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    Clinical Trial Results:
    A Phase III, randomized, multicenter, parallel-group, noninferiority study evaluating the efficacy, safety, and tolerability of switching to dolutegravir plus rilpivirine from current INI-, NNRTI-, or PI-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed

    Summary
    EudraCT number
    		 2014-005147-40
    Trial protocol
    		 ES   DE   NL   BE   GB   IT  
    Global end of trial date

    Results information
    Results version number
    		 v5
    This version publication date
    10 Oct 2020
    First version publication date
    13 Aug 2017
    Other versions
    		 v1 , v2 , v3 , v4 , v6
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    201636
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    ViiV Healthcare
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343,
    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
    Interim
    Date of interim/final analysis
    20 Feb 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Sep 2016
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the non-inferior antiviral activity of switching to dolutegravir (DTG) plus rilpivirine (RPV) once daily compared to continuation of current antiretroviral regimen (CAR) over 48 weeks in HIV-1 infected antiretroviral therapy (ART)-experienced virologically suppressed subjects
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Apr 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Scientific research
    Long term follow-up duration
    		 4 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 5
    Country: Number of subjects enrolled
    Australia: 10
    Country: Number of subjects enrolled
    Belgium: 18
    Country: Number of subjects enrolled
    Canada: 29
    Country: Number of subjects enrolled
    France: 33
    Country: Number of subjects enrolled
    Germany: 17
    Country: Number of subjects enrolled
    Italy: 20
    Country: Number of subjects enrolled
    Netherlands: 9
    Country: Number of subjects enrolled
    Russian Federation: 35
    Country: Number of subjects enrolled
    Spain: 191
    Country: Number of subjects enrolled
    Taiwan: 54
    Country: Number of subjects enrolled
    United States: 86
    Country: Number of subjects enrolled
    United Kingdom: 3
    Worldwide total number of subjects
    510
    EEA total number of subjects
    291
    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)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    490
    From 65 to 84 years
    20
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was a 148-week, Phase III, randomized, open-label, active-controlled, multicenter, parallel-group, non-inferiority study to assess the antiviral activity and safety of a two-drug regimen of dolutegravir (DTG) + rilpivirine (RPV) compared with current antiretroviral regimen (CAR). The study was conducted at 65 centers in 13 countries.

    Pre-assignment
    Screening details
    		 Total 641 participants were screened (131 failed), 510 participants were randomized and 2 participants withdrew before being exposed to study drug. The study included a Screening phase, an early switch phase, a late switch phase, and a continuation phase.The results presented are based on the interim analysis of the Late Switch Phase (Week 148).

    Period 1
    Period 1 title
    Early Switch Phase (Up to Week 52)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 DTG + RPV
    Arm description
    		 Participants received DTG 50 milligrams (mg) + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase. Participants continued to receive DTG 50 mg + RPV 25 mg up to Week 148 during the Late Switch Phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dolutegravir Tablets 50 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received dolutegravir tablets 50 mg once daily, with a meal, in an open-label fashion up to Week 52 during early switch phase.

    Investigational medicinal product name
    Rilpivirine Tablets 25 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received rilpivirine tablets 25 mg once daily, with a meal, in an open-label fashion up to Week 52 during early switch phase.

    Arm title
    		 Current antiretroviral regimen
    Arm description
    		 Participants continued to receive their current antiretroviral regimen (two nucleoside reverse transcriptase inhibitors [NRTIs] + a third agent). A third agent included either an: integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). CAR was administered according to the approved labeling in an open-label fashion up to Week 52 during early switch phase. At Week 52, participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) <50 copies per milliliter (c/mL), switched to DTG 50 mg + RPV 25 mg once daily and were followed until Week 148.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Current antiretroviral regimen (not IMP)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received their current antiretroviral regimen (2 NRTIs + a third agent). A third agent included either of INI, NNRTI, or PI. CAR was administered according to the approved labeling in an open-label fashion up to Week 52 during early switch phase.

    Number of subjects in period 1 [1]
    		DTG + RPV Current antiretroviral regimen
    Started
    252
    256
    Completed
    239
    238
    Not completed
    13
    18
         Consent withdrawn by subject
    3
    7
         Physician decision
    -
    2
         Adverse event, non-fatal
    6
    2
         Lost to follow-up
    1
    2
         Lack of efficacy
    2
    1
         Protocol deviation
    1
    4
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Total number of participants enrolled were 510. Of which, 2 participants withdrew before being exposed to study drug.
    Period 2
    Period 2 title
    Late Switch Phase (Week 52 to Week 148)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 DTG + RPV
    Arm description
    		 Participants received DTG 50 milligrams (mg) + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase. Participants continued to receive DTG 50 mg + RPV 25 mg up to Week 148 during the Late Switch Phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rilpivirine Tablets 25 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received rilpivirine tablets 25 mg once daily, with a meal, in an open-label fashion up to Week 148 during late switch phase.

    Investigational medicinal product name
    Dolutegravir Tablets 50 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received dolutegravir tablets 50 mg once daily, with a meal, in an open-label fashion up to Week 148 during late switch phase.

    Arm title
    		 Current antiretroviral regimen
    Arm description
    		 Participants continued to receive their current antiretroviral regimen (two nucleoside reverse transcriptase inhibitors [NRTIs] + a third agent). A third agent included either an: integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). CAR was administered according to the approved labeling in an open-label fashion up to Week 52 during early switch phase. At Week 52, participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) <50 copies per milliliter (c/mL), switched to DTG 50 mg + RPV 25 mg once daily and were followed until Week 148.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Dolutegravir Tablets 50 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received dolutegravir tablets 50 mg once daily, with a meal, in an open-label fashion from Week 52 to Week 148 during late switch phase.

    Investigational medicinal product name
    Rilpivirine Tablets 25 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received rilpivirine tablets 25 mg once daily, with a meal, in an open-label fashion from Week 52 to Week 148 during late Switch phase.

    Number of subjects in period 2
    		DTG + RPV Current antiretroviral regimen
    Started
    239
    238
    Completed
    214
    210
    Not completed
    25
    28
         Consent withdrawn by subject
    7
    5
         Physician decision
    -
    4
         Adverse event, non-fatal
    11
    12
         Lost to follow-up
    -
    1
         Protocol deviation
    3
    3
         Lack of efficacy
    4
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    DTG + RPV
    Reporting group description
    		 Participants received DTG 50 milligrams (mg) + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase. Participants continued to receive DTG 50 mg + RPV 25 mg up to Week 148 during the Late Switch Phase.

    Reporting group title
    Current antiretroviral regimen
    Reporting group description
    		 Participants continued to receive their current antiretroviral regimen (two nucleoside reverse transcriptase inhibitors [NRTIs] + a third agent). A third agent included either an: integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). CAR was administered according to the approved labeling in an open-label fashion up to Week 52 during early switch phase. At Week 52, participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) <50 copies per milliliter (c/mL), switched to DTG 50 mg + RPV 25 mg once daily and were followed until Week 148.

    Reporting group values
    		 DTG + RPV Current antiretroviral regimen Total
    Number of subjects
    		 252 256 508
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 242 246 488
        From 65-84 years
    		 10 10 20
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 43.6 ( 10.93 ) 43.6 ( 10.76 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 58 51 109
        Male
    		 194 205 399
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 3 6 9
        Japanese/East Asian (EA) Heritage (H.)/South EA H.
    		 25 34 59
        Black/African American
    		 24 27 51
        Native Hawaiian or other Pacific Islander
    		 1 0 1
        White
    		 198 188 386
        American Indian or Alaska Native and white
    		 0 1 1
        African American/African H. and Asian
    		 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    DTG + RPV
    Reporting group description
    		 Participants received DTG 50 milligrams (mg) + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase. Participants continued to receive DTG 50 mg + RPV 25 mg up to Week 148 during the Late Switch Phase.

    Reporting group title
    Current antiretroviral regimen
    Reporting group description
    		 Participants continued to receive their current antiretroviral regimen (two nucleoside reverse transcriptase inhibitors [NRTIs] + a third agent). A third agent included either an: integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). CAR was administered according to the approved labeling in an open-label fashion up to Week 52 during early switch phase. At Week 52, participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) <50 copies per milliliter (c/mL), switched to DTG 50 mg + RPV 25 mg once daily and were followed until Week 148.
    Reporting group title
    DTG + RPV
    Reporting group description
    		 Participants received DTG 50 milligrams (mg) + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase. Participants continued to receive DTG 50 mg + RPV 25 mg up to Week 148 during the Late Switch Phase.

    Reporting group title
    Current antiretroviral regimen
    Reporting group description
    		 Participants continued to receive their current antiretroviral regimen (two nucleoside reverse transcriptase inhibitors [NRTIs] + a third agent). A third agent included either an: integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). CAR was administered according to the approved labeling in an open-label fashion up to Week 52 during early switch phase. At Week 52, participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) <50 copies per milliliter (c/mL), switched to DTG 50 mg + RPV 25 mg once daily and were followed until Week 148.

    Subject analysis set title
    DTG 50 mg PK Parameter Population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received DTG 50 mg + RPV 25 mg together once daily, with a meal, in an open-label fashion up to Week 52 during early switch phase. The arm is specific for participants in the PK Parameter Population.

    Subject analysis set title
    RPV 25 mg PK Parameter Population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received DTG 50 mg + RPV 25 mg together once daily, with a meal, in an open-label fashion up to Week 52 during early switch phase. The arm is specific for participants in the PK Parameter Population.

    Subject analysis set title
    CAR-DTG 50 mg LS PK Parameter Population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants from CAR arm received DTG 50 mg + RPV 25 mg together once daily, with a meal, in an open-label fashion from Week 52 to Week 148 during late switch phase. The arm is specific for participants in LS PK Parameter Population.

    Subject analysis set title
    CAR-RPV 25 mg LS PK Parameter Population
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants from CAR arm received DTG 50 mg +RPV 25 mg together once daily, with a meal, in an open-label fashion from Week 52 to Week 148 during late switch phase. The arm is specific for participants in LS PK Parameter Population.

    Subject analysis set title
    DTG 50 mg PK Parameter NNRTI Subset
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received DTG 50 mg + RPV 25 mg together once daily, with a meal, in an open-label fashion up to Week 52 during early switch phase. The arm is specific for participants in PK Parameter NNRTI Subset extra sampling Population.

    Subject analysis set title
    RPV 25 mg PK Parameter NNRTI Subset
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received DTG 50 mg + RPV 25 mg together once daily, with a meal, in an open-label fashion up to Week 52 during early switch phase. The arm is specific for participants in PK Parameter NNRTI Subset extra sampling Population.

    Primary: Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using snapshot algorithm

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    End point title
    		 Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using snapshot algorithm
    End point description
    Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 48 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to demonstrate the non-inferior antiviral activity of switching to DTG + RPV once daily compared to continuation of CAR over 48 weeks in HIV-1 infected antiretroviral therapy (ART)-experienced participants. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for quantitative analysis of HIV-1 RNA. The Intent-to-Treat Exposed (ITT-E) population consisted of all randomly assigned participants who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [1]
    256 [2]
    Units: Percentage of participants
        number (not applicable)
    95
    96
    Notes
    [1] - ITT-E Population
    [2] - ITT-E Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Estimates based on Cochran-Mantel Haenszel stratified analysis adjusting for Baseline stratification factors: Age group (< or >=50 years old) and Baseline third agent (PI, NNRTI, INI).
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    		 [3]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.3
         upper limit
    		 3
    Notes
    [3] - Non-inferiority can be concluded if the lower bound of a two-sided 95% confidence interval for the difference in response rates between the two treatment arms is greater than -10%.

