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    Clinical Trial Results:
    A Phase III, randomized, multicenter, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of switching to dolutegravir plus lamivudine in HIV-1 infected adults who are virologically suppressed

    Summary
    EudraCT number
    		 2015-004401-17
    Trial protocol
    		 DE   GB   ES   BE   NL  
    Global end of trial date

    Results information
    Results version number
    		 v1
    This version publication date
    02 May 2020
    First version publication date
    02 May 2020
    Other versions
    		 v2 , v3 , v4 , v5 , v6

    Trial information

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    Trial identification
    Sponsor protocol code
    204862
    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, ViiV Healthcare, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, ViiV Healthcare, 1 8664357343, GSKClinicalSupportHD@gsk.com
    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
    06 Aug 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 May 2019
    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 DTG +3TC once daily compared to continuation of TBR over 48 weeks in HIV-1 infected, ART therapy (ART)-experienced, virologically suppressed participants.
    Protection of trial subjects
    Not Applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Jan 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 40
    Country: Number of subjects enrolled
    Belgium: 25
    Country: Number of subjects enrolled
    Canada: 25
    Country: Number of subjects enrolled
    France: 26
    Country: Number of subjects enrolled
    Germany: 83
    Country: Number of subjects enrolled
    Japan: 11
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    Spain: 229
    Country: Number of subjects enrolled
    United States: 286
    Country: Number of subjects enrolled
    United Kingdom: 13
    Worldwide total number of subjects
    743
    EEA total number of subjects
    381
    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)
    726
    From 65 to 84 years
    17
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This non-inferiority study evaluated antiviral activity of switching to dolutegravir (DTG) + lamivudine (3TC) fixed dose combination (FDC) once daily compared to continuation of a Tenofovir alafenamide (TAF)-based regimen (TBR) over 48 weeks in virologically suppressed participants with human immunodeficiency type 1 infection.

    Pre-assignment
    Screening details
    		 743 participants were enrolled, of which two participants did not receive treatment and hence 741 participants received at least one treatment into the study. The results presented are based on Week 48 primary analysis.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 DTG+3TC FDC
    Arm description
    		 Participants who were on a stable TBR and who had an HIV-1 ribonucleic acid (RNA) <50 copies per millilter (c/mL) at the time of screening, received fixed dose combination of DTG 50 milligrams (mg) + 3TC 300 mg once daily up to 48 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dolutegravir (DTG)+Lamivudine (3TC) fixed dose combination (FDC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received DTG 50 milligrams (mg) + 3TC 300 mg FDC as a white, oval and film-coated tablet. The tablets were packed in high density polyethylene (HDPE) bottles with induction seals, 2 grams (gm) desiccant, and child resistant closures. Each 60 milliliter (mL) bottle contains 30 tablets.

    Arm title
    		 TAF-based regimen
    Arm description
    		 Participants who were on a stable TBR and who had an HIV-1 RNA<50 c/mL at the time of screening, were continued to receive TBR up to 48 weeks. One participant randomized to the TBR arm received TDF (tenofovir disoproxil) rather than TAF-and was presented within the “TAF-based regimen” arm for efficacy because the efficacy of TAF and TDF are comparable. However the participant was presented separately under “TDF-based regimen” for Safety because the safety profiles of TDF and TAF differ.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Tenofovir alafenamide (TAF) based regimen (TBR)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants continued to receive stable TBR

    Number of subjects in period 1 [1]
    		DTG+3TC FDC TAF-based regimen
    Started
    369
    372
    Completed
    0
    0
    Not completed
    369
    372
         Consent withdrawn by subject
    7
    16
         Physician decision
    1
    1
         Adverse event, non-fatal
    13
    2
         Ongoing at the time of interim analysis
    342
    343
         Lost to follow-up
    3
    5
         Protocol deviation
    3
    2
         Lack of efficacy
    -
    3
    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: Two participants out of the total number of participants enrolled did not receive treatment.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    DTG+3TC FDC
    Reporting group description
    		 Participants who were on a stable TBR and who had an HIV-1 ribonucleic acid (RNA) <50 copies per millilter (c/mL) at the time of screening, received fixed dose combination of DTG 50 milligrams (mg) + 3TC 300 mg once daily up to 48 weeks.

    Reporting group title
    TAF-based regimen
    Reporting group description
    		 Participants who were on a stable TBR and who had an HIV-1 RNA<50 c/mL at the time of screening, were continued to receive TBR up to 48 weeks. One participant randomized to the TBR arm received TDF (tenofovir disoproxil) rather than TAF-and was presented within the “TAF-based regimen” arm for efficacy because the efficacy of TAF and TDF are comparable. However the participant was presented separately under “TDF-based regimen” for Safety because the safety profiles of TDF and TAF differ.

    Reporting group values
    		 DTG+3TC FDC TAF-based regimen Total
    Number of subjects
    		 369 372 741
    Age categorical
    Units: Subjects
        All Participants
    		 369 372 741
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 40.6 ( 10.76 ) 40.9 ( 11.54 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 25 33 58
        Male
    		 344 339 683
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 7 8 15
        Asian-Central/South Asian Heritage (H)
    		 3 4 7
        Asian-Japanese H/East Asian H/South East Asian H
    		 10 9 19
        Black or African American
    		 50 58 108
        Native Hawaiian or other Pacific Islander
    		 1 3 4
        White-Arabic/North African (NA) H
    		 5 2 7
        White-Arabic/NA H and white/caucasia/European H
    		 0 1 1
        White-White/caucasian/European H
    		 292 286 578
        Asian and White
    		 0 1 1
        Black or African American and White
    		 1 0 1
    Baseline third agent
    Blood samples were collected to evaluate Baseline third agents including non-nucleoside reverse transcriptase inhibitors (NNRTI), integrase strand transfer inhibitors (INSTI) and protease inhibitors (PI) based on the antiretroviral medications taken at Baseline.
    Units: Subjects
        NNRTI
    		 51 48 99
        INSTI
    		 289 296 585
        Protease Inhibiitors
    		 29 28 57
    HIV infection by Centers for Disease Control and Prevention (CDC) classification
    CDC classification for human immunodeficiency (HIV) were: Stage 1: No acquired immuno deficiency syndrome (AIDS) defining condition and CD4+ T-lymphocyte count: >=500 cells per microliter (cells/mcL); Stage 2: No AIDS infection and CD4+ lymphocyte count: 200-499 cell/mcL and Stage 3: with HIV infection and CD4+ T-lymphocye count <200 cells/mcL.
    Units: Subjects
        HIV infection Stage 1
    		 255 259 514
        HIV infection Stage 2
    		 94 94 188
        HIV infection Stage 3
    		 20 19 39
    Cluster of differentiation 4 plus (CD4+) cell count
    Blood samples were collected to evaluate Baseline CD4+ cell count using flow cytometry. Median along with first and third quartiles are presented for Baseline CD4+ count.
    Units: Cells per cubic millimeter (cells/mm^3)
        median (inter-quartile range (Q1-Q3))
    		 682.0 (492.0 to 862.0) 720.0 (531.5 to 901.5) -
    Subject analysis sets

    Subject analysis set title
    Randomized to TBR but received TDF-based regimen
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participant randomized to TBR arm who had HIV-1 RNA <50 c/mL at the time of screening, received TDF-based regimen instead of TAF-based regimen in error. Participant continued to receive TDF-regimen up to the Week 48 visit (participant withdrew from the study at Week 36)

    Subject analysis sets values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects
    1
    Age categorical
    Units: Subjects
        All Participants
    1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    ( )
    Sex: Female, Male
    Units: Participants
        Female
        Male
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
        Asian-Central/South Asian Heritage (H)
        Asian-Japanese H/East Asian H/South East Asian H
        Black or African American
        Native Hawaiian or other Pacific Islander
        White-Arabic/North African (NA) H
        White-Arabic/NA H and white/caucasia/European H
        White-White/caucasian/European H
        Asian and White
        Black or African American and White
    Baseline third agent
    Blood samples were collected to evaluate Baseline third agents including non-nucleoside reverse transcriptase inhibitors (NNRTI), integrase strand transfer inhibitors (INSTI) and protease inhibitors (PI) based on the antiretroviral medications taken at Baseline.
    Units: Subjects
        NNRTI
        INSTI
        Protease Inhibiitors
    HIV infection by Centers for Disease Control and Prevention (CDC) classification
    CDC classification for human immunodeficiency (HIV) were: Stage 1: No acquired immuno deficiency syndrome (AIDS) defining condition and CD4+ T-lymphocyte count: >=500 cells per microliter (cells/mcL); Stage 2: No AIDS infection and CD4+ lymphocyte count: 200-499 cell/mcL and Stage 3: with HIV infection and CD4+ T-lymphocye count <200 cells/mcL.
    Units: Subjects
        HIV infection Stage 1
        HIV infection Stage 2
        HIV infection Stage 3
    Cluster of differentiation 4 plus (CD4+) cell count
    Blood samples were collected to evaluate Baseline CD4+ cell count using flow cytometry. Median along with first and third quartiles are presented for Baseline CD4+ count.
    Units: Cells per cubic millimeter (cells/mm^3)
        median (inter-quartile range (Q1-Q3))

    End points

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    End points reporting groups
    Reporting group title
    DTG+3TC FDC
    Reporting group description
    		 Participants who were on a stable TBR and who had an HIV-1 ribonucleic acid (RNA) <50 copies per millilter (c/mL) at the time of screening, received fixed dose combination of DTG 50 milligrams (mg) + 3TC 300 mg once daily up to 48 weeks.

