV-1 RNA <50c/ml at 96 weeks

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    End point title
    		 HIV-1 RNA <50c/ml at 96 weeks [2]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    335
    330
    146
    140
    189
    192
    Units: participants
        HIV-1 RNA <50c/mL at 96 weeks
    270
    252
    117
    113
    153
    139
    Statistical analysis title
    		 Adjusted Difference (>=14kg)
    Comparison groups
    Dolutegravir (>=14kg cohort) v Standard of Care (>=14kg cohort)
    Number of subjects included in analysis
    665
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1377
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk difference (RD)
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 11
    Statistical analysis title
    		 Adjusted Difference (ODYSSEY A >=14kg)
    Comparison groups
    Dolutegravir - ODYSSEY A (>=14kg cohort) v Standard of Care - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    286
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8895
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 8
    Statistical analysis title
    		 Adjusted Difference (ODYSSEY B >=14kg)
    Comparison groups
    Dolutegravir - ODYSSEY B (>=14kg cohort) v Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    381
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0435
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk difference (RD)
    Point estimate
    9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 17

    Secondary: HIV-1 RNA <400c/ml at 96 weeks

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    End point title
    		 HIV-1 RNA <400c/ml at 96 weeks [3]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    337
    333
    146
    140
    191
    193
    Units: participants
        HIV-1 RNA <400c/mL at 96 weeks
    299
    285
    129
    124
    170
    161
    Statistical analysis title
    		 Adjusted Difference (>=14kg)
    Comparison groups
    Dolutegravir (>=14kg cohort) v Standard of Care (>=14kg cohort)
    Number of subjects included in analysis
    670
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2256
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk difference (RD)
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 8
    Statistical analysis title
    		 Adjusted Difference (ODYSSEY A >=14kg)
    Comparison groups
    Dolutegravir - ODYSSEY A (>=14kg cohort) v Standard of Care - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    286
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9536
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8
         upper limit
    		 7
    Statistical analysis title
    		 Adjusted Difference (ODYSSEY B >=14kg)
    Comparison groups
    Dolutegravir - ODYSSEY B (>=14kg cohort) v Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    384
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1104
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk difference (RD)
    Point estimate
    6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 12

    Secondary: Mean change in CD4 count from baseline to week 96

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    End point title
    		 Mean change in CD4 count from baseline to week 96 [4]
    End point description
    Reporting mean change from the global baseline value (across both arms).
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    350
    357
    154
    157
    196
    200
    Units: cells/mm^3
        arithmetic mean (standard error)
    265 ( 17 )
    230 ( 17 )
    311 ( 23 )
    267 ( 24 )
    228 ( 24 )
    202 ( 24 )
    Statistical analysis title
    		 Adjusted Difference (>=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.
    Comparison groups
    Dolutegravir (>=14kg cohort) v Standard of Care (>=14kg cohort)
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.144
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12
         upper limit
    		 82
    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.
    Comparison groups
    Dolutegravir - ODYSSEY A (>=14kg cohort) v Standard of Care - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    311
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.185
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21
         upper limit
    		 109
    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.
    Comparison groups
    Dolutegravir - ODYSSEY B (>=14kg cohort) v Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.427
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -39
         upper limit
    		 93

    Secondary: Mean change in total cholesterol from baseline to week 96

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    End point title
    		 Mean change in total cholesterol from baseline to week 96
    End point description
    Reporting mean change from the global baseline value (across both arms).
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir (<14kg Cohort) Standard of Care (<14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    350
    357
    42
    43
    154
    157
    196
    200
    Units: mg/dl
        arithmetic mean (standard error)
    -5.0 ( 1.5 )
    9.9 ( 1.5 )
    4.5 ( 5.6 )
    29.6 ( 5.9 )
    2.1 ( 2.3 )
    19.6 ( 2.3 )
    -10.5 ( 1.8 )
    2.8 ( 1.8 )
    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.
    Comparison groups
    Dolutegravir (>=14kg cohort) v Standard of Care (>=14kg cohort)
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -15.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19
         upper limit
    		 -11.1
    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.
    Comparison groups
    Dolutegravir (<14kg Cohort) v Standard of Care (<14kg cohort)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0032
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -24.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -40.3
         upper limit
    		 -8.5
    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.
    Comparison groups
    Dolutegravir - ODYSSEY A (>=14kg cohort) v Standard of Care - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    311
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -17.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.9
         upper limit
    		 -11.1
    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.
    Comparison groups
    Dolutegravir - ODYSSEY B (>=14kg cohort) v Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -13.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.5
         upper limit
    		 -8.4