    Secondary: Changes from Baseline in cluster designation (CD)4+ lymphocyte count at Weeks 24 and 48

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    End point title
    		 Changes from Baseline in cluster designation (CD)4+ lymphocyte count at Weeks 24 and 48
    End point description
    Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunological activity of DTG + RPV once daily compared to continuation of CAR. Value obtained at Day 1 was considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 24 and 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [4]
    256 [5]
    Units: Cells per millimeter cube (mm)^3
    arithmetic mean (standard deviation)
        Week 24, n=247, 249
    16.2 ( 150.34 )
    47.4 ( 179.68 )
        Week 48, n=239, 245
    32.3 ( 149.52 )
    41.8 ( 185.53 )
    Notes
    [4] - ITT-E Population
    [5] - ITT-E Population
    No statistical analyses for this end point

    Secondary: Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 24 using snapshot algorithm

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    End point title
    		 Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 24 using snapshot algorithm
    End point description
    Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 24 using the FDA snapshot algorithm was assessed to evaluate the antiviral activity of DTG + RPV once daily compared to continuation of CAR. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for quantitative analysis of HIV-1 RNA.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [6]
    256 [7]
    Units: Percentage of participants
        number (not applicable)
    98
    96
    Notes
    [6] - ITT-E Population
    [7] - ITT-E Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Cochran-Mantel Haenszel stratified analysis adjusting for Baseline stratification factors: Age group (< or >=50 years old) and Baseline third agent (PI, NNRTI, INI). No formal non-inferiority margin has been pre-specified for secondary endpoints.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 4

    Secondary: Number of participants with common non-serious adverse event (AE), any serious AE (SAE), AE of maximum toxicity grade 1, 2, 3 or 4 and AE leading to discontinuation (AELD)

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    End point title
    		 Number of participants with common non-serious adverse event (AE), any serious AE (SAE), AE of maximum toxicity grade 1, 2, 3 or 4 and AE leading to discontinuation (AELD)
    End point description
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a medicinal product, whether or not considered related to medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention were categorized as SAE. AEs were graded as per Division of Acquired Immunodeficiency Syndrome (DAIDS) grading. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. Common AEs were those with >5% incidence for either treatment. This summary presents results as reported after all participants completed the Early Switch Phase.
    End point type
    Secondary
    End point timeframe
    Up to Week 52
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [8]
    256 [9]
    Units: Participants
        Common non-serious AE
    65
    68
        Any SAE
    9
    12
        Maximum Grade 1 AE
    128
    122
        Maximum toxicity Grade 2 AE
    57
    53
        Maximum toxicity Grade 3 AE
    11
    13
        Maximum toxicity Grade 4 AE
    4
    2
        AELD
    9
    2
    Notes
    [8] - Safety Population included all randomized participants who received at least one dose of study drug
    [9] - Safety Population included all randomized participants who received at least one dose of study drug
    No statistical analyses for this end point

    Secondary: Number of participants with maximum post-Baseline emergent chemistry toxicities over 48 weeks

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    End point title
    		 Number of participants with maximum post-Baseline emergent chemistry toxicities over 48 weeks
    End point description
    Blood samples were collected to evaluate alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, blood urea nitrogen (BUN), total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Value obtained at Day 1 was considered as Baseline value. Number of participants who experienced maximum grade toxicity post-Baseline in clinical chemistry over 48 weeks was summarized. Clinical chemistry toxicities were graded using DAIDS grading table for grading severity of adult and pediatric adverse events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. For all laboratory parameters, one assessment out of range was sufficient to be considered a chemistry toxicity.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [10]
    256 [11]
    Units: Participants
        Grade 1
    95
    78
        Grade 2
    61
    86
        Grade 3
    22
    23
        Grade 4
    5
    9
    Notes
    [10] - Safety Population
    [11] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with maximum post-Baseline emergent hematology toxicities over 48 weeks

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    End point title
    		 Number of participants with maximum post-Baseline emergent hematology toxicities over 48 weeks
    End point description
    Blood samples were collected to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, mean corpuscular volume (MCV), red blood cell (RBC) count, white blood cell (WBC) count and platelet count. Value obtained at Day 1 was considered as Baseline value. Number of participants who experienced maximum grade toxicity post-Baseline in hematology over 48 weeks was summarized. Hematology toxicities were graded using DAIDS grading table for grading severity of adult and pediatric adverse events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. For all laboratory parameters, one assessment out of range was sufficient to be considered a hematology toxicity.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [12]
    256 [13]
    Units: Participants
        Grade 1
    11
    11
        Grade 2
    3
    2
        Grade 3
    3
    1
        Grade 4
    0
    1
    Notes
    [12] - Safety Population
    [13] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in high-sensitivity C-reactive protein (hs-CRP) at Week 48

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    End point title
    		 Mean change from Baseline in high-sensitivity C-reactive protein (hs-CRP) at Week 48
    End point description
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess hs-CRP. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    234 [14]
    243 [15]
    Units: mg/ Liter (L)
        arithmetic mean (standard deviation)
    0.11 ( 5.379 )
    0.15 ( 4.944 )
    Notes
    [14] - Safety Population
    [15] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in cystatin C at Week 48

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    End point title
    		 Mean change from Baseline in cystatin C at Week 48
    End point description
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess cystatin C Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    237 [16]
    245 [17]
    Units: mg/L
        arithmetic mean (standard deviation)
    0.00 ( 0.113 )
    -0.01 ( 0.106 )
    Notes
    [16] - Safety Population
    [17] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in D-Dimer at Week 48

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    End point title
    		 Mean change from Baseline in D-Dimer at Week 48
    End point description
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess D-Dimer. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    224 [18]
    238 [19]
    Units: Nanomole/L fibrinogen equivalent units
        arithmetic mean (standard deviation)
    -0.02 ( 2.651 )
    0.02 ( 2.501 )
    Notes
    [18] - Safety Population
    [19] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in fatty acid binding protein 2 (FABP) and soluble CD14 at Week 48

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    End point title
    		 Mean change from Baseline in fatty acid binding protein 2 (FABP) and soluble CD14 at Week 48
    End point description
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess FABP and soluble CD14. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [20]
    256 [21]
    Units: Nanogram/milliliter
    arithmetic mean (standard deviation)
        FABP, n=233, 242
    -2.79 ( 3.007 )
    -1.93 ( 2.150 )
        Soluble CD14, n=234, 242
    379.72 ( 634.053 )
    754.54 ( 656.462 )
    Notes
    [20] - Safety Population
    [21] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in Soluble CD163 and oxidized low density lipoprotein (LDL) at Week 48

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    End point title
    		 Mean change from Baseline in Soluble CD163 and oxidized low density lipoprotein (LDL) at Week 48
    End point description
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess soluble CD163 and oxidized LDL. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [22]
    256 [23]
    Units: Microgram (ug)/Liter
    arithmetic mean (standard deviation)
        Soluble CD163, n=232, 241
    50.18 ( 188.772 )
    54.26 ( 238.900 )
        Oxidized LDL, n=234, 242
    9.49 ( 745.962 )
    -41.30 ( 726.014 )
    Notes
    [22] - Safety Population
    [23] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in retinol binding protein (RBP), serum creatinine and glucose at Week 48

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    End point title
    		 Mean change from Baseline in retinol binding protein (RBP), serum creatinine and glucose at Week 48
    End point description
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess RBP, serum creatinine and glucose. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [24]
    256 [25]
    Units: mg/deciliter (dL)
    arithmetic mean (standard deviation)
        RBP, n=235, 243
    -0.13 ( 1.023 )
    0.03 ( 0.974 )
        Serum creatinine, n=238, 243
    0.087 ( 0.1074 )
    0.011 ( 0.0876 )
        Glucose, n=227, 227
    0.762 ( 13.6194 )
    2.492 ( 12.1674 )
    Notes
    [24] - Safety Population
    [25] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in urine phosphate at Week 48

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    End point title
    		 Mean change from Baseline in urine phosphate at Week 48
    End point description
    Urine biomarker samples were collected at Baseline (Day 1) and Week 48 to assess urine phosphate. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    218 [26]
    224 [27]
    Units: Millimoles (mmol)/ L
        arithmetic mean (standard deviation)
    -1.079 ( 16.9226 )
    -1.511 ( 15.8515 )
    Notes
    [26] - Safety Population
    [27] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in beta-2-microglobulin (B2M) (blood and urine), urine RBP and 25 hydroxy-vitamin D (blood) at Week 48

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    End point title
    		 Mean change from Baseline in beta-2-microglobulin (B2M) (blood and urine), urine RBP and 25 hydroxy-vitamin D (blood) at Week 48
    End point description
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess B2M and 25 hydroxy-vitamin D. Urine samples were collected to assess B2M and RBP. Change from Baseline was calculated as value at indicated time point minus Baseline value. For 25 hydroxy-vitamin D, analysis of changes from Baseline was performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [28]
    256 [29]
    Units: Nanomoles/ L
    arithmetic mean (standard deviation)
        B2M, blood, n=233, 241
    -15.1452 ( 44.55903 )
    -4.5995 ( 38.90474 )
        25 hydroxy-vitamin D, n=235, 244
    -13.9 ( 22.76 )
    -8.2 ( 24.43 )
        Urine B2M, n=89, 96
    -128.2045 ( 726.38825 )
    39.8394 ( 253.43025 )
        Urine RBP, n=221, 231
    -8.8395 ( 28.83977 )
    -0.5851 ( 27.56405 )
    Notes
    [28] - Safety Population
    [29] - Safety Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.007 [30]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [30] - P-value for interaction between treatment group and baseline third agent (25 hydroxy-vitamin D)
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and baseline biomarker level.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.275 [31]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.958
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.888
         upper limit
    		 1.034
    Notes
    [31] - P value to assess difference between treatment groups (25 hydroxy-vitamin D - NNRTI)
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and baseline biomarker level.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.112 [32]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.902
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.793
         upper limit
    		 1.025
    Notes
    [32] - P value to assess difference between treatment groups (25 hydroxy-vitamin D - INI)
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and baseline biomarker level.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.002 [33]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.847
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.763
         upper limit
    		 0.942
    Notes
    [33] - P value to assess difference between treatment groups (25 hydroxy-vitamin D - PI)

    Secondary: Mean change from Baseline in urine albumin/creatinine ratio and urine protein/creatinine ratio at Week 48

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    End point title
    		 Mean change from Baseline in urine albumin/creatinine ratio and urine protein/creatinine ratio at Week 48
    End point description
    Urine biomarker samples were collected at Baseline (Day 1) and Week 48 to assess urine albumin/creatinine ratio and urine protein/creatinine ratio. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [34]
    256 [35]
    Units: Grams (g)/ mol
    arithmetic mean (standard deviation)
        Urine albumin/creatinine ratio, n=166, 171
    -1.19 ( 3.916 )
    -2.59 ( 28.878 )
        urine protein/creatinine ratio, n=176, 182
    -5.63 ( 17.219 )
    -1.43 ( 42.832 )
    Notes
    [34] - Safety Population
    [35] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type I Collagen C-Telopeptides and soluble vascular cell adhesion molecule (sVCAM) at Week 48

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    End point title
    		 Mean change from Baseline in bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type I Collagen C-Telopeptides and soluble vascular cell adhesion molecule (sVCAM) at Week 48
    End point description
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type I Collagen C-Telopeptides and sVCAM. Change from Baseline was calculated as value at indicated time point minus Baseline value. For bone-specific alkaline phosphatase, procollagen 1-N-propeptide, osteocalcin and type 1 collagen C-telopeptide, analyses of changes from baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [36]
    256 [37]
    Units: ug/ L
    arithmetic mean (standard deviation)
        Bone-specific alkaline phosphatase, n=234, 244
    -2.89 ( 4.024 )
    0.90 ( 4.129 )
        Procollagen type 1 N-propeptide, n=234, 242
    -9.1 ( 20.34 )
    -1.4 ( 18.95 )
        Osteocalcin, n=233, 242
    -4.40 ( 7.605 )
    -0.68 ( 6.579 )
        Type I Collagen C-Telopeptides, n=234, 241
    -0.18 ( 0.307 )
    -0.04 ( 1.160 )
        sVCAM, n=234, 243
    -2.21 ( 1291.994 )
    89.07 ( 1239.465 )
    Notes
    [36] - Safety Population
    [37] - Safety Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.001 [38]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [38] - P-value for interaction between treatment group and baseline third agent (bone-specific alkaline phosphatase)
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [39]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.724
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.679
         upper limit
    		 0.772
    Notes
    [39] - P value to assess difference between treatment groups (bone-specific alkaline phosphatase - NNRTI)
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [40]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.825
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.742
         upper limit
    		 0.918
    Notes
    [40] - P value to assess difference between treatment groups (bone-specific alkaline phosphatase - INI)
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [41]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.742
         upper limit
    		 0.884
    Notes
    [41] - P value to assess difference between treatment groups (bone-specific alkaline phosphatase - PI)
    Statistical analysis title
    		 Statistical Analysis 5
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.677 [42]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [42] - P-value for interaction between treatment group and Baseline third agent (procollagen type 1-N-propeptide)
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [43]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.817
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.774
         upper limit
    		 0.863
    Notes
    [43] - P value to assess difference between treatment groups (procollagen type 1-N-propeptide)
    Statistical analysis title
    		 Statistical Analysis 7
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [44]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [44] - P-value for interaction between treatment group and Baseline third agent (osteocalcin)
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [45]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.881
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.823
         upper limit
    		 0.943
    Notes
    [45] - P value to assess difference between treatment groups (osteocalcin - NNRTI)
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.001 [46]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.829
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 0.93
    Notes
    [46] - P value to assess difference between treatment groups (osteocalcin - INI)
    Statistical analysis title
    		 Statistical Analysis 10
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [47]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.691
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.628
         upper limit
    		 0.759
    Notes
    [47] - P value to assess difference between treatment groups (osteocalcin - PI)
    Statistical analysis title
    		 Statistical Analysis 11
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.782 [48]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [48] - P-value for interaction between treatment group and baseline third agent (type 1 collagen cross-linked C-telopeptide)
    Statistical analysis title
    		 Statistical Analysis 12
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for Baseline third agent class, age, sex, BMI category, smoking status and Baseline biomarker level.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [49]
    Method
    		 ANCOVA
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.804
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.742
         upper limit
    		 0.872
    Notes
    [49] - P value to assess difference between treatment groups (type 1 collagen cross-linked C-telopeptide)