    Reporting group title
    TAF-based regimen
    Reporting group description
    		 Participants who were on a stable TBR and who had an HIV-1 RNA<50 c/mL at the time of screening, were continued to receive TBR up to 48 weeks. One participant randomized to the TBR arm received TDF (tenofovir disoproxil) rather than TAF-and was presented within the “TAF-based regimen” arm for efficacy because the efficacy of TAF and TDF are comparable. However the participant was presented separately under “TDF-based regimen” for Safety because the safety profiles of TDF and TAF differ.

    Subject analysis set title
    Randomized to TBR but received TDF-based regimen
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participant randomized to TBR arm who had HIV-1 RNA <50 c/mL at the time of screening, received TDF-based regimen instead of TAF-based regimen in error. Participant continued to receive TDF-regimen up to the Week 48 visit (participant withdrew from the study at Week 36)

    Primary: Percentage of participants with virologic failure endpoint as per Food and Drug Administration (FDA) snapshot category at Week 48

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    End point title
    		 Percentage of participants with virologic failure endpoint as per Food and Drug Administration (FDA) snapshot category at Week 48
    End point description
    Percentage of participants with virologic failure (plasma HIV-1 RNA >=50 c/mL) was evaluated using FDA snapshot algorithm at Week 48. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. Intent-to-treat exposed (ITT-E) Population comprises of all randomized participants who receive at least one dose of study treatment either DTG + 3TC or TBR. Participants were assessed according to the treatment to which the participant was randomized. Any participant receiving a treatment randomization number was considered to be randomized. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable.
    End point type
    Primary
    End point timeframe
    Week 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [1]
    372 [2]
    Units: Percentage of participants
        number (not applicable)
    0.3
    0.5
    Notes
    [1] - ITT-E Population.
    [2] - ITT-E Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    ADP was based on Cochran-Mantel Haenszel stratified analysis adjusting for Baseline stratification factor: Baseline third agent (PI, NNRTI, and INSTI).
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    741
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 Adjusted difference in proportion (ADP)
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 0.7
    Notes
    [3] - Non-inferiority of switching to DTG + 3TC compared to continuation of TBR (as per FDA snapshot algorithm) was to be concluded if the upper bound of a two-sided 95% confidence interval (CI) for the difference in virologic failure rates between the two treatment arms was smaller than 4%.

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

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    End point title
    		 Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Week 48
    End point description
    Percentage of participants with plasma HIV-1 RNA <50 c/mL (virologic success) was evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG +3TC once daily compared to continuation of TBR over 48 weeks. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [4]
    372 [5]
    Units: Percentage of participants
        number (not applicable)
    93.2
    93.0
    Notes
    [4] - ITT-E Population.
    [5] - ITT-E Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    ADP was based on Cochran-Mantel Haenszel stratified analysis adjusting for Baseline stratification factor: Baseline third agent (PI, NNRTI, and INSTI).
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    741
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    Parameter type
    		 Adjusted difference in proportion
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 3.9
    Notes
    [6] - Non-inferiority of switching to DTG + 3TC compared to continuation of TBR (as per FDA snapshot algorithm) was to be concluded when the lower bound of a 2-sided 95% confidence interval for the difference in success rates between the two treatment arms was greater than -8%.

    Secondary: Percentage of participants with virologic failure endpoint as per FDA snapshot category at Week 24

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    End point title
    		 Percentage of participants with virologic failure endpoint as per FDA snapshot category at Week 24
    End point description
    Percentage of participants with plasma HIV-1 RNA >=50 c/mL was evaluated using FDA snapshot algorithm at Week 24. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [7]
    372 [8]
    Units: Percentage of participants
        number (not applicable)
    0.3
    0.8
    Notes
    [7] - ITT-E Population.
    [8] - ITT-E Population.
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Week 24
    End point description
    Percentage of participants with plasma HIV-1 RNA <50 c/mL was evaluated using FDA snapshot algorithm at Week 24. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [9]
    372 [10]
    Units: Percentage of participants
    95
    96
    Notes
    [9] - ITT-E Population.
    [10] - ITT-E Population.
    No statistical analyses for this end point

    Secondary: Change from Baseline in CD4+ cell count at Weeks 24 and 48

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    End point title
    		 Change from Baseline in CD4+ cell count at Weeks 24 and 48
    End point description
    CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable. All 741 (369+372) participants were analyzed, however only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [11]
    372 [12]
    Units: Cells per cubic millimeter
    median (inter-quartile range (Q1-Q3))
        Week 24, n=351, 359
    21.0 (-68.0 to 115.0)
    6.0 (-87.0 to 99.0)
        Week 48, n=344, 345
    22.5 (-71.0 to 121.5)
    11.0 (-98.0 to 90.0)
    Notes
    [11] - ITT-E Population.
    [12] - ITT-E Population.
    No statistical analyses for this end point

    Secondary: Change from Baseline in CD4+/CD8+ cell count ratio at Weeks 24 and 48

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    End point title
    		 Change from Baseline in CD4+/CD8+ cell count ratio at Weeks 24 and 48
    End point description
    Blood samples were collected at specified time points to assess CD4+/CD8+ cell count ratio. It was assessed by flow cyclometry to evaluate the immunologic activity of switching to DTG+3TC once daily compared to continuation of TBR over 48 Weeks. Baseline (Day 1) values were the actual CD4+ cell count ratio values at pre-dose Day 1. Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable. All 741 (369+372) participants were analyzed, however only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [13]
    372 [14]
    Units: Ratio
    median (inter-quartile range (Q1-Q3))
        Baseline (Day 1), n=366, 371
    0.950 (0.710 to 1.250)
    0.960 (0.730 to 1.310)
        Week 24, n=346, 358
    0.010 (-0.070 to 0.110)
    0.040 (-0.060 to 0.120)
        Week 48, n=342, 343
    0.030 (-0.050 to 0.110)
    0.050 (-0.050 to 0.160)
    Notes
    [13] - ITT-E Population.
    [14] - ITT-E Population.
    No statistical analyses for this end point

    Secondary: Number of participants with disease progression at Weeks 24 and 48

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    End point title
    		 Number of participants with disease progression at Weeks 24 and 48
    End point description
    HIV-associated conditions were recorded during the study and was assessed according to the 2014 CDC Classification System for HIV Infection in Adults. Disease progression summarize participants who had HIV infection stage 3 associated conditions or death. Indicators of clinical disease progression were defined as: CDC Category Stage 1 at enrolment to Stage 3 event; CDC Category Stage 2 at enrolment to Stage 3 event; CDC Category Stage 3 at enrolment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrolment to Death. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable.
    End point type
    Secondary
    End point timeframe
    At Weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [15]
    372 [16]
    Units: Participants
        From CDC Stage 1 to CDC Stage 3 Event
    1
    0
        From CDC Stage 2 to CDC Stage 3 Event
    0
    0
        From CDC Stage 3 to new CDC Stage 3 Event
    0
    0
        From CDC Stage 1, 2 or 3 to Death
    1
    0
        No HIV-1 disease progression
    367
    372
    Notes
    [15] - ITT-E Population.
    [16] - ITT-E Population.
    No statistical analyses for this end point

    Secondary: Number of participants with any serious adverse events (SAEs) and common (>=2%) non-serious adverse events (non-SAEs)

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    End point title
    		 Number of participants with any serious adverse events (SAEs) and common (>=2%) non-serious adverse events (non-SAEs)
    End point description
    An AE is any untoward medical occurrence temporally associated with use of a study treatment, whether or not considered related to study treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Safety Population included participants who received at least 1 dose of study treatment and was based on treatment the participant actually received. One participant randomized to TBR but received TDF-based regimen and because safety profiles of TDF and TAF differ, this participant was removed from overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [17]
    371 [18]
    Units: Participants
        Any non-SAE (>=2%)
    222
    204
        Any SAE
    21
    16
    Notes
    [17] - Safety Population.
    [18] - Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with any SAEs and common (>=2%) non-SAEs

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    End point title
    		 Number of participants randomized to TBR arm receiving TDF-based regimen with any SAEs and common (>=2%) non-SAEs
    End point description
    An AE is any untoward medical occurrence temporally associated with the use of a study treatment, whether or not considered related to study treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Number of TDF-based regimen participants with any SAE and common (>=2%) non-SAEs are presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [19]
    Units: Participants
        Any non-SAE (>=2%)
    1
        Any SAE
    0
    Notes
    [19] - Safety Population.
    No statistical analyses for this end point

    Secondary: Number of Participants with AEs by their severity Grades

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    End point title
    		 Number of Participants with AEs by their severity Grades
    End point description
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [20]
    371 [21]
    Units: Participants
        Grade 1
    102
    94
        Grade 2
    170
    177
        Grade 3
    19
    15
        Grade 4
    3
    6
        Grade 5
    1
    0
    Notes
    [20] - Safety Population.
    [21] - Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with AEs by their severity Grades

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    End point title
    		 Number of participants randomized to TBR arm receiving TDF-based regimen with AEs by their severity Grades
    End point description
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the DAIDS toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of TDF-based regimen participants with adverse events by maximum grade have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [22]
    Units: Participants
        Grade 1
    0
        Grade 2
    1
        Grade 3
    0
        Grade 4
    0
        Grade 5
    0
    Notes
    [22] - Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants who discontinued the treatment due to AEs

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    End point title
    		 Number of participants who discontinued the treatment due to AEs
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Number of participants who discontinued the treatment due to adverse events have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [23]
    371 [24]
    Units: Participants
    13
    2
    Notes
    [23] - Safety Population.
    [24] - Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen who discontinued the treatment due to AEs