    Secondary: Serious Adverse Events

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    End point title
    		 Serious Adverse Events
    End point description
    End point type
    Secondary
    End point timeframe
    Randomised phase
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir (<14kg Cohort) Standard of Care (<14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    350
    357
    42
    43
    154
    157
    196
    200
    Units: number of participants with events
    35
    40
    11
    11
    23
    27
    12
    13
    Statistical analysis title
    		 Adjusted time to first event (>=14kg)
    Comparison groups
    Dolutegravir (>=14kg cohort) v Standard of Care (>=14kg cohort)
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.53
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 1.36
    Statistical analysis title
    		 Adjusted time to first event (<14kg)
    Comparison groups
    Standard of Care (<14kg cohort) v Dolutegravir (<14kg Cohort)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.86
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 2.49
    Statistical analysis title
    		 Adjusted time to first event (ODYSSEY A >=14kg)
    Comparison groups
    Dolutegravir - ODYSSEY A (>=14kg cohort) v Standard of Care - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    311
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.52
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 1.46
    Statistical analysis title
    		 Adjusted time to first event (ODYSSEY B >=14kg)
    Comparison groups
    Standard of Care - ODYSSEY B (>=14kg cohort) v Dolutegravir - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.86
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 2.04

    Secondary: Grade 3 or above clinical and laboratory adverse events

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    End point title
    		 Grade 3 or above clinical and laboratory adverse events
    End point description
    End point type
    Secondary
    End point timeframe
    Randomised phase
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir (<14kg Cohort) Standard of Care (<14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    350
    357
    42
    43
    154
    157
    196
    200
    Units: number of participants with events
    73
    86
    19
    21
    48
    43
    25
    43
    Statistical analysis title
    		 Adjusted time to first event (>=14kg)
    Comparison groups
    Dolutegravir (>=14kg cohort) v Standard of Care (>=14kg cohort)
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.24
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 1.13
    Statistical analysis title
    		 Adjusted time to first event (<14kg)
    Comparison groups
    Dolutegravir (<14kg Cohort) v Standard of Care (<14kg cohort)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.83
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 1.74
    Statistical analysis title
    		 Adjusted time to first event (ODYSSEY A >=14kg)
    Comparison groups
    Dolutegravir - ODYSSEY A (>=14kg cohort) v Standard of Care - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    311
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.57
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.7
    Statistical analysis title
    		 Adjusted time to first event (ODYSSEY B >=14kg)
    Comparison groups
    Standard of Care - ODYSSEY B (>=14kg cohort) v Dolutegravir - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.01
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 0.88

    Secondary: Adverse events leading to ART modification any grade

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    End point title
    		 Adverse events leading to ART modification any grade
    End point description
    End point type
    Secondary
    End point timeframe
    Randomised phase
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir (<14kg Cohort) Standard of Care (<14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    350
    357
    42
    43
    154
    157
    196
    200
    Units: number of participants with events
    5
    17
    0
    2
    3
    8
    2
    9
    Statistical analysis title
    		 Adjusted time to first event (>=14kg)
    Comparison groups
    Dolutegravir (>=14kg cohort) v Standard of Care (>=14kg cohort)
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.01
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.11
         upper limit
    		 0.77
    Statistical analysis title
    		 Adjusted time to first event (ODYSSEY A >=14kg)
    Comparison groups
    Dolutegravir - ODYSSEY A (>=14kg cohort) v Standard of Care - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    311
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.13
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.09
         upper limit
    		 1.33
    Statistical analysis title
    		 Adjusted time to first event (ODYSSEY B >=14kg)
    Comparison groups
    Dolutegravir - ODYSSEY B (>=14kg cohort) v Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.055
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.05
         upper limit
    		 1.03