    Secondary: Mean change from Baseline in interleukin 6 (IL-6) at Week 48

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    End point title
    		 Mean change from Baseline in interleukin 6 (IL-6) at Week 48
    End point description
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess IL-6. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time point were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    233 [50]
    243 [51]
    Units: Nanograms (ng)/ L
        arithmetic mean (standard deviation)
    0.17 ( 2.736 )
    -0.18 ( 2.944 )
    Notes
    [50] - Safety Population
    [51] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in insulin resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) at Week 48

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    End point title
    		 Mean change from Baseline in insulin resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) at Week 48
    End point description
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess insulin resistance. Change from Baseline was calculated as value at indicated time point minus Baseline value. The homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR) index, the product of basal glucose and insulin levels divided by 22.5 (1,2), is regarded as a simple, inexpensive, and reliable surrogate measure of insulin resistance. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    229 [52]
    237 [53]
    Units: HOMA-IR Score
        arithmetic mean (standard deviation)
    -0.30 ( 5.740 )
    0.51 ( 3.530 )
    Notes
    [52] - Safety Population
    [53] - Safety Population
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in fasting lipids at Weeks 24 and 48

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    End point title
    		 Mean change from Baseline in fasting lipids at Weeks 24 and 48
    End point description
    Blood samples were collected at Baseline (Day 1), Week 24 and Week 48 to assess fasting lipids which included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [54]
    256 [55]
    Units: mmol/ L
    arithmetic mean (standard deviation)
        Total cholesterol, Week 24, n=228, 223
    0.076 ( 0.8398 )
    0.061 ( 0.7368 )
        Total cholesterol, Week 48, n=221, 218
    0.089 ( 0.8488 )
    0.064 ( 0.7197 )
        LDL cholesterol calculation, Week 24, n=224, 217
    0.165 ( 0.7065 )
    0.103 ( 0.6503 )
        LDL cholesterol calculation, Week 48, n=215, 211
    0.108 ( 0.7178 )
    0.029 ( 0.6134 )
        HDL cholesterol direct, Week 24, n=228, 223
    -0.030 ( 0.2601 )
    -0.044 ( 0.2394 )
        HDL cholesterol direct, Week 48, n=221, 218
    0.023 ( 0.2757 )
    0.018 ( 0.2722 )
        Triglycerides, Week 24, n=228, 223
    -0.154 ( 0.7324 )
    -0.001 ( 0.7712 )
        Triglycerides, Week 48, n=221, 218
    -0.093 ( 0.9767 )
    0.046 ( 0.8274 )
    Notes
    [54] - Safety Population
    [55] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with genotypic resistance- Early switch Phase

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    End point title
    		 Number of participants with genotypic resistance- Early switch Phase
    End point description
    Plasma samples were collected for drug resistance testing. Confirmed Virologic Withdrawal (CVW) resistance Population comprised of all participants in the ITT-E Population who met confirmed CVW through the end of visit window (Week 48, Week 100 or Week 148) and had available on-treatment genotypic resistance data at the time CVW criterion was met. Genotypic Resistance data for the following drugs (Rilpivirine [RPV], Dolutegravir [DTG], Emtricitabine [FTC], Tenofovir [TDF], Darunavir/r [DRV/r]) in participants Meeting CVW criteria has been presented. 99999 indicates data was not applicable as the drugs were not received. Genotypic resistance data is only shown for drugs received for Participants Meeting Confirmed Virologic Withdrawal Criteria
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    1 [56]
    1 [57]
    Units: Participants
        NNRTI, RPV, Susceptible
    1
    99999
        NNRTI, RPV, Potential low-level resistance
    0
    99999
        NNRTI, RPV, Low-level resistance
    0
    99999
        NNRTI, RPV, Intermediate resistance
    0
    99999
        NNRTI, RPV, High-level resistance
    0
    99999
        INI, DTG, Susceptible
    1
    99999
        INI, DTG, Potential low-level resistance
    0
    99999
        INI, DTG, Low-level resistance
    0
    99999
        INI, DTG, Intermediate resistance
    0
    99999
        INI, DTG, High-level resistance
    0
    99999
        NRTI, FTC, Susceptible
    99999
    1
        NRTI, FTC, Potential low-level resistance
    99999
    0
        NRTI, FTC, Low-level resistance
    99999
    0
        NRTI, FTC, Intermediate resistance
    99999
    0
        NRTI, FTC, High-level resistance
    99999
    0
        NRTI, TDF, Susceptible
    99999
    1
        NRTI, TDF, Potential low-level resistance
    99999
    0
        NRTI, TDF, Low-level resistance
    99999
    0
        NRTI, TDF, Intermediate resistance
    99999
    0
        NRTI, TDF, High-level resistance
    99999
    0
        PI, DRV/r, Susceptible
    99999
    1
        PI, DRV/r, Potential low-level resistance
    99999
    0
        PI, DRV/r, Low-level resistance
    99999
    0
        PI, DRV/r, Intermediate resistance
    99999
    0
        PI, DRV/r, High-level resistance
    99999
    0
    Notes
    [56] - CVW Resistance Population
    [57] - CVW Resistance Population
    No statistical analyses for this end point

    Secondary: Number of participants with genotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase

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    End point title
    		 Number of participants with genotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase [58]
    End point description
    Plasma samples were collected for drug resistance testing. Genotypic Resistance data for the following drugs (DTG, Elvitegravir [EVG], Raltegravir [RAL], Delavirdine [DLV], Efavirenz [EFV], Etravirine [ETR], Nevirapine [NVP], RPV, Lamivudine [3TC], Abacavir [ABC], FTC, TDF, Zidovudine [ZDV], Stavudine [d4T], Didanosine [ddI], Atazanavir/r [ATV/r], DRV/r, Fosamprenavir/r [FPV/r], Indinavir/r [IDV/r], Lopinavir/r [LPV/r], Nelfinavir [NFV], Ritonavir [RTV], Saquinavir/r [SQV/r], Tipranavir/r [TPV/r]) in participants Meeting Confirmed Virologic Withdrawal Criteria has been presented.
    End point type
    Secondary
    End point timeframe
    Up to Week 148
    Notes
    [58] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 DTG + RPV
    Number of subjects analysed
    5 [59]
    Units: Participants
        INI, DTG, Susceptible
    5
        INI, DTG, Potential low-level resistance
    0
        INI, DTG, Low-level resistance
    0
        INI, DTG, Intermediate resistance
    0
        INI, DTG, High-level resistance
    0
        INI, EVG,Susceptible
    4
        INI, EVG, Potential low-level resistance
    1
        INI, EVG,Low-level resistance
    0
        INI, EVG, Intermediate resistance
    0
        INI, EVG, High-level resistance
    0
        INI, RAL,Susceptible
    4
        INI, RAL, Potential low-level resistance
    1
        INI, RAL, Low-level resistance
    0
        INI, RAL, Intermediate resistance
    0
        INI, RAL, High-level resistance
    0
        NNRTI, DLV, Susceptible
    5
        NNRTI, DLV, Potential low-level resistance
    0
        NNRTI,DLV, Low-level resistance
    0
        NNRTI, DLV, Intermediate resistance
    0
        NNRTI, DLV, High-level resistance
    0
        NNRTI, EFV, Susceptible
    3
        NNRTI, EFV, Potential low-level resistance
    0
        NNRTI, EFV, Low-level resistance
    0
        NNRTI, EFV, Intermediate resistance
    1
        NNRTI, EFV, High-level resistance
    1
        NNRTI, ETR, Susceptible
    3
        NNRTI, ETR, Potential low-level resistance
    1
        NNRTI, ETR, Low-level resistance
    0
        NNRTI, ETR, Intermediate resistance
    1
        NNRTI, ETR, High-level resistance
    0
        NNRTI,NVP, Susceptible
    3
        NNRTI,NVP, Potential low-level resistance
    0
        NNRTI,NVP, Low-level resistance
    0
        NNRTI,NVP, Intermediate resistance
    0
        NNRTI, NVP, High-level resistance
    2
        NNRTI, RPV, Susceptible
    3
        NNRTI, RPV, Potential low-level resistance
    0
        NNRTI, RPV, Low-level resistance
    1
        NNRTI, RPV, Intermediate resistance
    0
        NNRTI, RPV, High-level resistance
    1
        NRTI, 3TC, Susceptible
    5
        NRTI, 3TC, Potential low-level resistance
    0
        NRTI, 3TC, Low-level resistance
    0
        NRTI, 3TC, Intermediate resistance
    0
        NRTI, 3TC, High-level resistance
    0
        NRTI, ABC, Susceptible
    5
        NRTI, ABC, Potential low-level resistance
    0
        NRTI, ABC, Low-level resistance
    0
        NRTI, ABC, Intermediate resistance
    0
        NRTI, ABC, High-level resistance
    0
        NRTI, FTC, Susceptible
    5
        NRTI, FTC, Potential low-level resistance
    0
        NRTI, FTC, Low-level resistance
    0
        NRTI, FTC, Intermediate resistance
    0
        NRTI, FTC, High-level resistance
    0
        NRTI, TDF, Susceptible
    5
        NRTI, TDF, Potential low-level resistance
    0
        NRTI, TDF, Low-level resistance
    0
        NRTI, TDF, Intermediate resistance
    0
        NRTI, TDF, High-level resistance
    0
        NRTI, ZDV, Susceptible
    4
        NRTI, ZDV, Potential low-level resistance
    1
        NRTI, ZDV, Low-level resistance
    0
        NRTI, ZDV, Intermediate resistance
    0
        NRTI, ZDV, High-level resistance
    0
        NRTI, d4T, Susceptible
    4
        NRTI, d4T, Potential low-level resistance
    1
        NRTI, d4T, Low-level resistance
    0
        NRTI, d4T, Intermediate resistance
    0
        NRTI, d4T, High-level resistance
    0
        NRTI, ddI, Susceptible
    5
        NRTI, ddI, Potential low-level resistance
    0
        NRTI, ddI, Low-level resistance
    0
        NRTI, ddI, Intermediate resistance
    0
        NRTI, ddI, High-level resistance
    0
        PI, ATV/r, Susceptible
    5
        PI, ATV/r, Potential low-level resistance
    0
        PI, ATV/r, Low-level resistance
    0
        PI, ATV/r, Intermediate resistance
    0
        PI, ATV/r, High-level resistance
    0
        PI, DRV/r, Susceptible
    5
        PI, DRV/r, Potential low-level resistance
    0
        PI, DRV/r, Low-level resistance
    0
        PI, DRV/r, Intermediate resistance
    0
        PI, DRV/r, High-level resistance
    0
        PI, FPV/r, Susceptible
    5
        PI, FPV/r, Potential low-level resistance
    0
        PI, FPV/r, Low-level resistance
    0
        PI, FPV/r, Intermediate resistance
    0
        PI, FPV/r, High-level resistance
    0
        PI, IDV/r, Susceptible
    5
        PI, IDV/r, Potential low-level resistance
    0
        PI, IDV/r, Low-level resistance
    0
        PI, IDV/r, Intermediate resistance
    0
        PI, IDV/r, High-level resistance
    0
        PI, LPV/r, Susceptible
    5
        PI, LPV/r, Potential low-level resistance
    0
        PI, LPV/r, Low-level resistance
    0
        PI, LPV/r, Intermediate resistance
    0
        PI, LPV/r,High-level resistance
    0
        PI, NFV, Susceptible
    5
        PI, NFV, Potential low-level resistance
    0
        PI, NFV, Low-level resistance
    0
        PI, NFV, Intermediate resistance
    0
        PI, NFV, High-level resistance
    0
        PI, RTV, Susceptible
    5
        PI, RTV, Potential low-level resistance
    0
        PI, RTV, Low-level resistance
    0
        PI, RTV, Intermediate resistance
    0
        PI, RTV, High-level resistance
    0
        PI, SQV/r, Susceptible
    5
        PI, SQV/r, Potential low-level resistance
    0
        PI, SQV/r, Low-level resistance
    0
        PI, SQV/r, Intermediate resistance
    0
        PI, SQV/r, High-level resistance
    0
        PI, TPV/r, Susceptible
    5
        PI, TPV/r, Potential low-level resistance
    0
        PI, TPV/r, Low-level resistance
    0
        PI, TPV/r, Intermediate resistance
    0
        PI, TPV/r, High-level resistance
    0
    Notes
    [59] - CVW resistance Population
    No statistical analyses for this end point