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    End point title
    		 Number of participants randomized to TBR arm receiving TDF-based regimen who discontinued the treatment due to AEs
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Number of participants who discontinued the treatment due to adverse events have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [25]
    Units: Participants
    0
    Notes
    [25] - Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with Maximum Post-Baseline emergent hematology toxicities

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    End point title
    		 Number of participants with Maximum Post-Baseline emergent hematology toxicities
    End point description
    Blood samples were collected up to Week 48 for the analysis of hematology parameters-platelet count, neutrophils, hemoglobin and leukocytes. Any abmormality in hematology parameters were evaluated according to the DAIDS toxicity scale from Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent hematology toxicities in any of the hematology parameters have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [26]
    371 [27]
    Units: Participants
        Hemoglobin, Grade 1
    3
    0
        Hemoglobin, Grade 2
    0
    0
        Hemoglobin, Grade 3
    0
    0
        Hemoglobin, Grade 4
    0
    0
        Leukocytes, Grade 1
    1
    1
        Leukocytes, Grade 2
    1
    0
        Leukocytes, Grade 3
    0
    0
        Leukocytes, Grade 4
    0
    0
        Neutrophils, Grade 1
    3
    4
        Neutrophils, Grade 2
    2
    4
        Neutrophils, Grade 3
    0
    0
        Neutrophils, Grade 4
    1
    0
        Platelets, Grade 1
    6
    5
        Platelets, Grade 2
    1
    1
        Platelets, Grade 3
    0
    0
        Platelets, Grade 4
    0
    0
    Notes
    [26] - Safety Population.
    [27] - Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent hematology toxicities

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    End point title
    		 Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent hematology toxicities
    End point description
    Blood samples were collected up to the Week 48 visit (participant withdrew from the study at Week 36) for the analysis of hematology parameters-platelet count, neutrophils, hemoglobin and leukocytes. Any abnormality in hematology parameters were evaluated according to the DAIDS toxicity scale from Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms. Only those TDF-based regimen participants with maximum post-Baseline emergent hematology toxicities in any of the hematology parameters have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [28]
    Units: Participants
        Hemoglobin, Grade 1
    0
        Hemoglobin, Grade 2
    0
        Hemoglobin, Grade 3
    0
        Hemoglobin, Grade 4
    0
        Leukocytes, Grade 1
    0
        Leukocytes, Grade 2
    0
        Leukocytes, Grade 3
    0
        Leukocytes, Grade 4
    0
        Neutrophils, Grade 1
    0
        Neutrophils, Grade 2
    0
        Neutrophils, Grade 3
    0
        Neutrophils, Grade 4
    0
        Platelets, Grade 1
    0
        Platelets, Grade 2
    0
        Platelets, Grade 3
    0
        Platelets, Grade 4
    0
    Notes
    [28] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with Maximum Post-Baseline emergent clinical chemistry toxicities

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    End point title
    		 Number of participants with Maximum Post-Baseline emergent clinical chemistry toxicities
    End point description
    Blood samples were collected for analysis of alanine aminotransferase(ALT), albumin, alkaline phosphate(ALP), aspartate aminotransferase(AST), bilirubin, carbon dioxide(CO2), cholesterol, creatinine kinase(CK), creatinine, direct bilirubin, glomerular filtration rate(GFR) from creatinine adjusted for body surface area(BSA), GFR from cystatin C adjusted using chronic kidney disease-epidemiology collaboration(CKD-EPI), hyper/hypocalcemia, hyper/hypo-glycemia, hyper/hypo-kalemia, hyper/hypo-natremia, low density lipoprotein(LDL) cholesterol, phosphate and triglycerides. Any abnormality was evaluated according to DAIDS toxicity scale From Grade1-4 as mild,moderates,evere and Potentially life-threatening. Higher the grade, more severe the symptoms. 1 participant randomized to TBR but received TDF and because safety profiles of TDF and TAF differ, this participant was removed from overall safety population and presented in separate arm "Randomized to TBR but received TDF-based regimen."
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [29]
    371 [30]
    Units: Participants
        ALT, Grade 1
    24
    18
        ALT, Grade 2
    6
    4
        ALT, Grade 3
    1
    1
        ALT, Grade 4
    0
    0
        Albumin, Grade 1
    1
    0
        Albumin, Grade 2
    0
    0
        Albumin, Grade 3
    0
    0
        Albumin, Grade 4
    0
    0
        ALP, Grade 1
    2
    0
        ALP, Grade 2
    0
    0
        ALP, Grade 3
    0
    0
        ALP, Grade 4
    0
    0
        AST, Grade 1
    21
    29
        AST, Grade 2
    7
    4
        AST, Grade 3
    1
    0
        AST, Grade 4
    1
    0
        Bilirubin, Grade 1
    17
    7
        Bilirubin, Grade 2
    5
    2
        Bilirubin, Grade 3
    1
    1
        Bilirubin, Grade 4
    0
    0
        CO2, Grade 1
    73
    70
        CO2, Grade 2
    1
    1
        CO2, Grade 3
    0
    0
        CO2, Grade 4
    0
    0
        Cholesterol, Grade 1
    27
    52
        Cholesterol, Grade 2
    12
    19
        Cholesterol, Grade 3
    1
    0
        Cholesterol, Grade 4
    0
    0
        CK, Grade 1
    28
    19
        CK, Grade 2
    4
    9
        CK, Grade 3
    9
    8
        CK, Grade 4
    6
    5
        Creatinine, Grade 1
    16
    7
        Creatinine, Grade 2
    3
    1
        Creatinine, Grade 3
    0
    0
        Creatinine, Grade 4
    0
    0
        Direct bilirubin, Grade 1
    0
    0
        Direct bilirubin, Grade 2
    0
    0
        Direct bilirubin, Grade 3
    8
    1
        Direct bilirubin, Grade 4
    0
    0
        GFR from creatinine adjusted using CKD EPI,Grade 1
    0
    0
        GFR from creatinine adjusted using CKD EPI,Grade 2
    135
    83
        GFR from creatinine adjusted using CKD EPI,Grade 3
    26
    13
        GFR from creatinine adjusted using CKD EPI,Grade 4
    0
    0
        GFR from cystatin C adjusted using CKD-EPI,Grade 1
    0
    0
        GFR from cystatin C adjusted using CKD-EPI,Grade 2
    52
    66
        GFR from cystatin C adjusted using CKD-EPI,Grade 3
    5
    4
        GFR from cystatin C adjusted using CKD-EPI,Grade 4
    1
    0
        Hypercalcemia, Grade 1
    7
    3
        Hypercalcemia, Grade 2
    0
    0
        Hypercalcemia, Grade 3
    0
    0
        Hypercalcemia, Grade 4
    0
    0
        Hyperglycemia, Grade 1
    56
    64
        Hyperglycemia, Grade 2
    21
    19
        Hyperglycemia, Grade 3
    2
    2
        Hyperglycemia, Grade 4
    0
    0
        Hyperkalemia, Grade 1
    0
    2
        Hyperkalemia, Grade 2
    2
    0
        Hyperkalemia, Grade 3
    0
    0
        Hyperkalemia, Grade 4
    0
    0
        Hypernatremia, Grade 1
    1
    1
        Hypernatremia, Grade 2
    0
    0
        Hypernatremia, Grade 3
    0
    0
        Hypernatremia, Grade 4
    0
    0
        Hypocalcemia, Grade 1
    8
    1
        Hypocalcemia, Grade 2
    0
    1
        Hypocalcemia, Grade 3
    0
    0
        Hypocalcemia, Grade 4
    0
    0
        Hypoglycemia, Grade 1
    5
    6
        Hypoglycemia, Grade 2
    3
    2
        Hypoglycemia, Grade 3
    0
    0
        Hypoglycemia, Grade 4
    0
    0
        Hypokalemia, Grade 1
    7
    1
        Hypokalemia, Grade 2
    1
    0
        Hypokalemia, Grade 3
    0
    0
        Hypokalemia, Grade 4
    0
    0
        Hyponatremia, Grade 1
    8
    13
        Hyponatremia, Grade 2
    0
    2
        Hyponatremia, Grade 3
    0
    0
        Hyponatremia, Grade 4
    0
    0
        LDL cholesterol, Grade 1
    28
    35
        LDL cholesterol, Grade 2
    13
    15
        LDL cholesterol, Grade 3
    6
    3
        LDL cholesterol, Grade 4
    0
    0
        Phosphate, Grade 1
    38
    47
        Phosphate, Grade 2
    2
    7
        Phosphate, Grade 3
    0
    0
        Phosphate, Grade 4
    0
    0
        Triglycerides, Grade 1
    34
    48
        Triglycerides, Grade 2
    4
    11
        Triglycerides, Grade 3
    4
    4
        Triglycerides, Grade 4
    4
    0
    Notes
    [29] - Safety Population.
    [30] - Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent clinical chemistry toxicities