    Secondary: Treatment failure by 48 weeks

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    End point title
    		 Treatment failure by 48 weeks [5]
    End point description
    End point type
    Secondary
    End point timeframe
    48 weeks post randomisation
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    350
    357
    154
    157
    196
    200
    Units: Participants
        Insufficient virologic response
    0
    3
    0
    2
    0
    1
        Confirmed viral load>400c/mL
    13
    31
    4
    12
    9
    19
        Severe WHO stage 3
    0
    1
    0
    0
    0
    1
        WHO stage 4
    7
    5
    5
    5
    2
    0
        Death
    0
    2
    0
    1
    0
    1
    Statistical analysis title
    		 Diff in adj. KM estimates (>=14kg)
    Statistical analysis description
    Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 48 weeks after randomisation.
    Comparison groups
    Dolutegravir (>=14kg cohort) v Standard of Care (>=14kg cohort)
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.003
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 -0.02
    Statistical analysis title
    		 Diff in adj. KM estimates (ODYSSEY A >=14kg)
    Statistical analysis description
    Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 48 weeks after randomisation.
    Comparison groups
    Standard of Care - ODYSSEY A (>=14kg cohort) v Dolutegravir - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    311
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.035
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.13
         upper limit
    		 -0.01
    Statistical analysis title
    		 Diff in adj. KM estimates (ODYSSEY B >=14kg)
    Statistical analysis description
    Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 48 weeks after randomisation.
    Comparison groups
    Dolutegravir - ODYSSEY B (>=14kg cohort) v Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.039
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 -0.004

    Secondary: Treatment failure by 144 weeks

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    End point title
    		 Treatment failure by 144 weeks [6]
    End point description
    End point type
    Secondary
    End point timeframe
    144 week post randomisation
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    350
    357
    154
    157
    196
    200
    Units: Participants
        Insufficient virologic response
    0
    3
    0
    2
    0
    1
        Confirmed viral load>400c/mL
    48
    76
    13
    28
    35
    48
        Severe WHO stage 3
    0
    1
    0
    0
    0
    1
        WHO stage 4
    8
    5
    6
    5
    2
    0
        Death
    0
    2
    0
    1
    0
    1
    Statistical analysis title
    		 Diff in adj. KM estimates (>=14kg)
    Statistical analysis description
    Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 144 weeks after randomisation.
    Comparison groups
    Dolutegravir (>=14kg cohort) v Standard of Care (>=14kg cohort)
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.003
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 -0.04
    Statistical analysis title
    		 Diff in adj. KM estimates (ODYSSEY A >=14kg)
    Statistical analysis description
    Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 144 weeks after randomisation.
    Comparison groups
    Dolutegravir - ODYSSEY A (>=14kg cohort) v Standard of Care - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    311
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.009
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.21
         upper limit
    		 -0.03
    Statistical analysis title
    		 Diff in adj. KM estimates (ODYSSEY B >=14kg)
    Statistical analysis description
    Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 144 weeks after randomisation.
    Comparison groups
    Dolutegravir - ODYSSEY B (>=14kg cohort) v Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.079
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.01

    Secondary: WHO 4, severe WHO 3 and death

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    End point title
    		 WHO 4, severe WHO 3 and death
    End point description
    End point type
    Secondary
    End point timeframe
    Randomised phase
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir (<14kg Cohort) Standard of Care (<14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    350
    357
    42
    43
    154
    157
    196
    200
    Units: number of participants with events
    8
    8
    3
    6
    6
    6
    2
    2
    Statistical analysis title
    		 Adjusted time to first event (>=14kg)
    Comparison groups
    Dolutegravir (>=14kg cohort) v Standard of Care (>=14kg cohort)
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.993
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.38
         upper limit
    		 2.68
    Statistical analysis title
    		 Adjusted time to first event (<14kg)
    Comparison groups
    Dolutegravir (<14kg Cohort) v Standard of Care (<14kg cohort)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.33
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.13
         upper limit
    		 2
    Statistical analysis title
    		 Adjusted time to first event (ODYSSEY A >=14kg)
    Comparison groups
    Dolutegravir - ODYSSEY A (>=14kg cohort) v Standard of Care - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    311
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.991
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 3.12
    Statistical analysis title
    		 Adjusted time to first event (ODYSSEY B >=14kg)
    Comparison groups
    Standard of Care - ODYSSEY B (>=14kg cohort) v Dolutegravir - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.997
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.14
         upper limit
    		 7.13