    Secondary: Number of participants with genotypic resistance -CAR Late Switch group through Late Switch Phase

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    End point title
    		 Number of participants with genotypic resistance -CAR Late Switch group through Late Switch Phase
    End point description
    Plasma samples were collected for drug resistance testing. Late Switch (LS) CVW resistance Population comprised of all participants in the LS-ITT-E Population who met CVW through the end of visit window (Week 48, Week 100 or Week 148) and had available on-treatment genotypic resistance data at the time CVW criterion was met. Genotypic Resistance data for the following drugs (DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r) in participants Meeting CVW Criteria has been presented. Only those participants with data available at the specified time point were analyzed.
    End point type
    Secondary
    End point timeframe
    Post-LS Baseline (Week 52) up to Week 148
    End point values
    		 Current antiretroviral regimen
    Number of subjects analysed
    1 [60]
    Units: Participants
        INI, DTG, Susceptible
    1
        INI, DTG, Potential low-level resistance
    0
        INI, DTG, Low-level resistance
    0
        INI, DTG, Intermediate resistance
    0
        INI, DTG, High-level resistance
    0
        INI, EVG,Susceptible
    1
        INI, EVG, Potential low-level resistance
    0
        INI, EVG,Low-level resistance
    0
        INI, EVG, Intermediate resistance
    0
        INI, EVG, High-level resistance
    0
        INI, RAL,Susceptible
    0
        INI, RAL, Potential low-level resistance
    0
        INI, RAL, Low-level resistance
    0
        INI, RAL, Intermediate resistance
    0
        INI, RAL, High-level resistance
    0
        NNRTI, DLV, Susceptible
    1
        NNRTI, DLV, Potential low-level resistance
    0
        NNRTI,DLV, Low-level resistance
    0
        NNRTI, DLV, Intermediate resistance
    0
        NNRTI, DLV, High-level resistance
    0
        NNRTI, EFV, Susceptible
    0
        NNRTI, EFV, Potential low-level resistance
    1
        NNRTI, EFV, Low-level resistance
    0
        NNRTI, EFV, Intermediate resistance
    0
        NNRTI, EFV, High-level resistance
    0
        NNRTI, ETR, Susceptible
    0
        NNRTI, ETR, Potential low-level resistance
    1
        NNRTI, ETR, Low-level resistance
    0
        NNRTI, ETR, Intermediate resistance
    0
        NNRTI, ETR, High-level resistance
    0
        NNRTI,NVP, Susceptible
    0
        NNRTI,NVP, Potential low-level resistance
    1
        NNRTI,NVP, Low-level resistance
    0
        NNRTI,NVP, Intermediate resistance
    0
        NNRTI, NVP, High-level resistance
    0
        NNRTI, RPV, Susceptible
    0
        NNRTI, RPV, Potential low-level resistance
    1
        NNRTI, RPV, Low-level resistance
    0
        NNRTI, RPV, Intermediate resistance
    0
        NNRTI, RPV, High-level resistance
    0
        NRTI, 3TC, Susceptible
    1
        NRTI, 3TC, Potential low-level resistance
    0
        NRTI, 3TC, Low-level resistance
    0
        NRTI, 3TC, Intermediate resistance
    0
        NRTI, 3TC, High-level resistance
    0
        NRTI, ABC, Susceptible
    1
        NRTI, ABC, Potential low-level resistance
    0
        NRTI, ABC, Low-level resistance
    0
        NRTI, ABC, Intermediate resistance
    0
        NRTI, ABC, High-level resistance
    0
        NRTI, FTC, Susceptible
    1
        NRTI, FTC, Potential low-level resistance
    0
        NRTI, FTC, Low-level resistance
    0
        NRTI, FTC, Intermediate resistance
    0
        NRTI, FTC, High-level resistance
    0
        NRTI, TDF, Susceptible
    1
        NRTI, TDF, Potential low-level resistance
    0
        NRTI, TDF, Low-level resistance
    0
        NRTI, TDF, Intermediate resistance
    0
        NRTI, TDF, High-level resistance
    0
        NRTI, ZDV, Susceptible
    1
        NRTI, ZDV, Potential low-level resistance
    0
        NRTI, ZDV, Low-level resistance
    0
        NRTI, ZDV, Intermediate resistance
    0
        NRTI, ZDV, High-level resistance
    0
        NRTI, d4T, Susceptible
    1
        NRTI, d4T, Potential low-level resistance
    0
        NRTI, d4T, Low-level resistance
    0
        NRTI, d4T, Intermediate resistance
    0
        NRTI, d4T, High-level resistance
    0
        NRTI, ddI, Susceptible
    1
        NRTI, ddI, Potential low-level resistance
    0
        NRTI, ddI, Low-level resistance
    0
        NRTI, ddI, Intermediate resistance
    0
        NRTI, ddI, High-level resistance
    0
        PI, ATV/r, Susceptible
    1
        PI, ATV/r, Potential low-level resistance
    0
        PI, ATV/r, Low-level resistance
    0
        PI, ATV/r, Intermediate resistance
    0
        PI, ATV/r, High-level resistance
    0
        PI, DRV/r, Susceptible
    1
        PI, DRV/r, Potential low-level resistance
    0
        PI, DRV/r, Low-level resistance
    0
        PI, DRV/r, Intermediate resistance
    0
        PI, DRV/r, High-level resistance
    0
        PI, FPV/r, Susceptible
    1
        PI, FPV/r, Potential low-level resistance
    0
        PI, FPV/r, Low-level resistance
    0
        PI, FPV/r, Intermediate resistance
    0
        PI, FPV/r, High-level resistance
    0
        PI, IDV/r, Susceptible
    1
        PI, IDV/r, Potential low-level resistance
    0
        PI, IDV/r, Low-level resistance
    0
        PI, IDV/r, Intermediate resistance
    0
        PI, IDV/r, High-level resistance
    0
        PI, LPV/r, Susceptible
    1
        PI, LPV/r, Potential low-level resistance
    0
        PI, LPV/r, Low-level resistance
    0
        PI, LPV/r, Intermediate resistance
    0
        PI, LPV/r,High-level resistance
    0
        PI, NFV, Susceptible
    1
        PI, NFV, Potential low-level resistance
    0
        PI, NFV, Low-level resistance
    0
        PI, NFV, Intermediate resistance
    0
        PI, NFV, High-level resistance
    0
        PI, RTV, Susceptible
    1
        PI, RTV, Potential low-level resistance
    0
        PI, RTV, Low-level resistance
    0
        PI, RTV, Intermediate resistance
    0
        PI, RTV, High-level resistance
    0
        PI, SQV/r, Susceptible
    1
        PI, SQV/r, Potential low-level resistance
    0
        PI, SQV/r, Low-level resistance
    0
        PI, SQV/r, Intermediate resistance
    0
        PI, SQV/r, High-level resistance
    0
        PI, TPV/r, Susceptible
    1
        PI, TPV/r, Potential low-level resistance
    0
        PI, TPV/r, Low-level resistance
    0
        PI, TPV/r, Intermediate resistance
    0
        PI, TPV/r, High-level resistance
    0
    Notes
    [60] - LS CVW resistance Population
    No statistical analyses for this end point

    Secondary: Number of participants with phenotypic resistance-Early switch Phase

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    End point title
    		 Number of participants with phenotypic resistance-Early switch Phase
    End point description
    Plasma samples were collected for drug resistance testing. Phenotypic Resistance data for the following drugs (DTG, RAL, EVG, RPV, ETR, 3TC, ABC, FTC, TDF, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, SQV/r, TPV/r) in participants Meeting CVW Criteria has been presented.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    1 [61]
    1 [62]
    Units: Participants
        INI, DTG, Resistant
    0
    0
        INI, DTG, Partially Sensitive
    0
    0
        INI, DTG, Sensitive
    1
    1
        INI, EVG, Resistant
    0
    0
        INI, EVG, Sensitive
    1
    1
        INI, RAL, Resistant
    0
    0
        INI, RAL, Sensitive
    1
    1
        NNRTI, DLV, Resistant
    0
    0
        NNRTI, DLV, Sensitive
    1
    1
        NNRTI, EFV, Resistant
    0
    0
        NNRTI, EFV, Sensitive
    1
    1
        NNRTI, ETR, Resistant
    0
    0
        NNRTI, ETR, Partially Sensitive
    0
    0
        NNRTI, ETR, Sensitive
    1
    1
        NNRTI, NVP, Resistant
    0
    0
        NNRTI, NVP, Sensitive
    1
    1
        NNRTI, RPV, Resistant
    0
    0
        NNRTI, RPV, Sensitive
    1
    1
        NRTI, 3TC, Resistant
    0
    0
        NRTI, 3TC, Sensitive
    1
    1
        NRTI, ABC, Resistant
    0
    0
        NRTI, ABC, Partially Sensitive
    0
    0
        NRTI, ABC, Sensitive
    1
    1
        NRTI,FTC, Resistant
    0
    0
        NRTI, FTC, Sensitive
    1
    1
        NRTI, TDF, Resistant
    0
    0
        NRTI, TDF, Partially Sensitive
    0
    0
        NRTI, TDF, Sensitive
    1
    1
        NRTI, ZDV, Resistant
    0
    0
        NRTI, ZDV, Sensitive
    1
    1
        NRTI, d4T, Resistant
    0
    0
        NRTI, d4T, Sensitive
    1
    1
        NRTI, ddI, Resistant
    0
    0
        NRTI, ddI, Partially Sensitive
    0
    0
        NRTI, ddI, Sensitive
    1
    1
        PI, ATV/r, Resistant
    0
    0
        PI, ATV/r, Sensitive
    1
    1
        PI, DRV/r, Resistant
    0
    0
        PI, DRV/r, Partially Sensitive
    0
    0
        PI, DRV/r, Sensitive
    1
    1
        PI, FPV/r, Resistant
    0
    0
        PI, FPV/r, Partially Sensitive
    0
    0
        PI, FPV/r, Sensitive
    1
    1
        PI, IDV/r, Resistant
    0
    0
        PI, IDV/r, Sensitive
    1
    1
        PI, LPV/r, Resistant
    0
    0
        PI, LPV/r, Partially Sensitive
    0
    0
        PI, LPV/r, Sensitive
    1
    1
        PI, NFV, Resistant
    0
    0
        PI, NFV, Sensitive
    1
    1
        PI, RTV, Resistant
    0
    0
        PI, RTV, Sensitive
    1
    1
        PI, SQV/r, Resistant
    0
    0
        PI, SQV/r, Partially Sensitive
    0
    0
        PI, SQV/r, Sensitive
    1
    1
        PI, TPV/r, Resistant
    0
    0
        PI, TPV/r, Partially Sensitive
    0
    0
        PI, TPV/r, Sensitive
    1
    1
    Notes
    [61] - CVW Resistance Population
    [62] - CVW Resistance Population
    No statistical analyses for this end point

    Secondary: Number of participants with phenotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase