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    End point title
    		 Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent clinical chemistry toxicities
    End point description
    Blood samples were collected up to Week 48 visit (participant withdrew from the study at Week 36) for analysis of clinical chemistry parameters: ALT, albumin, ALP, AST, bilirubin, CO2, cholesterol, CK, creatinine, direct bilirubin, GFR from creatinine adjusted for BSA, GFR from cystatin C adjusted using CKD-EPI, hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, LDL cholesterol, phosphate and triglycerides. Any abnormality in clinical chemistry parameters were evaluated according to DAIDS toxicity scale From Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). Higher the grade, more severe the symptoms. One participant randomized to TBR but received TDF-based regimen and because safety profiles of TDF and TAF differ, this participant was removed from overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [31]
    Units: Participants
        ALT, Grade 1
    0
        ALT, Grade 2
    0
        ALT, Grade 3
    0
        ALT, Grade 4
    0
        Albumin, Grade 1
    0
        Albumin, Grade 2
    0
        Albumin, Grade 3
    0
        Albumin, Grade 4
    0
        ALP, Grade 1
    0
        ALP, Grade 2
    0
        ALP, Grade 3
    0
        ALP, Grade 4
    0
        AST, Grade 1
    0
        AST, Grade 2
    0
        AST, Grade 3
    0
        AST, Grade 4
    0
        Bilirubin, Grade 1
    0
        Bilirubin, Grade 2
    0
        Bilirubin, Grade 3
    0
        Bilirubin, Grade 4
    0
        CO2, Grade 1
    0
        CO2, Grade 2
    0
        CO2, Grade 3
    0
        CO2, Grade 4
    0
        Cholesterol, Grade 1
    0
        Cholesterol, Grade 2
    0
        Cholesterol, Grade 3
    0
        Cholesterol, Grade 4
    0
        CK, Grade 1
    0
        CK, Grade 2
    0
        CK, Grade 3
    0
        CK, Grade 4
    0
        Creatinine, Grade 1
    0
        Creatinine, Grade 2
    0
        Creatinine, Grade 3
    0
        Creatinine, Grade 4
    0
        Direct bilirubin, Grade 1
    0
        Direct bilirubin, Grade 2
    0
        Direct bilirubin, Grade 3
    0
        Direct bilirubin, Grade 4
    0
        GFR from creatinine adjusted using CKD EPI,Grade 1
    0
        GFR from creatinine adjusted using CKD EPI,Grade 2
    0
        GFR from creatinine adjusted using CKD EPI,Grade 3
    0
        GFR from creatinine adjusted using CKD EPI,Grade 4
    0
        GFR from cystatin C adjusted using CKD-EPI,Grade 1
    0
        GFR from cystatin C adjusted using CKD-EPI,Grade 2
    0
        GFR from cystatin C adjusted using CKD-EPI,Grade 3
    0
        GFR from cystatin C adjusted using CKD-EPI,Grade 4
    0
        Hypercalcemia, Grade 1
    0
        Hypercalcemia, Grade 2
    0
        Hypercalcemia, Grade 3
    0
        Hypercalcemia, Grade 4
    0
        Hyperglycemia, Grade 1
    0
        Hyperglycemia, Grade 2
    0
        Hyperglycemia, Grade 3
    0
        Hyperglycemia, Grade 4
    0
        Hyperkalemia, Grade 1
    0
        Hyperkalemia, Grade 2
    0
        Hyperkalemia, Grade 3
    0
        Hyperkalemia, Grade 4
    0
        Hypernatremia, Grade 1
    0
        Hypernatremia, Grade 2
    0
        Hypernatremia, Grade 3
    0
        Hypernatremia, Grade 4
    0
        Hypocalcemia, Grade 1
    0
        Hypocalcemia, Grade 2
    0
        Hypocalcemia, Grade 3
    0
        Hypocalcemia, Grade 4
    0
        Hypoglycemia, Grade 1
    0
        Hypoglycemia, Grade 2
    0
        Hypoglycemia, Grade 3
    0
        Hypoglycemia, Grade 4
    0
        Hypokalemia, Grade 1
    0
        Hypokalemia, Grade 2
    0
        Hypokalemia, Grade 3
    0
        Hypokalemia, Grade 4
    0
        Hyponatremia, Grade 1
    0
        Hyponatremia, Grade 2
    0
        Hyponatremia, Grade 3
    0
        Hyponatremia, Grade 4
    0
        LDL cholesterol, Grade 1
    0
        LDL cholesterol, Grade 2
    0
        LDL cholesterol, Grade 3
    0
        LDL cholesterol, Grade 4
    0
        Phosphate, Grade 1
    0
        Phosphate, Grade 2
    0
        Phosphate, Grade 3
    0
        Phosphate, Grade 4
    0
        Triglycerides, Grade 1
    1
        Triglycerides, Grade 2
    0
        Triglycerides, Grade 3
    0
        Triglycerides, Grade 4
    0
    Notes
    [31] - Safety Population.
    No statistical analyses for this end point

    Secondary: Change from Baseline in renal biomarkers- Urine albumin/creatinine (UA/C) ratio and Urine protein/creatinine (UP/C) ratio at Weeks 24 and 48

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    End point title
    		 Change from Baseline in renal biomarkers- Urine albumin/creatinine (UA/C) ratio and Urine protein/creatinine (UP/C) ratio at Weeks 24 and 48
    End point description
    Baseline is defined as Day 1. Change from Baseline in UA/C was calculated as UA/C ratio at post-Baseline visit minus UA/C ratio calculated at Baseline. Estimated geometric mean adjusted ratio (each visit over Baseline) and 95% CI have been presented. Change from Baseline in UP/C and UA/C was calculated as UP/C and UA/C ratio at post-Baseline visit minus UP/C and UA/C ratio calculated at Baseline, respectively. Estimated geometric mean adjusted ratio (each visit over Baseline) and 95% CI have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." All 741 (369+372) participants were analyzed, however only those participants with data available at specified data points were analyzed (represented by n= X in category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [32]
    371 [33]
    Units: Ratio
    geometric mean (confidence interval 95%)
        UA/C, Week 24, n=235, 230
    1.080 (1.007 to 1.158)
    1.022 (0.956 to 1.091)
        UA/C, Week 48, n=230, 224
    1.125 (1.036 to 1.222)
    1.059 (0.963 to 1.165)
        UP/C, Week 24, n=267, 261
    0.955 (0.917 to 0.995)
    0.976 (0.937 to 1.016)
        UP/C, Week 48, n=261, 257
    0.971 (0.926 to 1.018)
    1.016 (0.964 to 1.070)
    Notes
    [32] - Safety Population.
    [33] - Safety Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UA/C at Week 24 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.257
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Treatment ratio
    Point estimate
    1.057
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.164
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UA/C at Week 48 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.35
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Treatment ratio
    Point estimate
    1.062
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.936
         upper limit
    		 1.205
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UP/C at Week 24 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.473
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Treatment ratio
    Point estimate
    0.979
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.924
         upper limit
    		 1.037
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UP/C at Week 48 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.212
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Treatment ratio
    Point estimate
    0.956
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.891
         upper limit
    		 1.026

    Secondary: Change from Baseline in renal biomarkers- UA/C ratio and UP/C ratio at Weeks 24 and 48 in participants randomized to TBR receiving TDF-based regimen

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    End point title
    		 Change from Baseline in renal biomarkers- UA/C ratio and UP/C ratio at Weeks 24 and 48 in participants randomized to TBR receiving TDF-based regimen
    End point description
    Urine samples were collected at Baseline, Week 24 and Week 48 to assess renal biomarkers - urine albumin/creatinine ratio and urine protein/creatinine ratio. Baseline was defined as the latest pre-dose assessment value (Day 1) with a non-missing value. Change from Baseline in UP/C and UA/C was calculated as UP/C and UA/C ratio at post-Baseline visit minus UP/C and UA/C ratio calculated at Baseline, respectively. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at weeks 24 and 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [34]
    Units: Ratio
    number (not applicable)
        UA/C, Week 24, n=1
    0
        UA/C, Week 48, n=0
    99999
        UP/C, Week 24, n=1
    0.3
        UP/C, Week 48, n=0
    99999
    Notes
    [34] - Safety Population. 99999 indicates no participant has been analyzed
    No statistical analyses for this end point

    Secondary: Ratio to Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine

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    End point title
    		 Ratio to Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine
    End point description
    Urine biomarker samples were collected at Baseline and Week 48. Geometric mean ratio (visit divided by Baseline) and 95% CI of geometric mean ratio has been presented. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine beta-2-microglobulin/urine creatinine was calculated as urine beta-2-microglobulin/urine creatinine ratio at post-Baseline visit minus urine beta-2-microglobulin/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." All 741 (369+372) participants were analyzed, however only those participants with data available at specified data points were analyzed (represented by n=X in category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [35]
    371 [36]
    Units: Ratio
    geometric mean (confidence interval 95%)
        Week 24, n=136, 141
    0.991 (0.899 to 1.093)
    1.034 (0.931 to 1.149)
        Week 48, n=126, 141
    0.973 (0.870 to 1.088)
    0.922 (0.832 to 1.022)
    Notes
    [35] - Safety Population.
    [36] - Safety Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine beta-2 microglobulin/urine creatinine at Week 24 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.56
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Treatment ratio
    Point estimate
    0.958
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.106
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine beta-2 microglobulin/urine creatinine at Week 48 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.489
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Treatment ratio
    Point estimate
    1.055
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.906
         upper limit
    		 1.229

    Secondary: Change from Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine ratio in participants randomized to TBR arm receiving TDF-based regimen

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    End point title
    		 Change from Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine ratio in participants randomized to TBR arm receiving TDF-based regimen
    End point description
    Urine biomarker samples were collected to assess urine beta-2 microglobulin/urine creatinine. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine beta-2-microglobulin/urine creatinine was calculated as urine beta-2-microglobulin/urine creatinine ratio at post-Baseline visit minus urine beta-2-microglobulin/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at weeks 24 and 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [37]
    Units: Ratio
        Week 24
    99999
        Week 48
    99999
    Notes
    [37] - Safety Population. 99999 indicates data was not collected for this outcome for this arm.
    No statistical analyses for this end point