    Secondary: Per protocol: treatment failure by 96 weeks

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    End point title
    		 Per protocol: treatment failure by 96 weeks
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir (<14kg Cohort) Standard of Care (<14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    340
    337
    42
    43
    150
    145
    190
    192
    Units: Participants
    44
    62
    12
    20
    13
    28
    31
    34
    Statistical analysis title
    		 Diff in adj. KM estimates (>=14kg)
    Statistical analysis description
    Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 96 weeks after randomisation.
    Comparison groups
    Dolutegravir (>=14kg cohort) v Standard of Care (>=14kg cohort)
    Number of subjects included in analysis
    677
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.015
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.12
         upper limit
    		 -0.01
    Statistical analysis title
    		 Adjusted Difference (frequentist <14kg)
    Statistical analysis description
    Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 96 weeks after randomisation.
    Comparison groups
    Dolutegravir (<14kg Cohort) v Standard of Care (<14kg cohort)
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.075
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.172
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.362
         upper limit
    		 0.029
    Statistical analysis title
    		 Adjusted Difference (ODYSSEY A >=14kg)
    Statistical analysis description
    Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 96 weeks after randomisation.
    Comparison groups
    Dolutegravir - ODYSSEY A (>=14kg cohort) v Standard of Care - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    295
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.004
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.126
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.21
         upper limit
    		 -0.036
    Statistical analysis title
    		 Adjusted Difference (ODYSSEY B >=14kg)
    Statistical analysis description
    Difference in adjusted (for stratification factors) Kaplan-Meier survival function estimates at 96 weeks after randomisation.
    Comparison groups
    Dolutegravir - ODYSSEY B (>=14kg cohort) v Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    382
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.547
    Method
    		 Bootstrap method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.023
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.096
         upper limit
    		 0.056

    Secondary: Any drug class resistance after virologic failure

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    End point title
    		 Any drug class resistance after virologic failure [7]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    11
    29
    29
    40
    Units: Participants
    0
    28
    23
    36
    No statistical analyses for this end point

    Secondary: NRTI resistance after virologic failure

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    End point title
    		 NRTI resistance after virologic failure [8]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    11
    29
    29
    40
    Units: Participants
    0
    18
    21
    31
    No statistical analyses for this end point

    Secondary: NNRTI resistance after virologic failure

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    End point title
    		 NNRTI resistance after virologic failure [9]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    11
    29
    29
    40
    Units: Participants
    0
    27
    22
    36
    No statistical analyses for this end point

    Secondary: PI resistance after virologic failure

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    End point title
    		 PI resistance after virologic failure [10]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    11
    29
    29
    40
    Units: Participants
    0
    0
    2
    3
    No statistical analyses for this end point

    Secondary: INSTI resistance after virologic failure

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    End point title
    		 INSTI resistance after virologic failure [11]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    11
    22
    Units: Participants
    0
    4
    No statistical analyses for this end point

    Secondary: Any drug class emerging resistance after virologic failure

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    End point title
    		 Any drug class emerging resistance after virologic failure [12]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    0 [13]
    21
    6
    6
    Units: Percent
        number (not applicable)
    97
    22
    19
    Notes
    [13] - 0 participants had resistance to INSTI post failure
    No statistical analyses for this end point

    Secondary: NRTI emerging resistance after virologic failure

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    End point title
    		 NRTI emerging resistance after virologic failure [14]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    0 [15]
    13
    2
    3
    Units: percent
        number (not applicable)
    62
    8
    10
    Notes
    [15] - 0 participants had resistance post failure
    No statistical analyses for this end point

    Secondary: NNRTI emerging resistance after virologic failure

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    End point title
    		 NNRTI emerging resistance after virologic failure [16]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Standard of Care - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    19
    2
    Units: percent
        number (not applicable)
    88
    100
    No statistical analyses for this end point

    Secondary: PI emerging resistance after virologic failure

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    End point title
    		 PI emerging resistance after virologic failure [17]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    2
    Units: Perc
        number (not applicable)
    5
    No statistical analyses for this end point

    Secondary: INSTI emerging resistance after virologic failure

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    End point title
    		 INSTI emerging resistance after virologic failure [18]
    End point description
    End point type
    Secondary
    End point timeframe
    96 weeks post randomisation
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    0 [19]
    4
    Units: percent
        number (not applicable)
    18
    Notes
    [19] - 0 participants had resistance post failure
    No statistical analyses for this end point