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    End point title
    		 Number of participants with phenotypic resistance-DTG+RPV early switch group through Early and Late Switch Phase [63]
    End point description
    Plasma samples were collected for drug resistance testing. Phenotypic Resistance data for the following drugs (DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r) in participants Meeting CVW Criteria has been presented.
    End point type
    Secondary
    End point timeframe
    Up to Week 148
    Notes
    [63] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 DTG + RPV
    Number of subjects analysed
    5 [64]
    Units: Participants
        INI, DTG, Resistant
    0
        INI, DTG, Partially Sensitive
    0
        INI, DTG, Sensitive
    5
        INI, EVG, Resistant
    0
        INI, EVG, Partially Sensitive
    0
        INI, EVG, Sensitive
    5
        INI, RAL, Resistant
    0
        INI, RAL, Partially Sensitive
    0
        INI, RAL, Sensitive
    5
        NNRTI, DLV, Resistant
    1
        NNRTI, DLV, Partially Sensitive
    0
        NNRTI, DLV, Sensitive
    4
        NNRTI, EFV, Resistant
    1
        NNRTI, EFV, Partially Sensitive
    0
        NNRTI, EFV, Sensitive
    4
        NNRTI, ETR, Resistant
    0
        NNRTI, ETR, Partially Sensitive
    1
        NNRTI, ETR, Sensitive
    4
        NNRTI, NVP, Resistant
    1
        NNRTI, NVP, Partially Sensitive
    0
        NNRTI, NVP, Sensitive
    4
        NNRTI, RPV, Resistant
    1
        NNRTI, RPV, Partially Sensitive
    0
        NNRTI, RPV, Sensitive
    4
        NRTI, 3TC, Resistant
    0
        NRTI, 3TC, Partially Sensitive
    0
        NRTI, 3TC, Sensitive
    5
        NRTI, ABC, Resistant
    0
        NRTI, ABC, Partially Sensitive
    0
        NRTI, ABC, Sensitive
    5
        NRTI, FTC, Resistant
    0
        NRTI, FTC, Partially Sensitive
    0
        NRTI, FTC, Sensitive
    5
        NRTI, TDF, Resistant
    0
        NRTI, TDF, Partially Sensitive
    0
        NRTI, TDF, Sensitive
    5
        NRTI, ZDV, Resistant
    0
        NRTI, ZDV, Partially Sensitive
    0
        NRTI, ZDV, Sensitive
    5
        NRTI, d4T, Resistant
    0
        NRTI, d4T, Partially Sensitive
    0
        NRTI, d4T, Sensitive
    5
        NRTI, ddI, Resistant
    0
        NRTI, ddI, Partially Sensitive
    0
        NRTI, ddI, Sensitive
    5
        PI, ATV/r, Resistant
    0
        PI, ATV/r, Partially Sensitive
    0
        PI, ATV/r, Sensitive
    5
        PI, DRV/r, Resistant
    0
        PI, DRV/r, Partially Sensitive
    0
        PI, DRV/r, Sensitive
    5
        PI, FPV/r, Resistant
    0
        PI, FPV/r, Partially Sensitive
    0
        PI, FPV/r, Sensitive
    5
        PI, IDV/r, Resistant
    0
        PI, IDV/r, Partially Sensitive
    0
        PI, IDV/r, Sensitive
    5
        PI, LPV/r, Resistant
    0
        PI, LPV/r, Partially Sensitive
    0
        PI, LPV/r, Sensitive
    5
        PI, NFV, Resistant
    0
        PI, NFV, Partially Sensitive
    0
        PI, NFV, Sensitive
    5
        PI, RTV, Resistant
    0
        PI, RTV, Partially Sensitive
    0
        PI, RTV, Sensitive
    5
        PI, SQV/r, Resistant
    0
        PI, SQV/r, Partially Sensitive
    0
        PI, SQV/r, Sensitive
    5
        PI, TPV/r, Resistant
    0
        PI, TPV/r, Partially Sensitive
    0
        PI, TPV/r, Sensitive
    5
    Notes
    [64] - CVW resistance Population
    No statistical analyses for this end point

    Secondary: Number of participants with phenotypic resistance-CAR Late Switch group through Late Switch Phase

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    End point title
    		 Number of participants with phenotypic resistance-CAR Late Switch group through Late Switch Phase
    End point description
    Plasma samples were collected for drug resistance testing. Phenotypic Resistance data for the following drugs (DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r) in participants Meeting CVW Criteria has been presented. Only those participants with data available at the specified time point were analyzed.
    End point type
    Secondary
    End point timeframe
    Post-LS Baseline (Week 52) up to Week 148
    End point values
    		 Current antiretroviral regimen
    Number of subjects analysed
    1 [65]
    Units: Participants
        NNRTI, DLV, Resistant
    1
        NNRTI, DLV, Partially Sensitive
    0
        NNRTI, DLV, Sensitive
    0
        NNRTI, EFV, Resistant
    1
        NNRTI, EFV, Partially Sensitive
    0
        NNRTI, EFV, Sensitive
    0
        NNRTI, ETR, Resistant
    0
        NNRTI, ETR, Partially Sensitive
    0
        NNRTI, ETR, Sensitive
    1
        NNRTI, NVP, Resistant
    1
        NNRTI, NVP, Partially Sensitive
    0
        NNRTI, NVP, Sensitive
    0
        NNRTI, RPV, Resistant
    0
        NNRTI, RPV, Partially Sensitive
    0
        NNRTI, RPV, Sensitive
    1
        NRTI, 3TC, Resistant
    0
        NRTI, 3TC, Partially Sensitive
    0
        NRTI, 3TC, Sensitive
    1
        NRTI, ABC, Resistant
    0
        NRTI, ABC, Partially Sensitive
    0
        NRTI, ABC, Sensitive
    1
        NRTI, FTC, Resistant
    0
        NRTI, FTC, Partially Sensitive
    0
        NRTI, FTC, Sensitive
    1
        NRTI, TDF, Resistant
    0
        NRTI, TDF, Partially Sensitive
    0
        NRTI, TDF, Sensitive
    1
        NRTI, ZDV, Resistant
    0
        NRTI, ZDV, Partially Sensitive
    0
        NRTI, ZDV, Sensitive
    1
        NRTI, d4T, Resistant
    0
        NRTI, d4T, Partially Sensitive
    0
        NRTI, d4T, Sensitive
    1
        NRTI, ddI, Resistant
    0
        NRTI, ddI, Partially Sensitive
    0
        NRTI, ddI, Sensitive
    1
        PI, ATV/r, Resistant
    0
        PI, ATV/r, Partially Sensitive
    0
        PI, ATV/r, Sensitive
    1
        PI, DRV/r, Resistant
    0
        PI, DRV/r, Partially Sensitive
    0
        PI, DRV/r, Sensitive
    1
        PI, FPV/r, Resistant
    0
        PI, FPV/r, Partially Sensitive
    0
        PI, FPV/r, Sensitive
    1
        PI, IDV/r, Resistant
    0
        PI, IDV/r, Partially Sensitive
    0
        PI, IDV/r, Sensitive
    1
        PI, LPV/r, Resistant
    0
        PI, LPV/r, Partially Sensitive
    0
        PI, LPV/r, Sensitive
    1
        PI, NFV, Resistant
    0
        PI, NFV, Partially Sensitive
    0
        PI, NFV, Sensitive
    1
        PI, RTV, Resistant
    0
        PI, RTV, Partially Sensitive
    0
        PI, RTV, Sensitive
    1
        PI, SQV/r, Resistant
    0
        PI, SQV/r, Partially Sensitive
    0
        PI, SQV/r, Sensitive
    1
        PI, TPV/r, Resistant
    0
        PI, TPV/r, Partially Sensitive
    0
        PI, TPV/r, Sensitive
    1
    Notes
    [65] - LS CVW resistance Population
    No statistical analyses for this end point

    Secondary: Pre-dose concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 in participants switching to DTG + RPV -DTG+RPV early switch group through Early and Late Switch Phase

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    End point title
    		 Pre-dose concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 in participants switching to DTG + RPV -DTG+RPV early switch group through Early and Late Switch Phase
    End point description
    Two separate blood samples for DTG and RPV were collected pre-dose at Weeks 4, 24, 48, 56, 76, and 100. Pre-dose concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 is summarized for the participants switching to DTG + RPV in the early + late switch phase. Pharmacokinetic (PK) Parameter Population consisted of all participants who received DTG +RPV and provided at least one evaluable estimate of predose concentration (C0). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Pre-dose at Week 4, 24, 48, 56, 76 and 100
    End point values
    		 DTG 50 mg PK Parameter Population RPV 25 mg PK Parameter Population
    Number of subjects analysed
    243 [66]
    243 [67]
    Units: ug/ L
    arithmetic mean (standard deviation)
        Week 4, n=130, 130
    1581.06 ( 1146.860 )
    92.05 ( 138.288 )
        Week 24, n=210, 210
    1835.68 ( 1120.539 )
    87.88 ( 39.141 )
        Week 48, n=215, 211
    1915.11 ( 1304.238 )
    95.18 ( 48.228 )
        Week 56, n=204, 204
    1872.65 ( 1173.815 )
    95.38 ( 53.602 )
        Week 76, n=194,194
    1711.83 ( 1092.143 )
    88.10 ( 42.250 )
        Week 100, n=203, 203
    1854.17 ( 1197.958 )
    92.38 ( 44.604 )
    Notes
    [66] - PK Parameter Population
    [67] - PK Parameter Population
    No statistical analyses for this end point

    Secondary: Pre-dose concentrations of DTG and RPV at Weeks 56, 76 and 100 in participants switching to DTG+RPV - CAR Late Switch group through Late Switch Phase

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    End point title
    		 Pre-dose concentrations of DTG and RPV at Weeks 56, 76 and 100 in participants switching to DTG+RPV - CAR Late Switch group through Late Switch Phase
    End point description
    Two separate blood samples for DTG and RPV were collected pre-dose at Weeks 56, 76, and 100. Pre-dose concentrations of DTG and RPV at Weeks 56, 76 and 100 is summarized for the participants switching to DTG + RPV in the late switch phase. LS PK Parameter Population comprised of all participants who were randomized to CAR and received DTG + RPV in the Late Switch Phase and provided at least one evaluable estimate of Pre-dose concentration. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Pre-dose at Weeks 56, 76 and 100
    End point values
    		 CAR-DTG 50 mg LS PK Parameter Population CAR-RPV 25 mg LS PK Parameter Population
    Number of subjects analysed
    225 [68]
    225 [69]
    Units: ug/ L
    arithmetic mean (standard deviation)
        Week 56, n=198, 198
    1738.55 ( 1329.931 )
    84.14 ( 47.290 )
        Week 76, n=192, 192
    1800.39 ( 1162.370 )
    97.79 ( 52.532 )
        Week 100, n=192, 191
    1907.20 ( 1235.676 )
    101.93 ( 63.296 )
    Notes
    [68] - LS PK Parameter Population
    [69] - LS PK Parameter Population
    No statistical analyses for this end point

    Secondary: Pre-dose concentrations of DTG and RPV at Weeks 2, 4 and 8 in the first 20 participants who switch from efavirenz (EFV) or nevirapine (NVP) to DTG + RPV

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    End point title
    		 Pre-dose concentrations of DTG and RPV at Weeks 2, 4 and 8 in the first 20 participants who switch from efavirenz (EFV) or nevirapine (NVP) to DTG + RPV
    End point description
    Two blood samples were collected pre-dose for DTG and RPV at Weeks 2,4 and 8 only for the first 20 participants who switch from EFV or NVP to DTG + RPV. One blood sample was collected pre-dose for EFV or NVP at Week 2 for the first 20 participants who switch from EFV or NVP to DTG + RPV. PK Parameter NNRTI Subset Extra Sampling Population consisted of the first approximately 20 participants in the PK Parameter NNRTI Subset population who have extra PK samples at weeks 2, 4 and 8. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Pre-dose at Week 2, 4 and 8
    End point values
    		 DTG 50 mg PK Parameter NNRTI Subset RPV 25 mg PK Parameter NNRTI Subset
    Number of subjects analysed
    26 [70]
    26 [71]
    Units: ug/ L
    arithmetic mean (standard deviation)
        Week 2, n=16, 15
    821.25 ( 574.607 )
    65.360 ( 31.2965 )
        Week 4, n=19, 19
    994.00 ( 581.201 )
    67.374 ( 27.5663 )
        Week 8, n=19, 19
    1561.34 ( 1096.381 )
    77.416 ( 37.7129 )
    Notes
    [70] - PK Parameter NNRTI Subset extra sampling Population
    [71] - PK Parameter NNRTI Subset extra sampling Population
    No statistical analyses for this end point

    Secondary: Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 48 using snapshot algorithm by Baseline third agent treatment class

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    End point title
    		 Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 48 using snapshot algorithm by Baseline third agent treatment class
    End point description
    Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 48 using the FDA snapshot algorithm was assessed by Baseline third agent class to assess the impact of Baseline third agent class (INI, NNRTI, or PI) on efficacy of DTG +RPV compared to continuation of CAR. Plasma samples were collected for quantitative analysis of HIV-1 RNA. The analysis was done using Cochran-Mantel Haenszel test stratified by current antiretroviral third-agent class and age group. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [72]
    256 [73]
    Units: Percentage of participants
    number (not applicable)
        NNRTI, n=131, 134
    95
    98
        INI, n=46, 48
    98
    96
        PI, n=75, 74
    95
    92
    Notes
    [72] - ITT-E Population
    [73] - ITT-E Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.317 [74]
    Method
    		 Chi-squared corrected
    Confidence interval
    Notes
    [74] - One-sided p-value from weighted least squares chi-squared statistic. A p-value <=0.10 was used to indicate statistically significant evidence of heterogeneity in the difference in proportions across levels of each analysis strata.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    NNRTI: No formal non-inferiority margin has been pre-specified for secondary endpoints.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -3.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.7
         upper limit
    		 1.5
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    INI: No formal non-inferiority margin has been pre-specified for secondary endpoints.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.1
         upper limit
    		 9
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    PI: No formal non-inferiority margin has been pre-specified for secondary endpoints.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.3
         upper limit
    		 10.8