    Secondary: Ratio to Baseline in renal biomarkers- Urine phosphate

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    End point title
    		 Ratio to Baseline in renal biomarkers- Urine phosphate
    End point description
    Urine biomarker samples were collected at Baseline and at Weeks 24 and 48 to assess urine phosphate. Geometric mean ratio (visit divided by Baseline) and 95% CI of geometric mean ratio has been presented. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine phosphate was calculated as urine phosphate at post-Baseline visit minus urine phosphate calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." All 741 (369+372) participants were analyzed, however only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [38]
    371 [39]
    Units: Ratio
    geometric mean (confidence interval 95%)
        Week 24, n=348, 352
    0.955 (0.888 to 1.028)
    0.940 (0.871 to 1.014)
        Week 48, n=342, 340
    0.969 (0.892 to 1.052)
    0.970 (0.900 to 1.044)
    Notes
    [38] - Safety Population.
    [39] - Safety Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine phosphate at Week 24 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.758
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Treatment ratio
    Point estimate
    1.017
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.915
         upper limit
    		 1.13
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine phosphate at Week 48 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.985
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Treatment ratio
    Point estimate
    0.999
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.894
         upper limit
    		 1.116

    Secondary: Change from Baseline in renal biomarkers- Urine phosphate in participants randomized to TBR arm receiving TDF-based regimen

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    End point title
    		 Change from Baseline in renal biomarkers- Urine phosphate in participants randomized to TBR arm receiving TDF-based regimen
    End point description
    Urine biomarker samples were collected to assess urine phosphate. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine phosphate was calculated as urine phosphate at post-Baseline visit minus urine phosphate calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at weeks 24 and 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [40]
    Units: Ratio
    number (not applicable)
        Week 24, n=1
    2.9
        Week 48, n=0
    99999
    Notes
    [40] - Safety Population. 99999 indicates no participant has been analyzed
    No statistical analyses for this end point

    Secondary: Ratio to Baseline in renal biomarkers- Urine retinol binding protein 4/urine creatinine

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    End point title
    		 Ratio to Baseline in renal biomarkers- Urine retinol binding protein 4/urine creatinine
    End point description
    Urine biomarker samples were collected at Baseline and Week 48. Geometric mean ratio (visit divided by Baseline) and 95% CI of geometric mean ratio has been presented. Baseline is defined as Day 1. Change from Baseline in Urine retinol binding protein 4/urine creatinine ratio was calculated as Urine retinol binding protein 4/urine creatinine ratio at post-Baseline visit minus Urine retinol binding protein 4/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." All 741 (369+372) participants were analyzed, however only those participants with data available at specified data points were analyzed (represented by n=X in category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [41]
    371 [42]
    Units: Ratio
    geometric mean (confidence interval 95%)
        Week 24, n=344, 343
    0.860 (0.790 to 0.936)
    0.920 (0.847 to 0.999)
        Week 48, n=340, 335
    1.063 (0.992 to 1.139)
    1.068 (0.996 to 1.144)
    Notes
    [41] - Safety Population.
    [42] - Safety Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine retinol binding protein 4/urine creatinine at Week 24 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.264
    Method
    		 Mixed Model Reported Measures
    Parameter type
    		 Treatment ratio
    Point estimate
    0.935
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.052
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine retinol binding protein 4/urine creatinine at Week 48 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.932
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Treatment ratio
    Point estimate
    0.996
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.903
         upper limit
    		 1.098

    Secondary: Change from Baseline in renal biomarkers- Urine retinol binding protein 4/urine creatinine in participants randomized to TBR arm receiving TDF-based regimen

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    End point title
    		 Change from Baseline in renal biomarkers- Urine retinol binding protein 4/urine creatinine in participants randomized to TBR arm receiving TDF-based regimen
    End point description
    Urine samples were collected to assess urine retinol binding protein 4/urine creatinine. Baseline was defined as Day 1. Change from Baseline in urine retinol binding protein 4/urine creatinine was calculated as urine retinol binding protein 4/urine creatinine ratio at post-Baseline visit minus urine retinol binding protein 4/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because safety profiles of TDF and TAF differ, this participant was removed from overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine retinol binding protein 4/urine creatinine at Week 48 has been presented. Participants with data available at specified data points were analyzed (represented by n= X in category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at weeks 24 and 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [43]
    Units: Ratio
    number (not applicable)
        Week 24, n=1
    1.04
        Week 48, n=0
    99999
    Notes
    [43] - Safety Population. 99999 indicates no participant has been analyzed.
    No statistical analyses for this end point

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

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    End point title
    		 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 plasma cholesterol, plasma LDL cholesterol, plasma high density lipoprotein (HDL) cholesterol and plasma triglycerides. Baseline value was the value from the latest pre-dose assessment (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." All 741 (369+372) participants were analyzed, however only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [44]
    371 [45]
    Units: Millimoles per liter
    median (inter-quartile range (Q1-Q3))
        Plasma cholesterol, Week 24, n=282, 264
    -0.325 (-0.750 to 0.150)
    0.000 (-0.400 to 0.400)
        Plasma cholesterol, Week 48, n=275, 263
    -0.200 (-0.750 to 0.150)
    0.100 (-0.350 to 0.500)
        Plasma LDL Cholesterol, Week 24, n=282, 264
    -0.210 (-0.570 to 0.130)
    -0.060 (-0.340 to 0.410)
        Plasma LDL Cholesterol, Week 48, n=275, 263
    -0.170 (-0.560 to 0.210)
    0.070 (-0.320 to 0.430)
        Plasma Triglycerides, Week 24, n=282, 264
    -0.100 (-0.460 to 0.160)
    0.060 (-0.200 to 0.350)
        Plasma Triglycerides, Week 48, n=275, 263
    -0.100 (-0.440 to 0.160)
    0.100 (-0.280 to 0.380)
        Plasma HDL Cholesterol, Week 24, n=282, 264
    -0.050 (-0.150 to 0.100)
    0.050 (-0.150 to 0.150)
        Plasma HDL Cholesterol, Week 48, n=275, 263
    0.000 (-0.200 to 0.150)
    0.050 (-0.150 to 0.150)
    Notes
    [44] - Safety Population.
    [45] - Safety Population.
    No statistical analyses for this end point

    Secondary: Change from Baseline in fasting lipids at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

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    End point title
    		 Change from Baseline in fasting lipids at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen
    End point description
    Blood samples were collected up to the Week 48 visit (participant withdrew from the study at Week 36) to assess fasting lipids which included plasma cholesterol, plasma LDL cholesterol, plasma HDL cholesterol and plasma triglycerides. Baseline value was the value from the latest pre-dose assessment (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline values for fasting lipids in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at weeks 24 and 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [46]
    Units: Millimoles per liter
    number (not applicable)
        Plasma cholesterol, Week 24, n=1
    0
        Plasma cholesterol, Week 48, n=0
    99999
        Plasma LDL Cholesterol, Week 24, n=1
    -0.67
        Plasma LDL Cholesterol, Week 48, n=0
    99999
        Plasma Triglycerides, Week 24, n=1
    1.36
        Plasma Triglycerides, Week 48, n=0
    99999
        Plasma HDL Cholesterol, Week 24, n=1
    0.05
        Plasma HDL Cholesterol, Week 48, n=0
    99999
    Notes
    [46] - Safety Population. 9999 indicates no participant has been analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants with genotypic resistance

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    End point title
    		 Number of participants with genotypic resistance
    End point description
    Plasma samples were collected for drug resistance testing. Number of participants, who met confirmed virologic withdrawal (CVW) criteria (one plasma HIV-1 RNA >=200 c/mL after Day 1 with immediate prior HIV RNA >=50 c/mL), with emergent genotypic resistance to INSTI, nucleoside reverse transcriptase inhibitor (NRTI), NNRTI and PI was summarized. CVW Population comprises all participants in the ITT-E Population who had met the derived CVW criteria. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    0 [47]
    1 [48]
    Units: Participants
        INSTI
    0
        NRTI
    0
        NNRTI
    0
        PI
    0
    Notes
    [47] - CVW Population.
    [48] - CVW Population.
    No statistical analyses for this end point