    Other pre-specified: Mean change in weight from baseline to week 96

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    End point title
    		 Mean change in weight from baseline to week 96 [20]
    End point description
    Reporting mean change from the global baseline value (across both arms).
    End point type
    Other pre-specified
    End point timeframe
    96 weeks post randomisation
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    350
    357
    154
    157
    196
    200
    Units: kg
        arithmetic mean (standard error)
    7.1 ( 0.3 )
    6.1 ( 0.3 )
    7.8 ( 0.4 )
    6.5 ( 0.4 )
    6.7 ( 0.3 )
    5.9 ( 0.3 )
    Statistical analysis title
    		 Adjusted Difference (>=14kg)
    Comparison groups
    Standard of Care (>=14kg cohort) v Dolutegravir (>=14kg cohort)
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3
         upper limit
    		 1.7
    Statistical analysis title
    		 Adjusted Difference (ODYSSEY A >=14kg)
    Statistical analysis description
    Linear regression of weight at week 96, adjusting for randomised arm, baseline weight and stratification factors. Presenting mean difference between arms.
    Comparison groups
    Standard of Care - ODYSSEY A (>=14kg cohort) v Dolutegravir - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    311
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.024
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.2
         upper limit
    		 2.5
    Statistical analysis title
    		 Adjusted Difference (ODYSSEY B >=14kg)
    Statistical analysis description
    Linear regression of weight at week 96, adjusting for randomised arm, baseline weight and stratification factors. Presenting mean difference between arms.
    Comparison groups
    Dolutegravir - ODYSSEY B (>=14kg cohort) v Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.075
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 1.6

    Other pre-specified: Mean change in BMI-for-age from baseline to week 96

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    End point title
    		 Mean change in BMI-for-age from baseline to week 96 [21]
    End point description
    Reporting mean change from the global baseline value (across both arms).
    End point type
    Other pre-specified
    End point timeframe
    96 weeks post randomisation
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Please see publication on <14kg results.
    End point values
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir - ODYSSEY A (>=14kg cohort) Standard of Care - ODYSSEY A (>=14kg cohort) Dolutegravir - ODYSSEY B (>=14kg cohort) Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects analysed
    350
    357
    154
    157
    196
    200
    Units: Z-score
        arithmetic mean (standard error)
    0.24 ( 0.04 )
    0.11 ( 0.04 )
    0.36 ( 0.07 )
    0.20 ( 0.07 )
    0.14 ( 0.05 )
    0.04 ( 0.05 )
    Statistical analysis title
    		 Adjusted Difference (>=14kg)
    Statistical analysis description
    Linear regression of BMI-for-age at week 96, adjusting for randomised arm, baseline BMI-for-age and stratification factors. Presenting mean difference between arms.
    Comparison groups
    Standard of Care (>=14kg cohort) v Dolutegravir (>=14kg cohort)
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.036
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.01
         upper limit
    		 0.25
    Statistical analysis title
    		 Adjusted Difference (ODYSSEY A >=14kg)
    Statistical analysis description
    Linear regression of BMI-for-age at week 96, adjusting for randomised arm, baseline BMI-for-age and stratification factors. Presenting mean difference between arms.
    Comparison groups
    Dolutegravir - ODYSSEY A (>=14kg cohort) v Standard of Care - ODYSSEY A (>=14kg cohort)
    Number of subjects included in analysis
    311
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.092
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 0.36
    Statistical analysis title
    		 Adjusted Difference (ODYSSEY B >=14kg)
    Statistical analysis description
    Linear regression of BMI-for-age at week 96, adjusting for randomised arm, baseline BMI-for-age and stratification factors. Presenting mean difference between arms.
    Comparison groups
    Dolutegravir - ODYSSEY B (>=14kg cohort) v Standard of Care - ODYSSEY B (>=14kg cohort)
    Number of subjects included in analysis
    396
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.176
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.05
         upper limit
    		 0.25

    Adverse events

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    Adverse events information [1]
    Timeframe for reporting adverse events
    Randomised phase
    Adverse event reporting additional description
    Non-serious AEs:There was no single diagnosis reported for 5% or more of participants. Details of all AEs are reported in the supplementary materials of the >=14kg cohort paper (https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) and the <14kg cohort paper (https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    3.0
    Reporting groups
    Reporting group title
    Dolutegravir (>=14kg cohort)
    Reporting group description
    		 Non-serious AEs:There was no single diagnosis reported for 5% or more of participants. Details of all AEs are reported in the supplementary materials of the >=14kg cohort paper https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) and the <14kg cohort paper (https://www. thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)

    Reporting group title
    Standard of Care (>=14kg cohort)
    Reporting group description
    		 Non-serious AEs:There was no single diagnosis reported for 5% or more of participants. Details of all AEs are reported in the supplementary materials of the >=14kg cohort paper https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) and the <14kg cohort paper (https://www. thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)