    Secondary: Changes from Baseline in cluster designation (CD)4+ lymphocyte count at Week 48 by Baseline third agent treatment class

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    End point title
    		 Changes from Baseline in cluster designation (CD)4+ lymphocyte count at Week 48 by Baseline third agent treatment class
    End point description
    Blood samples were collected and CD4 cell count assessment by flow cytometry was carried out to assess the impact of Baseline third agent class (INI, NNRTI, or PI) on efficacy, safety and tolerability of DTG +RPV compared to continuation of CAR. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [75]
    256 [76]
    Units: Cells per mm^3
    arithmetic mean (standard deviation)
        NNRTI, n=124, 130
    47.9 ( 142.90 )
    25.0 ( 151.27 )
        INI, n=45, 46
    19.9 ( 148.63 )
    39.9 ( 200.38 )
        PI, n=70, 69
    12.5 ( 160.27 )
    74.7 ( 227.78 )
    Notes
    [75] - ITT-E Population
    [76] - ITT-E Population
    No statistical analyses for this end point

    Secondary: Number of participants with any AE, AELD or AE with grade 1, 2, 3 or 4 toxicity over 48 weeks by Baseline third agent treatment class

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    End point title
    		 Number of participants with any AE, AELD or AE with grade 1, 2, 3 or 4 toxicity over 48 weeks by Baseline third agent treatment class
    End point description
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any AE, AELD or AE with maximum grade toxicity experienced by any one participant over 48 weeks by Baseline third agent class (INI, NNRTI, or PI) was summarized. AEs were graded using DAIDS grading table for grading severity of adult and pediatric adverse events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [77]
    256 [78]
    Units: Participants
        Any AE, NNRTI, n=131, 134
    102
    98
        Any AE, INI, n=46, 48
    38
    34
        Any AE, PI, n=75, 74
    60
    58
        NNRTI, Maximum toxicity Grade 1 AE, n=131, 134
    69
    72
        NNRTI, Maximum toxicity Grade 2 AE, n=131, 134
    27
    23
        NNRTI, Maximum toxicity Grade 3 AE, n=131, 134
    5
    2
        NNRTI, Maximum toxicity Grade 4 AE, n=131, 134
    1
    1
        INI, Maximum toxicity Grade 1 AE, n=46, 48
    28
    20
        INI, Maximum toxicity Grade 2 AE, n=46, 48
    7
    12
        INI, Maximum toxicity Grade 3 AE, n=46, 48
    2
    2
        INI, Maximum toxicity Grade 4 AE, n=46, 48
    1
    0
        PI, Maximum toxicity Grade 1 AE, n=75, 74
    31
    30
        PI, Maximum toxicity Grade 2 AE, n=75, 74
    23
    18
        PI, Maximum toxicity Grade 3 AE, n=75, 74
    4
    9
        PI, Maximum toxicity Grade 4 AE, n=75, 74
    2
    1
        AELD, NNRTI, n=131, 134
    3
    0
        AELD, INI, n=46, 48
    2
    0
        AELD, PI, n=75, 74
    4
    2
    Notes
    [77] - Safety Population
    [78] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with maximum post-baseline emergent chemistry toxicities over 48 weeks by Baseline third agent treatment class

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    End point title
    		 Number of participants with maximum post-baseline emergent chemistry toxicities over 48 weeks by Baseline third agent treatment class
    End point description
    Blood samples were collected to evaluate ALT, albumin, ALP, AST, total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, BUN, total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Value at Day 1 was considered as Baseline. Number of participants who experienced maximum toxicity grade post-Baseline in chemistry parameters over 48 weeks by Baseline third agent treatment class (INI, NNRTI, PI) was summarized. Clinical chemistry toxicities were graded using DAIDS grading table for grading severity of adult and pediatric adverse events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [79]
    256 [80]
    Units: Participants
        NNRTI, Grade 1, n=131, 134
    47
    42
        NNRTI, Grade 2, n=131, 134
    32
    48
        NNRTI, Grade 3, n=131, 134
    13
    13
        NNRTI, Grade 4, n=131, 134
    2
    3
        INI, Grade 1, n= 46, 48
    13
    11
        INI, Grade 2, n= 46, 48
    19
    15
        INI, Grade 3, n= 46, 48
    1
    1
        INI, Grade 4, n= 46, 48
    3
    2
        PI, Grade 1, n= 75, 74
    35
    25
        PI, Grade 2, n= 75, 74
    10
    23
        PI, Grade 3, n= 75, 74
    8
    9
        PI, Grade 4, n= 75, 74
    0
    4
    Notes
    [79] - Safety Population
    [80] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with maximum post-Baseline emergent hematology toxicities over 48 weeks by Baseline third agent treatment class

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    End point title
    		 Number of participants with maximum post-Baseline emergent hematology toxicities over 48 weeks by Baseline third agent treatment class
    End point description
    Blood samples were collected to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, MCV, RBC count, WBC count and platelet count. Value at Day 1 was considered as Baseline. Number of participants who experienced maximum toxicity grade post-Baseline in hematology parameters over 48 weeks by Baseline third agent treatment class (INSTI, NNRTI, PI) was summarized. Hematology toxicities were graded using DAIDS grading table for grading severity of adult and pediatric adverse events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [81]
    256 [82]
    Units: Participants
        NNRTI; Grade 1; n= 131, 134
    5
    3
        NNRTI; Grade 2; n= 131, 134
    1
    1
        NNRTI; Grade 3; n= 131, 134
    1
    1
        NNRTI; Grade 4; n= 131, 134
    0
    1
        INI; Grade 1; n= 46, 48
    2
    2
        INI; Grade 2; n= 46, 48
    1
    0
        INI; Grade 3; n= 46, 48
    0
    0
        INI; Grade 4; n= 46, 48
    0
    0
        PI; Grade 1; n= 75, 74
    4
    6
        PI; Grade 2; n= 75, 74
    1
    1
        PI; Grade 3; n= 75, 74
    2
    0
        PI; Grade 4; n= 75, 74
    0
    0
    Notes
    [81] - Safety Population
    [82] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with observed genotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class

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    End point title
    		 Number of participants with observed genotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class
    End point description
    For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain genotype data on as many samples as possible. Samples for drug resistance testing (genotypic) were to be collected at Day 1. Number of participants with genotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome has not been analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    0 [83]
    0 [84]
    Units: Participants
    Notes
    [83] - CVW Resistance Population
    [84] - CVW Resistance Population
    No statistical analyses for this end point

    Secondary: Number of participants with observed phenotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class

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    End point title
    		 Number of participants with observed phenotypic resistance for participants meeting virologic withdrawal criteria by Baseline third agent treatment class
    End point description
    For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain phenotype data on as many samples as possible. Samples for drug resistance testing (phenotypic) were to be collected at Day 1. Number of participants with phenotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome was not analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    0 [85]
    0 [86]
    Units: Participants
    Notes
    [85] - CVW Resistance Population
    [86] - CVW Resistance Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in fasting lipids at Weeks 24 and 48 by Baseline third agent treatment class

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    End point title
    		 Change from Baseline in fasting lipids at Weeks 24 and 48 by Baseline third agent treatment class
    End point description
    Blood samples were collected at Baseline (Day 1), Weeks 24 and 48 to assess fasting lipids which included total cholesterol (CHO), LDL cholesterol, HDL cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value. 99999 indicates data was not available due to insufficient number of participants to analyze the data. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [87]
    256 [88]
    Units: mmol/ mL
    arithmetic mean (standard deviation)
        CHO, Week 24, overall, n=228, 223
    3.239 ( 18.1556 )
    2.375 ( 14.8357 )
        CHO, Week 48, overall, n=221, 218
    3.596 ( 18.7072 )
    2.472 ( 14.7202 )
        CHO, Week 24, NNRTI, n=0, 118
    99999 ( 99999 )
    3.383 ( 13.3685 )
        CHO, Week 48, NNRTI, n=0, 118
    99999 ( 99999 )
    4.099 ( 13.8992 )
        CHO, Week 24, INI, n=0, 44
    99999 ( 99999 )
    1.288 ( 14.8933 )
        CHO, Week 48, INI, n=0, 43
    99999 ( 99999 )
    0.524 ( 15.3143 )
        CHO, Week 24, PI, n=0, 61
    99999 ( 99999 )
    1.211 ( 17.3972 )
        CHO, Week 48, PI, n=0, 57
    99999 ( 99999 )
    0.575 ( 15.7475 )
        HDL CHO direct, Overall, Week 24, n=228, 223
    0.017 ( 18.7575 )
    -2.478 ( 16.6754 )
        HDL CHO direct, Overall, Week 48, n=221, 218
    3.975 ( 21.1039 )
    3.095 ( 18.8909 )
        HDL CHO direct, NNRTI, Week 24, n=0, 118
    99999 ( 99999 )
    0.062 ( 15.9300 )
        HDL CHO direct, NNRTI, Week 48, n=0, 118
    99999 ( 99999 )
    4.818 ( 16.2253 )
        HDL CHO direct, INI, Week 24, n=0, 44
    99999 ( 99999 )
    -4.968 ( 16.2973 )
        HDL CHO direct, INI, Week 48, n=0, 43
    99999 ( 99999 )
    0.539 ( 22.6496 )
        HDL CHO direct, PI, Week 24, n=0, 61
    99999 ( 99999 )
    -5.594 ( 17.7923 )
        HDL CHO direct, PI, Week 48, n=0, 57
    99999 ( 99999 )
    1.457 ( 20.8346 )
        LDL CHO calculation, Overall, Week 24, n=224, 217
    11.504 ( 36.9087 )
    6.196 ( 24.0104 )
        LDL CHO calculation, Overall, Week 48, n=215, 211
    8.257 ( 33.0405 )
    3.258 ( 22.3644 )
        LDL CHO calculation, NNRTI, Week 24, n=0, 116
    99999 ( 99999 )
    6.816 ( 20.9081 )
        LDL CHO calculation, NNRTI, Week 48, n=0, 114
    99999 ( 99999 )
    4.920 ( 20.9300 )
        LDL CHO calculation, INI, Week 24, n=0, 44
    99999 ( 99999 )
    6.355 ( 24.1747 )
        LDL CHO calculation, INI, Week 48, n=0, 43
    99999 ( 99999 )
    3.490 ( 23.3198 )
        LDL CHO calculation, PI, Week 24, n=0, 57
    99999 ( 99999 )
    4.813 ( 29.5705 )
        LDL CHO calculation, PI, Week 48, n=0, 54
    99999 ( 99999 )
    -0.434 ( 24.4332 )
        Triglycerides, Overall, Week 24, n=228, 223
    0.096 ( 55.6357 )
    8.649 ( 48.8249 )
        Triglycerides, Overall, Week 48, n=221, 218
    3.605 ( 54.4914 )
    11.068 ( 54.6321 )
        Triglycerides, NNRTI, Week 24, n=0, 118
    99999 ( 99999 )
    6.867 ( 44.8605 )
        Triglycerides, NNRTI, Week 48, n=0, 118
    99999 ( 99999 )
    10.215 ( 58.4055 )
        Triglycerides, INI, Week 24, n=0, 44
    99999 ( 99999 )
    8.386 ( 54.1265 )
        Triglycerides, INI, Week 48, n=0, 43
    99999 ( 99999 )
    4.644 ( 48.8708 )
        Triglycerides, PI, Week 24, n=0, 61
    99999 ( 99999 )
    12.283 ( 52.6943 )
        Triglycerides, PI, Week 48, n=0, 57
    99999 ( 99999 )
    17.681 ( 50.6912 )
    Notes
    [87] - Safety Population
    [88] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 4, 24 and 48-Early Switch Phase