    Secondary: Number of participants with phenotypic resistance

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    End point title
    		 Number of participants with phenotypic resistance
    End point description
    Number of participants, who meet CVW criteria (one plasma HIV-1 RNA >=200 c/mL after Day 1 with immediate prior HIV RNA >=50 c/mL), with emergent phenotypic resistance to INSTI and/or NRTI were summarized. Assessment of antiviral activity of anti-retroviral therapy (ART) using phenotypic test results was interpreted through a proprietary algorithm (from Monogram Biosciences), which provided the overall susceptibility of the drug. Partially sensitive and resistant calls were considered resistant in this analysis. The phenotypic resistance was calculated using binary scoring system, where 0 was considered as sensitive and 1 as resistance. Phenotypic Resistance data for the following INSTI, NNRTI, NRTI and PI drugs in participants Meeting CVW Criteria has been presented. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    0 [49]
    1 [50]
    Units: Participants
        INSTI, DTG, Sensitive
    1
        INSTI, DTG, Resistant
    0
        INSTI, Bictegravir (BIC), Sensitive
    1
        INSTI, BIC, Resistant
    0
        INSTI, Elvitegravir (EVG), Sensitive
    1
        INSTI, EVG, Resistant
    0
        INSTI, Raltegravir (RAL), Sensitive
    1
        INSTI, RAL, Resistant
    0
        NNRTI, Delavirdine (DLV), Sensitive
    1
        NNRTI, DLV, Resistant
    0
        NNRTI, Efavirenz (EFV), Sensitive
    1
        NNRTI, EFV, Resistant
    0
        NNRTI, Etravirine (ETR), Sensitive
    1
        NNRTI, ETR, Resistant
    0
        NNRTI, Nevirapine (NVP), Sensitive
    1
        NNRTI, NVP, Resistant
    0
        NNRTI, Rilpivirine (RPV), Sensitive
    1
        NNRTI, RPV, Resistant
    0
        NRTI, 3TC, Sensitive
    1
        NRTI, 3TC, Resistant
    0
        NRTI, Abacavir (ABC), Sensitive
    1
        NRTI, ABC, Resistant
    0
        NRTI, Zidovudine (AZT), Sensitive
    1
        NRTI, AZT, Resistant
    0
        NRTI, Stavudine (D4T), Sensitive
    1
        NRTI, D4T, Resistant
    0
        NRTI, Didanosine (DDI), Sensitive
    1
        NRTI, DDI, Resistant
    0
        NRTI, Emtricitabine (FTC), Sensitive
    1
        NRTI, FTC, Resistant
    0
        NRTI, Tenofovir (TDF), Sensitive
    1
        NRTI, TDF, Resistant
    0
        PI, Atazanavir (ATV), Sensitive
    1
        PI, ATV, Resistant
    0
        PI, Darunavir (DRV), Sensitive
    1
        PI, DRV, Resistant
    0
        PI, Fosamprenavir (FPV), Sensitive
    1
        PI, FPV, Resistant
    0
        PI, Indinavir (IDV), Sensitive
    1
        PI, IDV, Resistant
    0
        PI, Lopinavir (LPV), Sensitive
    1
        PI, LPV, Resistant
    0
        PI, Nelfinavir (NFV), Sensitive
    1
        PI, NFV, Resistant
    0
        PI, Ritonavir (RTV), Sensitive
    1
        PI, RTV, Resistant
    0
        PI, Saquinavir (SQV), Sensitive
    1
        PI, SQV, Resistant
    0
        PI, Tipranavir (TPV), Sensitive
    1
        PI, TPV, Resistant
    0
    Notes
    [49] - CVW Population.
    [50] - CVW Population.
    No statistical analyses for this end point

    Secondary: Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum procollagen 1 N-Terminal propeptide (P1NP) and serum type 1 collagen C-telopeptides (CTX-1)

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    End point title
    		 Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum procollagen 1 N-Terminal propeptide (P1NP) and serum type 1 collagen C-telopeptides (CTX-1)
    End point description
    Baseline is defined as Day 1. Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for treatment, visit, Baseline third agent class, CD4+ cell count(continuous), age(continuous), sex, race, body mass index (BMI) (continuous), smoking status, vitamin D use, Baseline biomarker (continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor.One participant randomized to TBR but received TDF and because safety profiles of TDF and TAF differ, this participant was removed from overall safety population and presented in separate arm "Randomized to TBR but received TDF-based regimen." All 741 (369+372) participants were analyzed, however participants with data available at specified data points were analyzed (n= X in category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [51]
    371 [52]
    Units: Micrograms per liter
    arithmetic mean (standard error)
        Bone-ALP, Week 24, n=350, 354
    -0.77 ( 0.112 )
    -1.05 ( 0.089 )
        Bone-ALP, Week 48, n=343, 342
    -0.03 ( 0.145 )
    -0.34 ( 0.117 )
        Osteocalcin, Week 24, n=350 ,353
    -1.08 ( 0.248 )
    0.26 ( 0.229 )
        Osteocalcin, Week 48, n=343, 342
    -1.15 ( 0.260 )
    0.69 ( 0.279 )
        P1NP, Week24, n=349 ,356
    7.0 ( 0.87 )
    5.0 ( 0.72 )
        P1NP, Week48, n=342, 343
    9.3 ( 1.06 )
    6.4 ( 1.00 )
        CTX-1, Week 24,n=350,356
    0.0350 ( 0.01057 )
    -0.0031 ( 0.00833 )
        CTX-1, Week 48, n=343, 343
    0.0602 ( 0.01024 )
    0.0310 ( 0.00889 )
    Notes
    [51] - Safety Population.
    [52] - Safety Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Bone-ALP at Week 24 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.047
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.57
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Bone-ALP at Week 48 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.094
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.05
         upper limit
    		 0.68
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Osteocalcin at Week 24 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.01
         upper limit
    		 -0.68
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Osteocalcin at Week 48 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.59
         upper limit
    		 -1.09
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for P1NP at Week 24 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.066
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 4.3
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for P1NP at Week 48 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.046
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 5.8
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for CTX-1 at Week 24 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.005
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.0381
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.0117
         upper limit
    		 0.0646
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for CTX-1 at Week 48 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.032
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.0292
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.0025
         upper limit
    		 0.0559

    Secondary: Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum P1NP and serum CTX-1 in participants randomized to TBR arm receiving TDF-based regimen

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    End point title
    		 Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum P1NP and serum CTX-1 in participants randomized to TBR arm receiving TDF-based regimen
    End point description
    Serum samples were collected for analysis of bone biomarkers. Baseline was latest pre-dose assessment (Day 1) with a non-missing value. Change from Baseline is post-dose visit value minus Baseline value. Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum P1NP and serum CTX-1 in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [53]
    Units: Micrograms per liter
    number (not applicable)
        Bone-ALP, Week 24, n=1
    0.3
        Bone-ALP, Week 48, n=0
    99999
        Osteocalcin, Week 24, n=1
    13.4
        Osteocalcin, Week 48, n=0
    99999
        P1NP, Week24, n=1
    11
        P1NP, Week48, n=0
    99999
        CTX-1, Week 24,n=1
    0.045
        CTX-1, Week 48, n=0
    99999
    Notes
    [53] - Safety Population. 99999 indicates no participant has been analyzed
    No statistical analyses for this end point

    Secondary: Change from Baseline in bone biomarker: serum 25-hydroxyvitamin D

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    End point title
    		 Change from Baseline in bone biomarker: serum 25-hydroxyvitamin D
    End point description
    Baseline was defined as Day 1. Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for treatment, visit, Baseline third agent class, CD4+ cell count(continuous), age(continuous), sex, race, BMI(continuous), smoking status, vitamin D use, Baseline biomarker(continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor.One participant randomized to TBR but received TDF and because safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." All 741 (369+372) participants were analyzed, however participants with data available at specified data points were analyzed(n= X in category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [54]
    371 [55]
    Units: Nanomoles per liter
    arithmetic mean (standard error)
        Week 24, n=351, 355
    0.0 ( 1.10 )
    2.1 ( 1.15 )
        Week 48, n=344, 343
    -5.8 ( 1.21 )
    -3.5 ( 1.13 )
    Notes
    [54] - Safety Population.
    [55] - Safety Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum 25 hydroxyvitamin D at Week 24 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.173
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.3
         upper limit
    		 1
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum 25 hydroxyvitamin D at Week 48 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.168
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.5
         upper limit
    		 1

    Secondary: Change from Baseline in bone biomarker: serum 25-hydroxyvitamin D in participants randomized to TBR arm receiving TDF-based regimen

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    End point title
    		 Change from Baseline in bone biomarker: serum 25-hydroxyvitamin D in participants randomized to TBR arm receiving TDF-based regimen
    End point description
    Serum samples were collected for the analysis of 25-hydroxyvitamin D. Baseline value was the value from latest pre-dose assessment (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline values for serum 25-hydroxyvitamin D in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [56]
    Units: Nanomoles per liter
        Week 24, n=1
    2
        Week 48, n=0
    99999
    Notes
    [56] - Safety Population. 99999 indicates no participant has been analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in renal biomarker- serum cystatin C

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    End point title
    		 Change from Baseline in renal biomarker- serum cystatin C
    End point description
    Baseline was defined as Day1. Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for following:treatment, visit, Baseline third agent class, CD4+ cell count(continuous), age(continuous), sex, race, BMI(continuous), presence of diabetes mellitus, hypertension, Baseline biomarker(continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor.One participant randomized to TBR but received TDF and because safety profiles of TDF and TAF differ, this participant was removed from overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." All 741 (369+372) participants were analyzed, however participants with data available at specified data points were analyzed(n= X in category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [57]
    371 [58]
    Units: Milligrams per liter
    arithmetic mean (standard error)
        Week 24, n=351, 357
    -0.03 ( 0.005 )
    -0.02 ( 0.004 )
        Week 48, n=344, 343
    0.00 ( 0.006 )
    0.01 ( 0.005 )
    Notes
    [57] - Safety Population.
    [58] - Safety Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum cystatin C at Week 24 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.027
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 0
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum cystatin C at Week 48 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.061
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 0

    Secondary: Change from Baseline in renal biomarker- serum cystatin C in participants randomized to TBR arm receiving TDF-based regimen

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    End point title
    		 Change from Baseline in renal biomarker- serum cystatin C in participants randomized to TBR arm receiving TDF-based regimen
    End point description
    Serum samples were collected at Baseline, Week 24 and Week 48 to assess renal inflammation biomarker - cystatin C. Baseline was defined as the latest pre-dose assessment value (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline values for serum cystatin -C biomarker in TDF based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [59]
    Units: Milligrams per liter
        Week 24, n=1
    0
        Week 48, n=0
    99999
    Notes
    [59] - Safety Population. 99999 indicates no participant has been analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in renal biomarker- serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI at Weeks 24 and 48