    Reporting group title
    Dolutegravir (<14kg Cohort)
    Reporting group description
    		 Non-serious AEs:There was no single diagnosis reported for 5% or more of participants. Details of all AEs are reported in the supplementary materials of the >=14kg cohort paper https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) and the <14kg cohort paper (https://www. thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)

    Reporting group title
    Standard of Care (<14kg cohort)
    Reporting group description
    		 Non-serious AEs:There was no single diagnosis reported for 5% or more of participants. Details of all AEs are reported in the supplementary materials of the >=14kg cohort paper https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) and the <14kg cohort paper (https://www. thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: Non-serious AEs:There was no single diagnosis reported for 5% or more of participants. Details of all AEs are reported in the supplementary materials of the >=14kg cohort paper https://www.nejm.org/doi/full/10.1056/NEJMoa2108793) and the <14kg cohort paper (https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00163-1/fulltext)
    Serious adverse events
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir (<14kg Cohort) Standard of Care (<14kg cohort)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    35 / 350 (10.00%)
    40 / 357 (11.20%)
    11 / 42 (26.19%)
    11 / 43 (25.58%)
         number of deaths (all causes)
    2
    3
    2
    4
         number of deaths resulting from adverse events
    2
    3
    2
    4
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps): serious adverse events
         subjects affected / exposed
    1 / 350 (0.29%)
    2 / 357 (0.56%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Vascular disorders
    Vascular disorders: serious adverse events
         subjects affected / exposed
    1 / 350 (0.29%)
    0 / 357 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy, puerperium and perinatal conditions: serious adverse events
         subjects affected / exposed
    0 / 350 (0.00%)
    1 / 357 (0.28%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General disorders and administration site conditions: serious adverse events
         subjects affected / exposed
    0 / 350 (0.00%)
    1 / 357 (0.28%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Immune system disorders: serious adverse events
         subjects affected / exposed
    1 / 350 (0.29%)
    0 / 357 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory, thoracic and mediastinal disorders: serious adverse events
         subjects affected / exposed
    0 / 350 (0.00%)
    1 / 357 (0.28%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychiatric disorders: serious adverse events
         subjects affected / exposed
    2 / 350 (0.57%)
    2 / 357 (0.56%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Investigations: serious adverse events
         subjects affected / exposed
    2 / 350 (0.57%)
    0 / 357 (0.00%)
    0 / 42 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Injury, poisoning and procedural complications: serious adverse events
         subjects affected / exposed
    0 / 350 (0.00%)
    2 / 357 (0.56%)
    1 / 42 (2.38%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cardiac disorders
    Cardiac disorders: serious adverse events
         subjects affected / exposed
    1 / 350 (0.29%)
    0 / 357 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Nervous system disorders: serious adverse events
         subjects affected / exposed
    3 / 350 (0.86%)
    4 / 357 (1.12%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders: serious adverse events
         subjects affected / exposed
    3 / 350 (0.86%)
    3 / 357 (0.84%)
    1 / 42 (2.38%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 4
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal disorders: serious adverse events
         subjects affected / exposed
    0 / 350 (0.00%)
    1 / 357 (0.28%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatobiliary disorders: serious adverse events
         subjects affected / exposed
    1 / 350 (0.29%)
    0 / 357 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders: serious adverse events
         subjects affected / exposed
    2 / 350 (0.57%)
    1 / 357 (0.28%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal and urinary disorders: serious adverse events
         subjects affected / exposed
    2 / 350 (0.57%)
    0 / 357 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal and connective tissue disorders: serious adverse events
         subjects affected / exposed
    2 / 350 (0.57%)
    2 / 357 (0.56%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Infections and infestations: serious adverse events
         subjects affected / exposed
    25 / 350 (7.14%)
    23 / 357 (6.44%)
    9 / 42 (21.43%)
    9 / 43 (20.93%)
         occurrences causally related to treatment / all
    0 / 30
    0 / 24
    0 / 11
    0 / 16
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 3
    Metabolism and nutrition disorders
    Metabolism and nutrition disorders: serious adverse events
         subjects affected / exposed
    1 / 350 (0.29%)
    0 / 357 (0.00%)
    2 / 42 (4.76%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Dolutegravir (>=14kg cohort) Standard of Care (>=14kg cohort) Dolutegravir (<14kg Cohort) Standard of Care (<14kg cohort)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 350 (0.00%)
    0 / 357 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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