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    End point title
    		 Change from Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 4, 24 and 48-Early Switch Phase
    End point description
    Symptom Distress Module, also called HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in participant. Symptom count is sum of number of symptoms present and ranges from 0(none) to 20(all). Symptom bother score is based on score for each symptom present ranging from 1(it doesn't bother me) to 4(it bothers me a lot). Symptom bother score is unweighted sum of the bother item scores for each symptom and ranges from 0(minimum) to 80(maximum). Last observation carried forward (LOCF) was used as primary method of analysis. Change from Baseline was calculated as value at indicated time point minus Baseline value. Day 1 was considered as Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles)
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 4, Week 24 and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [89]
    256 [90]
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Symptom count, Week 4, n=212, 197
    -1.6 ( 4.19 )
    0.2 ( 4.26 )
        Symptom count, Week 24, n=214, 201
    -0.8 ( 5.19 )
    -0.2 ( 4.06 )
        Symptom count, Week 48, n=214, 201
    -0.4 ( 5.52 )
    0.0 ( 4.49 )
        Symptom Bother Score, Week 4, n=212, 197
    -3.0 ( 7.25 )
    -0.8 ( 7.82 )
        Symptom Bother Score, Week 24, n=214, 201
    -1.7 ( 8.47 )
    -1.3 ( 8.53 )
        Symptom Bother Score, Week 48, n=214, 201
    -1.4 ( 8.32 )
    -0.7 ( 9.03 )
    Notes
    [89] - ITT-E Population
    [90] - ITT-E Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.94 [91]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [91] - P-value for interaction between treatment group and Baseline symptom bother score (Week 4)
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for age, Baseline third agent, gender, race and Baseline score.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [92]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.924
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.26
         upper limit
    		 -1.588
    Notes
    [92] - P value to assess difference between treatment groups (Week 4)
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.001 [93]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [93] - P-value for interaction between treatment group and Baseline symptom bother score (Week 24)
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for age, Baseline third agent, gender, race and Baseline score.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.11 [94]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.192
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.656
         upper limit
    		 0.271
    Notes
    [94] - P value to assess difference between treatment groups (Week 24)
    Statistical analysis title
    		 Statistical Analysis 5
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.048 [95]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [95] - P-value for interaction between treatment group and Baseline symptom bother score (Week 48)
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Estimates are calculated from an ANCOVA model adjusting for age, Baseline third agent, gender, race and Baseline score.
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.038 [96]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.569
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.048
         upper limit
    		 -0.09
    Notes
    [96] - P value to assess difference between treatment groups (Week 48)

    Secondary: Change from Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 56, 76, 100 and 148-DTG+RPV early switch group through Early and Late Switch Phase

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    End point title
    		 Change from Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 56, 76, 100 and 148-DTG+RPV early switch group through Early and Late Switch Phase [97]
    End point description
    Symptom Distress Module, also called the HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in participant. Symptom count is the sum of number of symptoms present and ranges from 0 (none) to 20 (all). Symptom bother score is based on score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). Symptom bother score is unweighted sum of the bother item scores for each symptom. Symptom bother score ranges from 0 (minimum bother score) to 80 (maximum bother score). LOCF was used as primary method of analysis. Change from Baseline was calculated as value at indicated time point minus Baseline value. Day 1 was considered as Baseline value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 56, Week 76, Week 100 and Week 148
    Notes
    [97] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 DTG + RPV
    Number of subjects analysed
    214 [98]
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Symptom count, Week 56
    -0.9 ( 4.99 )
        Symptom count, Week 76
    -0.2 ( 5.42 )
        Symptom count, Week 100
    -0.4 ( 5.08 )
        Symptom count, Week 148
    -0.6 ( 5.24 )
        Symptom Bother Score, Week 56
    -1.6 ( 8.52 )
        Symptom Bother Score, Week 76
    -0.9 ( 8.84 )
        Symptom Bother Score, Week 100
    -0.8 ( 8.71 )
        Symptom Bother Score, Week 148
    -0.8 ( 9.15 )
    Notes
    [98] - ITT-E Population
    No statistical analyses for this end point

    Secondary: Change from LS Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 56, 76, 100 and 148 - CAR Late Switch group through Late Switch Phase

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    End point title
    		 Change from LS Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 56, 76, 100 and 148 - CAR Late Switch group through Late Switch Phase
    End point description
    Symptom Distress Module, also called HIV Symptom Index or Symptoms Impact Questionnaire is a 20-item self-reported measure that addresses presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in participant. Symptom count is sum of symptoms present and ranges from 0(none) to 20(all). Symptom bother score is based on score for each symptom present ranging from 1(it doesn't bother me) to 4(it bothers me a lot). Symptom bother score is unweighted sum of bother item scores for each symptom and ranges from 0(minimum) to 80(maximum). Last observation carried forward (LOCF) was used as primary method of analysis. Change from LS Baseline was calculated as value at indicated time point minus LS Baseline value. Value at Week 48 was considered as LS Baseline value. Only participants with data available at specified time points were analyzed (represented by n=X in the category titles)
    End point type
    Secondary
    End point timeframe
    LS Baseline (Week 48), Week 56, Week 76, Week 100 and Week 148
    End point values
    		 Current antiretroviral regimen
    Number of subjects analysed
    238 [99]
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Symptom count, Week 56, n=186
    -0.7 ( 4.38 )
        Symptom count, Week 76, n=188
    0.1 ( 4.19 )
        Symptom count, Week 100, n=188
    0.0 ( 4.35 )
        Symptom count, Week 148, n=188
    0.4 ( 4.92 )
        Symptom Bother Score, Week 56, n=186
    -2.0 ( 8.11 )
        Symptom Bother Score, Week 76, n=188
    -0.4 ( 8.33 )
        Symptom Bother Score, Week 100, n=188
    -0.4 ( 9.17 )
        Symptom Bother Score, Week 148, n=188
    0.7 ( 9.57 )
    Notes
    [99] - LS ITT-E Population
    No statistical analyses for this end point

    Secondary: Change from Baseline treatment satisfaction using the HIV treatment satisfaction questionnaire (HIV TSQ) at Weeks 4, 24 and 48-Early Switch Phase

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    End point title
    		 Change from Baseline treatment satisfaction using the HIV treatment satisfaction questionnaire (HIV TSQ) at Weeks 4, 24 and 48-Early Switch Phase
    End point description
    HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 (very dissatisfied, inconvenient) to 6 (very satisfied, convenient). The items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscale scores: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). Higher scores indicated greater treatment satisfaction as compared to the past few weeks. The HIV TSQ was administered as a paper questionnaire. Total score, lifestyle/ease score and General satisfaction/CS have been summarized. LOCF was used as primary method of analysis. Value obtained at Day 1 was considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 4, Week 24 and Week 48
    End point values
    		 DTG + RPV Current antiretroviral regimen
    Number of subjects analysed
    252 [100]
    256 [101]
    Units: Scores on a scale
    median (full range (min-max))
        Total score, Week 4, n=250, 249
    0.0 (-16 to 33)
    0.0 (-25 to 21)
        Total score, Week 24, n=252, 254
    1.0 (-18 to 33)
    0.0 (-28 to 28)
        Total score, Week 48, n=252, 254
    0.5 (-24 to 33)
    0.0 (-28 to 20)
        lifestyle/ease Sub-score, Week 4, n=248, 249
    0.0 (-7 to 15)
    0.0 (-9 to 13)
        lifestyle/ease Sub-score, Week 24, n=252, 254
    0.0 (-11 to 15)
    0.0 (-14 to 12)
        lifestyle/ease Sub-score, Week 48, n=252, 254
    0.0 (-13 to 16)
    0.0 (-14 to 13)
        General Satisfaction/CS, Week 4, n=249, 249
    0.0 (-10 to 18)
    0.0 (-16 to 13)
        General Satisfaction/CS, Week 24, n=252, 254
    0.0 (-7 to 18)
    0.0 (-14 to 17)
        General Satisfaction/CS, Week 48, n=252, 254
    0.0 (-14 to 18)
    0.0 (-14 to 10)
    Notes
    [100] - ITT-E Population
    [101] - ITT-E Population
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.002 [102]
    Method
    		 Wilcoxon rank sum test
    Confidence interval
    Notes
    [102] - P-value to assess HIVTSQs Total Score difference between treatment groups (Week 4)
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [103]
    Method
    		 Wilcoxon rank sum test
    Confidence interval
    Notes
    [103] - P-value to assess HIVTSQs Total Score difference between treatment groups (Week 24)
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.024 [104]
    Method
    		 Wilcoxon rank sum test
    Confidence interval
    Notes
    [104] - P-value to assess HIVTSQs Total score difference between treatment groups (Week 48)
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [105]
    Method
    		 Wilcoxon rank sum test
    Confidence interval
    Notes
    [105] - P-value to assess HIVTSQs lifestyle/ease sub- score difference between treatment groups (Week 4)
    Statistical analysis title
    		 Statistical Analysis 5
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001 [106]
    Method
    		 Wilcoxon rank sum test
    Confidence interval
    Notes
    [106] - P-value to assess HIVTSQs lifestyle/ease sub- score difference between treatment groups (Week 24)
    Statistical analysis title
    		 Statistical Analysis 6
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.005 [107]
    Method
    		 Wilcoxon rank sum test
    Confidence interval
    Notes
    [107] - P-value to assess HIVTSQs lifestyle/ease sub- score difference between treatment groups (Week 48)
    Statistical analysis title
    		 Statistical Analysis 7
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.063 [108]
    Method
    		 Wilcoxon rank sum test
    Confidence interval
    Notes
    [108] - P-value to assess HIVTSQs General satisfaction/CS sub- score difference between treatment groups (Week 4)
    Statistical analysis title
    		 Statistical Analysis 8
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.002 [109]
    Method
    		 Wilcoxon rank sum test
    Confidence interval
    Notes
    [109] - P-value to assess HIVTSQs General satisfaction/CS sub- score difference between treatment groups (Week 24)
    Statistical analysis title
    		 Statistical Analysis 9
    Comparison groups
    DTG + RPV v Current antiretroviral regimen
    Number of subjects included in analysis
    508
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.099 [110]
    Method
    		 Wilcoxon rank sum test
    Confidence interval
    Notes
    [110] - P-value to assess HIVTSQs General satisfaction/CS sub- score difference between treatment groups (Week 48)

    Secondary: Change from Baseline treatment satisfaction using HIV TSQ at Weeks 56, 76, 100 and 148 - DTG+RPV early switch group through Early and Late Switch Phase

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    End point title
    		 Change from Baseline treatment satisfaction using HIV TSQ at Weeks 56, 76, 100 and 148 - DTG+RPV early switch group through Early and Late Switch Phase [111]
    End point description
    HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 (very dissatisfied, inconvenient) to 6 (very satisfied, convenient). The items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscale scores: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). Higher scores indicated greater treatment satisfaction as compared to the past few weeks. The HIV TSQ was administered as a paper questionnaire. Total score, lifestyle/ease score and General satisfaction/CS have been summarized. LOCF was used as primary method of analysis. Value obtained at Day 1 was considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 56, Week 76, Week 100 and Week 148
    Notes
    [111] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 DTG + RPV
    Number of subjects analysed
    252 [112]
    Units: Scores on a scale
    median (full range (min-max))
        Total score, Week 56
    0.0 (-42 to 33)
        Total score, Week 76
    0.5 (-35 to 33)
        Total score, Week 100
    0.0 (-17 to 33)
        Total score, Week 148
    1.0 (-23 to 32)
        Lifestyle/ease Sub-score, Week 56
    0.0 (-23 to 16)
        Lifestyle/ease Sub-score, Week 76
    0.0 (-19 to 16)
        Lifestyle/ease Sub-score, Week 100
    0.0 (-13 to 16)
        Lifestyle/ease Sub-score, Week 148
    0.0 (-13 to 15)
        General Satisfaction/CS, Week 56
    0.0 (-19 to 18)
        General Satisfaction/CS, Week 76
    0.0 (-16 to 17)
        General Satisfaction/CS, Week 100
    0.0 (-13 to 17)
        General Satisfaction/CS, Week 148
    0.0 (-12 to 17)
    Notes
    [112] - ITT-E Population
    No statistical analyses for this end point

    Secondary: Change from LS Baseline treatment satisfaction using HIV TSQ at Weeks 56, 76, 100 and 148 - CAR Late Switch group through Late Switch Phase

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    End point title
    		 Change from LS Baseline treatment satisfaction using HIV TSQ at Weeks 56, 76, 100 and 148 - CAR Late Switch group through Late Switch Phase
    End point description
    HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 (very dissatisfied, inconvenient) to 6 (very satisfied, convenient). The items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscale scores: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). Higher scores indicated greater treatment satisfaction as compared to the past few weeks. The HIV TSQ was administered as a paper questionnaire. Total score, lifestyle/ease score and General satisfaction/CS have been summarized. LOCF was used as primary method of analysis. Value obtained at Week 48 was considered as LS Baseline value. Change from LS Baseline was calculated as value at indicated time point minus LS Baseline value. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    LS Baseline (Week 48), Week 56, Week 76, Week 100 and Week 148
    End point values
    		 Current antiretroviral regimen
    Number of subjects analysed
    236 [113]
    Units: Scores on a scale
    median (full range (min-max))
        Total score, Week 56
    0.0 (-31 to 31)
        Total score, Week 76
    0.0 (-37 to 31)
        Total score, Week 100
    0.0 (-37 to 26)
        Total score, Week 148
    0.0 (-37 to 26)
        Lifestyle/ease Sub-score, Week 56
    0.0 (-14 to 16)
        Lifestyle/ease Sub-score, Week 76
    0.0 (-21 to 16)
        Lifestyle/ease Sub-score, Week 100
    0.0 (-21 to 18)
        Lifestyle/ease Sub-score, Week 148
    0.0 (-21 to 16)
        General Satisfaction/CS, Week 56
    0.0 (-17 to 16)
        General Satisfaction/CS, Week 76
    0.0 (-17 to 16)
        General Satisfaction/CS, Week 100
    0.0 (-17 to 14)
        General Satisfaction/CS, Week 148
    0.0 (-17 to 13)
    Notes
    [113] - LS ITT-E Population
    No statistical analyses for this end point