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    End point title
    		 Change from Baseline in renal biomarker- serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI at Weeks 24 and 48
    End point description
    Baseline was defined as Day 1. Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for treatment, visit, Baseline third agent class, CD4+ cell count(continuous), age(continuous), sex, race, BMI(continuous), presence of diabetes mellitus, hypertension, Baseline biomarker (continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor. One participant randomized to TBR but received TDF and because safety profiles of TDF and TAF differ, this participant was removed from overall safety population and presented in separate arm "Randomized to TBR but received TDF-based regimen.” All 741 (369+372) participants were analyzed, however participants with data available at specified data points were analyzed (n= X in category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [60]
    371 [61]
    Units: Milliliters/minute/1.73*meter square
    arithmetic mean (standard error)
        GFR from cystatin C CKD-EPI, Week 24, n=351, 357
    3.2 ( 0.52 )
    1.5 ( 0.46 )
        GFR from cystatin C CKD-EPI, Week 48, n=344, 343
    0.1 ( 0.61 )
    -1.6 ( 0.59 )
        GFR from creatinine CKD-EPI, Week 24, n=351, 359
    -8.8 ( 0.48 )
    -3.8 ( 0.47 )
        GFR from creatinine CKD-EPI, Week 48, n=344, 345
    -7.7 ( 0.48 )
    -2.9 ( 0.48 )
    Notes
    [60] - Safety Population.
    [61] - Safety Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from cystatin C adjusted using CKD-EPI at Week 24 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.012
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 3.1
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from cystatin C adjusted using CKD-EPI at Week 48 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.059
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 3.3
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from creatinine adjusted using CKD-EPI at Week 24 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.3
         upper limit
    		 -3.7
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from creatinine adjusted using CKD-EPI at Week 48 has been presented
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -4.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.1
         upper limit
    		 -3.4

    Secondary: Change from Baseline in renal biomarker- serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

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    End point title
    		 Change from Baseline in renal biomarker- serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen
    End point description
    Serum samples were collected at Baseline, Week 24 and Week 48 to assess renal inflammation biomarkers - serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI. Baseline was defined as the latest pre-dose assessment value (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline in serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen.” Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [62]
    Units: Milliliters/minute/1.73*meter square
        GFR from cystatin C CKD-EPI, Week 24, n=1
    0
        GFR from cystatin C CKD-EPI, Week 48, n=0
    99999
        GFR from creatinine CKD-EPI, Week 24, n=1
    4
        GFR from creatinine CKD-EPI, Week 48, n=0
    99999
    Notes
    [62] - Safety Population. 99999 indicates no participant has been analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in renal biomarker- serum creatinine

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    End point title
    		 Change from Baseline in renal biomarker- serum creatinine
    End point description
    Baseline is defined as Day 1. Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from repeated measures model adjusting for treatment, visit, Baseline third agent class, CD4+ cell count(continuous), age(continuous), sex, race, BMI(continuous), presence of diabetes mellitus, hypertension, Baseline biomarker(continuous), treatment by visit interaction,and Baseline value by visit interaction, with visit as repeated factor. One participant randomized to TBR but received TDF and because safety profiles of TDF and TAF differ, this participant was removed from overall safety population and presented in separate arm "Randomized to TBR but received TDF-based regimen.” All 741(369+372) participants were analyzed, however participants with data available at specified data points were analyzed(n=X in category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    369 [63]
    371 [64]
    Units: Micromoles per liter
    arithmetic mean (standard error)
        Week 24, n=351, 359
    7.47 ( 0.466 )
    3.11 ( 0.495 )
        Week 48, n=344, 345
    6.67 ( 0.493 )
    2.18 ( 0.450 )
    Notes
    [63] - Safety Population.
    [64] - Safety Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Mean difference (DTG+3TC - TBR) and its 95% CI for serum creatinine at Week 24 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    4.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.03
         upper limit
    		 5.7
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Mean difference (DTG+3TC - TBR) and its 95% CI for serum creatinine at Week 48 has been presented.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    740
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    4.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.18
         upper limit
    		 5.81

    Secondary: Change from Baseline in renal biomarker- serum creatinine in participants randomized to TBR arm receiving TDF-based regimen

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    End point title
    		 Change from Baseline in renal biomarker- serum creatinine in participants randomized to TBR arm receiving TDF-based regimen
    End point description
    Serum samples were collected at Baseline, Week 24 and Week 48 to assess renal inflammation biomarker - serum creatinine. Baseline was defined as the latest pre-dose assessment value (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline in serum creatinine in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen.” Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 Randomized to TBR but received TDF-based regimen
    Number of subjects analysed
    1 [65]
    Units: Micromoles per liter
    number (not applicable)
        Week 24, n=1
    -8
        Week 48, n=0
    99999
    Notes
    [65] - Safety Population. 99999 indicates no participant has been analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) utility score at Week 24 and 48

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    End point title
    		 Change from Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) utility score at Week 24 and 48
    End point description
    EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. Five-item measure has 1 question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. Health state is defined by combining levels of answers from each of 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health. One participant randomized to TBR but received TDF and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable. Only those participants with data available at specified time points has been analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    364 [66]
    370 [67]
    Units: Scores on a scale
    arithmetic mean (standard error)
        Week 24
    0.0029 ( 0.00383 )
    0.0046 ( 0.00352 )
        Week 48
    0.0037 ( 0.00407 )
    0.0023 ( 0.00373 )
    Notes
    [66] - ITT-E Population.
    [67] - ITT-E Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 24. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Utility (continuous), Treatment by Visit interaction, and Baseline EQ-5D Utility by Visit interaction, with Visit as the repeated factor.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    734
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.741
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.0017
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0119
         upper limit
    		 0.0085
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 48. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Utility (continuous), Treatment by Visit interaction, and Baseline EQ-5D Utility by Visit interaction, with Visit as the repeated factor.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    734
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.792
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.0015
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0094
         upper limit
    		 0.0123

    Secondary: Change from Baseline in EQ-5D-5L Thermometer scores at Week 24 and 48

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    End point title
    		 Change from Baseline in EQ-5D-5L Thermometer scores at Week 24 and 48
    End point description
    EEQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset. Baseline was the latest pre-dose assessment value (Day 1) and change from Baseline=post-dose value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable. Participants with data available at specified time points has been analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and at Weeks 24 and 48
    End point values
    		 DTG+3TC FDC TAF-based regimen
    Number of subjects analysed
    364 [68]
    369 [69]
    Units: Scores on a scale
    arithmetic mean (standard error)
        Week 24
    1.2 ( 0.49 )
    1.3 ( 0.44 )
        Week 48
    1.1 ( 0.52 )
    1.7 ( 0.43 )
    Notes
    [68] - ITT-E Population.
    [69] - ITT-E Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Week 24. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Thermometer (continuous), Treatment by Visit interaction, and Baseline EQ-5D Thermometer by Visit interaction, with Visit as the repeated factor.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    733
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.879
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 1.2
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Week 48. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Thermometer (continuous), Treatment by Visit interaction, and Baseline EQ-5D Thermometer by Visit interaction, with Visit as the repeated factor.
    Comparison groups
    DTG+3TC FDC v TAF-based regimen
    Number of subjects included in analysis
    733
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.414
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 0.8

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Non-SAEs and SAEs were collected from start of the study treatment (Day 1) up to Week 48.
    Adverse event reporting additional description
    Safety Population. One participant randomized to TBR received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen.”
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    DTG + 3TC
    Reporting group description
    		 Participants who were on a stable TBR and who had an HIV-1 ribonucleic acid (RNA) <50 copies per millilter (c/mL) at the time of screening, received fixed dose combination of DTG 50 milligrams (mg) + 3TC 300 mg once daily up to 48 weeks.

    Reporting group title
    Randomized to TBR but received TDF-based regimen
    Reporting group description
    		 Participant randomized to TBR arm who had HIV-1 RNA <50 c/mL at the time of screening, received TDF-based regimen instead of TAF-based regimen in error. Participant continued to receive TDF-regimen up to the Week 48 visit (participant withdrew from the study at Week 36).

    Reporting group title
    TAF Based Regimen
    Reporting group description
    		 Participants who were on a stable TBR and who had an HIV-1 RNA<50 c/mL at the time of screening, were continued to receive TBR up to 48 weeks.