    Other pre-specified: Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 using the Snapshot algorithm-DTG+RPV early switch group through Early and Late Switch Phase

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    End point title
    		 Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 using the Snapshot algorithm-DTG+RPV early switch group through Early and Late Switch Phase [114]
    End point description
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with plasma HIV 1 RNA < 50 c/mL using the FDA snapshot algorithm was assessed. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest.
    End point type
    Other pre-specified
    End point timeframe
    Weeks 100 and 148
    Notes
    [114] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 DTG + RPV
    Number of subjects analysed
    252 [115]
    Units: Percentage of participants
    number (not applicable)
        Week 100
    88
        Week 148
    85
    Notes
    [115] - ITT-E Population
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline in CD4+ lymphocyte count at Weeks 100 and 148-DTG+RPV early switch group through Early and Late Switch Phase

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    End point title
    		 Change from Baseline in CD4+ lymphocyte count at Weeks 100 and 148-DTG+RPV early switch group through Early and Late Switch Phase [116]
    End point description
    Blood samples were collected for CD4+ cell count assessment by flow cytometry. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Day 1), Weeks 100 and 148
    Notes
    [116] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 DTG + RPV
    Number of subjects analysed
    252 [117]
    Units: Cells/mm^3
    arithmetic mean (standard deviation)
        Week 100; n=224
    25.1 ( 156.31 )
        Week 148; n=212
    39.9 ( 174.40 )
    Notes
    [117] - ITT-E Population
    No statistical analyses for this end point

    Other pre-specified: Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 using the Snapshot algorithm-CAR Late Switch group through Late Switch Phase

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    End point title
    		 Percentage of participants with plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 using the Snapshot algorithm-CAR Late Switch group through Late Switch Phase
    End point description
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with plasma HIV 1 RNA < 50 c/mL using the FDA snapshot algorithm was assessed. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest.
    End point type
    Other pre-specified
    End point timeframe
    Weeks 100 and 148
    End point values
    		 Current antiretroviral regimen
    Number of subjects analysed
    238 [118]
    Units: Percentage of participants
    number (not applicable)
        Week 100
    90
        Week 148
    87
    Notes
    [118] - LS ITT-E Population
    No statistical analyses for this end point

    Other pre-specified: Change from LS Baseline in CD4+ lymphocyte count at Weeks 100 and 148-CAR Late Switch group through Late Switch Phase

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    End point title
    		 Change from LS Baseline in CD4+ lymphocyte count at Weeks 100 and 148-CAR Late Switch group through Late Switch Phase
    End point description
    Blood samples were collected for CD4+ cell count assessment by flow cytometry. Change from LS Baseline was calculated as value at indicated time point minus LS Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
    End point type
    Other pre-specified
    End point timeframe
    LS Baseline (Week 48), Weeks 100 and 148
    End point values
    		 Current antiretroviral regimen
    Number of subjects analysed
    238 [119]
    Units: Cells/mm^3
    arithmetic mean (standard deviation)
        Week 100; n=217
    -3.3 ( 180.82 )
        Week 148; n=207
    3.7 ( 205.29 )
    Notes
    [119] - LS ITT-E Population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Data presented for DTG+RPV (Early Switch) and CAR (Early Switch) represent safety events up to Week 52. Data for DTG+RPV (Early+Late Switch) represents safety events up to Week 148 and CAR (Late Switch) represents safety events from Week 52 to Week 148.
    Adverse event reporting additional description
    On treatment SAEs and non-serious AEs were reported for the Safety Population for DTG+RPV (Early Switch), CAR (Early Switch) and DTG+RPV (Early+Late Switch). LS Safety Population was used for CAR (Late Switch arm).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    DTG + RPV (Early Switch)
    Reporting group description
    		 Participants received DTG 50 milligrams (mg) + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase.

    Reporting group title
    CAR (Early Switch)
    Reporting group description
    		 Participants continued to receive their current antiretroviral regimen (two nucleoside reverse transcriptase inhibitors [NRTIs] + a third agent). A third agent included either an: integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). CAR was administered according to the approved labeling in an open-label fashion up to Week 52 during early switch phase.

    Reporting group title
    DTG + RPV (Early + Late Switch)
    Reporting group description
    		 Participants received DTG 50 mg + RPV 25 mg together once daily at approximately the same time, with a meal, in an open-label fashion up to Week 52 during early switch phase. Participants continued to receive DTG 50 mg + RPV 25 mg up to Week 148 during the Late Switch Phase.

    Reporting group title
    CAR (Late Switch)
    Reporting group description
    		 At Week 52, participants who received CAR during the early switch phase, with HIV-1 RNA <50 c/mL, switched to DTG 50 mg + RPV 25 mg once daily and were followed until Week 148.

    Serious adverse events
    		 DTG + RPV (Early Switch) CAR (Early Switch) DTG + RPV (Early + Late Switch) CAR (Late Switch)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 252 (3.97%)
    13 / 256 (5.08%)
    34 / 252 (13.49%)
    22 / 238 (9.24%)
         number of deaths (all causes)
    0
    1
    1
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Hodgkin's disease mixed cellularity stage unspecified
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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 / 1
    0 / 0
    0 / 0
    Plasmablastic lymphoma
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anogenital warts
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine carcinoma
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oropharyngeal squamous cell carcinoma
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural neoplasm
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Testicular germ cell tumour mixed
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Death
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Panic attack
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Wrist fracture
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural pneumothorax
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wolff-Parkinson-White syndrome
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Toxic encephalopathy
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Syncope
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Anal fistula
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Pancreatitis acute
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Drug-induced liver injury
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Thyroid mass
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Influenza
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Peritonsillar abscess
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Pneumonia
         subjects affected / exposed
    1 / 252 (0.40%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Thyroglossal cyst infection
         subjects affected / exposed
    0 / 252 (0.00%)
    1 / 256 (0.39%)
    0 / 252 (0.00%)
    0 / 238 (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
    Hepatitis A
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    3 / 252 (1.19%)
    3 / 238 (1.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute hepatitis B
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shigella infection
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    0 / 252 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal osteomyelitis
         subjects affected / exposed
    0 / 252 (0.00%)
    0 / 256 (0.00%)
    1 / 252 (0.40%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 DTG + RPV (Early Switch) CAR (Early Switch) DTG + RPV (Early + Late Switch) CAR (Late Switch)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    107 / 252 (42.46%)
    102 / 256 (39.84%)
    167 / 252 (66.27%)
    134 / 238 (56.30%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    24 / 252 (9.52%)
    17 / 256 (6.64%)
    37 / 252 (14.68%)
    23 / 238 (9.66%)
         occurrences all number
    25
    19
    43
    29
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    9 / 252 (3.57%)
    3 / 256 (1.17%)
    13 / 252 (5.16%)
    6 / 238 (2.52%)
         occurrences all number
    9
    3
    14
    6
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    22 / 252 (8.73%)
    17 / 256 (6.64%)
    35 / 252 (13.89%)
    19 / 238 (7.98%)
         occurrences all number
    24
    18
    38
    20
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 252 (1.19%)
    9 / 256 (3.52%)
    10 / 252 (3.97%)
    13 / 238 (5.46%)
         occurrences all number
    3
    9
    10
    13
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    9 / 252 (3.57%)
    6 / 256 (2.34%)
    18 / 252 (7.14%)
    18 / 238 (7.56%)
         occurrences all number
    10
    6
    20
    20
    Depression
         subjects affected / exposed
    10 / 252 (3.97%)
    2 / 256 (0.78%)
    17 / 252 (6.75%)
    5 / 238 (2.10%)
         occurrences all number
    10
    2
    18
    6
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    8 / 252 (3.17%)
    19 / 256 (7.42%)
    25 / 252 (9.92%)
    18 / 238 (7.56%)
         occurrences all number
    9
    20
    28
    19
    Pain in extremity
         subjects affected / exposed
    9 / 252 (3.57%)
    5 / 256 (1.95%)
    18 / 252 (7.14%)
    12 / 238 (5.04%)
         occurrences all number
    9
    6
    19
    16
    Arthralgia
         subjects affected / exposed
    8 / 252 (3.17%)
    4 / 256 (1.56%)
    14 / 252 (5.56%)
    17 / 238 (7.14%)
         occurrences all number
    10
    5
    17
    19
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    27 / 252 (10.71%)
    31 / 256 (12.11%)
    52 / 252 (20.63%)
    39 / 238 (16.39%)
         occurrences all number
    33
    35
    84
    55
    Syphilis
         subjects affected / exposed
    8 / 252 (3.17%)
    7 / 256 (2.73%)
    27 / 252 (10.71%)
    20 / 238 (8.40%)
         occurrences all number
    10
    7
    39
    24
    Upper respiratory tract infection
         subjects affected / exposed
    7 / 252 (2.78%)
    10 / 256 (3.91%)
    26 / 252 (10.32%)
    17 / 238 (7.14%)
         occurrences all number
    9
    11
    32
    25
    Influenza
         subjects affected / exposed
    4 / 252 (1.59%)
    12 / 256 (4.69%)
    12 / 252 (4.76%)
    13 / 238 (5.46%)
         occurrences all number
    4
    13
    12
    16
    Bronchitis
         subjects affected / exposed
    7 / 252 (2.78%)
    4 / 256 (1.56%)
    16 / 252 (6.35%)
    11 / 238 (4.62%)
         occurrences all number
    7
    5
    19
    14
    Urinary tract infection
         subjects affected / exposed
    9 / 252 (3.57%)
    2 / 256 (0.78%)
    13 / 252 (5.16%)
    3 / 238 (1.26%)
         occurrences all number
    9
    2
    13
    3

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Feb 2015
    Protocol was amended to include additional pharmacokinetic visits for the first 20 participants in the non-nucleoside reverse transcriptase inhibitor (NNRTI) subset who switch from Efavirenz (EFV) or Nevirapine (NVP) in the early switch phase and additional pharmacokinetic visits for all participants in the late switch phase, addition of stratification by planned participation in the dual-energy x-ray absorptiometry (DEXA) substudy, revisions to inclusion and exclusion criteria, revision to the definition of study completion, edits to the time and events table, revisions to suicidal risk monitoring section, and minor clarifications and corrections of typographical errors.
    08 Jun 2015
    Protocol was amended to include reasons for switch for Protease inhibitor (PI)-class aligned with other Antiretroviral therapy (ART) class switches, revisions to stratified analysis of the primary endpoint, revisions to virologic withdrawal criteria, references to study drug versus investigational product , and minor clarifications and corrections of typographical errors.
    27 Feb 2018
    Protocol was amended to include the introduction of commercially derived supplies of Dolutegravir (DTG) as IP; included statements to clarify that in Taiwan and Russia, the Symptoms Distress Module is not utilized as no validated translations are available. Two editorial revisions were made to aid clarity and correct a typographical error.
    03 Jul 2018
    Changes were made to the protocol to manage and mitigate risks following identification of a potential safety issue related to neural tube defect in infants born to women with exposure to dolutegravir at the time of conception. The description of the dolutegravir and rilpivirine Investigator’s brochures were updated to the current version. - The Risk Assessment table was updated to include language regarding risk and mitigation of neural tube defects. - Inclusion criterion number 5 was updated to exclude the double barrier method of contraception, which does not meet updated GlaxoSmithKline (GSK)/ViiV criteria for a highly effective method. Acceptable methods of contraception were clarified. - The Withdrawal Criteria were updated to include a reminder that females of reproductive potential who change their minds and desire to be pregnant or who do not wish to comply with the approved pregnancy avoidance methods, should also be withdrawn from the study. - The Time and Events Table. was updated to include a reminder for investigators to check at every visit that females of reproductive potential are avoiding pregnancy. - The References was revised to update the references for the dolutegravir Investigator’s Brochure and the rilpivirine Investigator’s Brochure to the current versions, and to include a new reference citing methods of highly effective contraception.
    10 Sep 2019
    Changes were made to the protocol applicable only in the Russian Federation. This country-specific amendment was to facilitate treatment of participants recruited in the Russian Federation with the DTG/RPV fixed dose combination (FDC) tablet to satisfy a regulatory requirement for data of participants recruited locally who have received the DTG/RPV FDC. The reference section was updated to include the current versions of the dolutegravir Investigator’s Brochure and the rilpivirine Investigator’s Brochure.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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