    Serious adverse events
    		 DTG + 3TC Randomized to TBR but received TDF-based regimen TAF Based Regimen
    Total subjects affected by serious adverse events
         subjects affected / exposed
    21 / 369 (5.69%)
    0 / 1 (0.00%)
    16 / 371 (4.31%)
         number of deaths (all causes)
    1
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma pancreas
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diffuse large B-cell lymphoma
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Penile squamous cell carcinoma
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vasculitis
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Amniorrhoea
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian haematoma
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicidal ideation
         subjects affected / exposed
    2 / 369 (0.54%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femoral neck fracture
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gun shot wound
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral haematoma
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Facial paresis
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Inguinal hernia
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary dyskinesia
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteitis
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 369 (0.54%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Amniotic cavity infection
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Labyrinthitis
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis pneumococcal
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pertussis
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shigella infection
         subjects affected / exposed
    0 / 369 (0.00%)
    0 / 1 (0.00%)
    1 / 371 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    1 / 369 (0.27%)
    0 / 1 (0.00%)
    0 / 371 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 DTG + 3TC Randomized to TBR but received TDF-based regimen TAF Based Regimen
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    222 / 369 (60.16%)
    1 / 1 (100.00%)
    204 / 371 (54.99%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    24 / 369 (6.50%)
    0 / 1 (0.00%)
    17 / 371 (4.58%)
         occurrences all number
    37
    0
    19
    Dizziness
         subjects affected / exposed
    8 / 369 (2.17%)
    0 / 1 (0.00%)
    8 / 371 (2.16%)
         occurrences all number
    8
    0
    8
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    20 / 369 (5.42%)
    0 / 1 (0.00%)
    3 / 371 (0.81%)
         occurrences all number
    20
    0
    3
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    12 / 369 (3.25%)
    0 / 1 (0.00%)
    3 / 371 (0.81%)
         occurrences all number
    13
    0
    4
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    30 / 369 (8.13%)
    1 / 1 (100.00%)
    26 / 371 (7.01%)
         occurrences all number
    34
    1
    28
    Nausea
         subjects affected / exposed
    15 / 369 (4.07%)
    0 / 1 (0.00%)
    7 / 371 (1.89%)
         occurrences all number
    16
    0
    7
    Abdominal pain
         subjects affected / exposed
    9 / 369 (2.44%)
    0 / 1 (0.00%)
    7 / 371 (1.89%)
         occurrences all number
    12
    0
    7
    Toothache
         subjects affected / exposed
    5 / 369 (1.36%)
    0 / 1 (0.00%)
    8 / 371 (2.16%)
         occurrences all number
    5
    0
    9
    Vomiting
         subjects affected / exposed
    8 / 369 (2.17%)
    0 / 1 (0.00%)
    4 / 371 (1.08%)
         occurrences all number
    8
    0
    4
    Constipation
         subjects affected / exposed
    8 / 369 (2.17%)
    0 / 1 (0.00%)
    2 / 371 (0.54%)
         occurrences all number
    9
    0
    2
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    4 / 369 (1.08%)
    0 / 1 (0.00%)
    8 / 371 (2.16%)
         occurrences all number
    4
    0
    8
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 369 (1.63%)
    0 / 1 (0.00%)
    9 / 371 (2.43%)
         occurrences all number
    6
    0
    9
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    16 / 369 (4.34%)
    0 / 1 (0.00%)
    9 / 371 (2.43%)
         occurrences all number
    16
    0
    10
    Depression
         subjects affected / exposed
    9 / 369 (2.44%)
    0 / 1 (0.00%)
    8 / 371 (2.16%)
         occurrences all number
    9
    0
    8
    Insomnia
         subjects affected / exposed
    10 / 369 (2.71%)
    0 / 1 (0.00%)
    7 / 371 (1.89%)
         occurrences all number
    10
    0
    7
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    21 / 369 (5.69%)
    0 / 1 (0.00%)
    28 / 371 (7.55%)
         occurrences all number
    22
    0
    31
    Arthralgia
         subjects affected / exposed
    12 / 369 (3.25%)
    0 / 1 (0.00%)
    13 / 371 (3.50%)
         occurrences all number
    12
    0
    13
    Pain in extremity
         subjects affected / exposed
    8 / 369 (2.17%)
    0 / 1 (0.00%)
    4 / 371 (1.08%)
         occurrences all number
    8
    0
    4
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    43 / 369 (11.65%)
    0 / 1 (0.00%)
    41 / 371 (11.05%)
         occurrences all number
    53
    0
    51
    Upper respiratory tract infection
         subjects affected / exposed
    31 / 369 (8.40%)
    1 / 1 (100.00%)
    32 / 371 (8.63%)
         occurrences all number
    42
    1
    38
    Syphilis
         subjects affected / exposed
    24 / 369 (6.50%)
    0 / 1 (0.00%)
    13 / 371 (3.50%)
         occurrences all number
    25
    0
    13
    Gastroenteritis
         subjects affected / exposed
    13 / 369 (3.52%)
    0 / 1 (0.00%)
    16 / 371 (4.31%)
         occurrences all number
    16
    0
    16
    Bronchitis
         subjects affected / exposed
    8 / 369 (2.17%)
    0 / 1 (0.00%)
    20 / 371 (5.39%)
         occurrences all number
    8
    0
    21
    Pharyngitis
         subjects affected / exposed
    14 / 369 (3.79%)
    0 / 1 (0.00%)
    11 / 371 (2.96%)
         occurrences all number
    15
    0
    12
    Anal chlamydia infection
         subjects affected / exposed
    8 / 369 (2.17%)
    0 / 1 (0.00%)
    12 / 371 (3.23%)
         occurrences all number
    9
    0
    16
    Influenza
         subjects affected / exposed
    9 / 369 (2.44%)
    0 / 1 (0.00%)
    8 / 371 (2.16%)
         occurrences all number
    9
    0
    8
    Urinary tract infection
         subjects affected / exposed
    6 / 369 (1.63%)
    0 / 1 (0.00%)
    8 / 371 (2.16%)
         occurrences all number
    8
    0
    10
    Urethritis
         subjects affected / exposed
    9 / 369 (2.44%)
    0 / 1 (0.00%)
    4 / 371 (1.08%)
         occurrences all number
    9
    0
    4
    Oral herpes
         subjects affected / exposed
    3 / 369 (0.81%)
    0 / 1 (0.00%)
    8 / 371 (2.16%)
         occurrences all number
    3
    0
    8
    Proctitis gonococcal
         subjects affected / exposed
    8 / 369 (2.17%)
    0 / 1 (0.00%)
    3 / 371 (0.81%)
         occurrences all number
    9
    0
    5
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    12 / 369 (3.25%)
    0 / 1 (0.00%)
    11 / 371 (2.96%)
         occurrences all number
    12
    0
    11

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 May 2017
    Amendment 01: TAF was corrected by removal of the word “fumarate”. Clarification was provided in the overall design to specify that participants randomized to TBR will switch to DTG/3TC FDC at Week 52 if human immunodeficiency virus-1 ribonucleic acid (HIV-1 RNA) <50 copies per milliliter (c/mL) at Week 48 (or upon retest by Week 52). Biomarkers of inflammation and mitochondrial function were removed as exploratory endpoints. A Week 96 endpoint was added to the measurement of biomarkers of telomerase function in a subset of participants. Cardiovascular biomarker measurements were removed as exploratory endpoints. Inclusion Criteria #5 was edited for clarity. Protocol Section 6.2, Protocol Permitted Substitutions, added. The text defining the TBR comparators as investigational medicinal product was removed; TBR comparators are provided in designated, specific countries only, as needed. The Time and Events Table was modified to clarify that whole blood samples could be utilized for virology and for telomere length measurements, and cryopreserved peripheral blood mononuclear cells (PBMCs) could be used to evaluate telomerase activity. Updated version of Division of acquires immunodeficiency syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (version 2.1), March 2017, was provided in Protocol Section 12.9. Changes were made to the protocol text to reflect the addition of Country Specific requirements for Japan.
    13 Jun 2017
    Amendment 02: The impetus for this protocol amendment was to update Protocol Appendix 5, Protocol Appendix 6 and Protocol Appendix 8 based on the ViiV Healthcare templates for these appendices that were appropriate for the HIV participant population.
    24 Aug 2017
    Amendment 03: Amended to include: Addition of cluster of differentiation 8 plus (CD8+) lymphocyte assessments, addition of inflammatory biomarkers assessments as new exploratory endpoints, and revision of the sample size based on updated estimates for the primary endpoint for the investigational arm.
    07 Dec 2017
    Amendment 04: Amended to include pharmacokinetics assessments in the DTG/3TC FDC arm as exploratory endpoints; to update exclusion criterion 18 and remove its corresponding secondary endpoint no longer relevant; and to add glycated hemoglobin (HbA1c) and homeostasis model of assessment-insulin resistance (HOMA-IR) assessments. For clarification purposes, the adverse event (AE) severity grading in Protocol Appendix 8 and Protocol Section 13.8.6 (Evaluating AEs and serious adverse events [SAEs]) were updated to be consistent with Protocol Appendix 9, Protocol Section 13.9 (Division of AIDS table for Grading Severity of Adult and Pediatric Adverse Events). This change has no impact on the investigator’s evaluation of adverse events. Text was edited in Protocol Appendix 10, Protocol Section 13.10.2 to clarify wording for the country specific requirement for Japan.
    14 Jun 2018
    Amendment 05: Changes were made to the protocol to manage and mitigate risks following identification of a potential safety issue related to neural tube defects in infants born to women with exposure to DTG at the time of conception. Changes were also made to include updated text to address a higher number of participants screened than planned, to update references to the DTG Investigator’s Brochure (IB) to reflect the most current versions and to add clarification and correct minor typos. The Risk Assessment table (Protocol Section 4.6.1) was updated to include language regarding risk and mitigation of neural tube defects. The withdrawal criteria (Protocol Section 5.4) were updated to include a reminder that females of reproductive potential who change their minds and desire to be pregnant, or who state they no longer are willing to comply with the approved pregnancy avoidance methods, would also be withdrawn from the study. The Time and Events table (Protocol Section 7.1) was updated to include a reminder for investigators to check at every visit that females of reproductive potential are avoiding pregnancy. The modified list of highly effective methods for avoiding pregnancy in females of reproductive potential (FRP) (Protocol Section 13.3.1) was updated to exclude the double barrier method of contraception, which does not meet the updated GlaxoSmithKline [GSK]/ViiV criteria for a highly effective method. The Type and Number of participants (Protocol Section 4.3) and Sample Size Assumptions (Protocol Section 9.2.1) were updated to address a higher number of participants screened than planned.
    29 Aug 2018
    Amendment 06: Changes were made to the protocol to update the study design to extend the Randomized Early Switch Phase through to 148 weeks instead of Week 52, delaying the late switch to Week 148 with long-term follow-up through to completion of the study at Week 200. The rationale for this change was to collect and assess long-term comparative efficacy and safety data for DTG/3TC FDC vs. a TAF-based regimen.

    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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