A Dose Ranging Trial of GSK1349572 and 2 NRTI in HIV-1 Infected, Therapy Naive Subjects (ING112276)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00951015
First received: July 30, 2009
Last updated: December 19, 2013
Last verified: October 2013
Results First Received: August 22, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Infection, Human Immunodeficiency Virus
Interventions: Drug: GSK1349572
Drug: efavirenz

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible participants (par.) were randomized (ran) to receive Dolutegravir (DTG) (3 dose groups) or Efavirenz for 96 weeks. At Week 96, par. ran. to any dose of DTG entered an open-label phase and continued to receive DTG at the selected dose of 50 milligrams. A total of 208 par. were ran., and 205 received at least one dose of study medication.

Reporting Groups
  Description
DTG 10 mg OD Participants received Dolutegravir (DTG) 10 milligrams (mg), DTG matching placebo, and Abacavir (ABC)/Lamivudine (3TC) 600 mg/300 mg or Tenofovir (TDF)/Emtricitabine (FTC) 300 mg/200 mg orally once daily (OD) for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Participant Flow:   Overall Study
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
STARTED     53     51     51     50  
Ongoing     47     45     46     8  
COMPLETED     0     0     0     32  
NOT COMPLETED     53     51     51     18  
Adverse Event                 1                 1                 2                 5  
Lack of Efficacy                 1                 1                 0                 0  
Protocol Violation                 1                 1                 1                 0  
Protocol-Defined Stopping Criteria                 0                 0                 0                 1  
Lost to Follow-up                 0                 2                 1                 2  
Withdrawal by Subject                 3                 1                 1                 2  
Ongoing                 47                 45                 46                 8  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
DTG 10 mg OD Participants received Dolutegravir (DTG) 10 milligrams (mg), DTG matching placebo, and Abacavir (ABC)/Lamivudine (3TC) 600 mg/300 mg or Tenofovir (TDF)/Emtricitabine (FTC) 300 mg/200 mg orally once daily (OD) for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.
Total Total of all reporting groups

Baseline Measures
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD     Total  
Number of Participants  
[units: participants]
  53     51     51     50     205  
Age  
[units: Years]
Mean ± Standard Deviation
  34.2  ± 9.25     37.0  ± 9.79     37.0  ± 8.89     40.7  ± 11.19     37.2  ± 10.00  
Gender  
[units: Participants]
         
Female     11     5     6     6     28  
Male     42     46     45     44     177  
Race/Ethnicity, Customized  
[units: participants]
         
African American/African Heritage (HER)     7     6     8     4     25  
American Indian or Alaska Native     1     3     4     2     10  
Japanese/East Asian HER/South East Asian HER     0     0     0     1     1  
Native Hawaiian or other Pacific Islander     3     0     0     0     3  
White     41     42     38     43     164  
African American/African HER & White     0     0     1     0     1  
Asian & White     1     0     0     0     1  



  Outcome Measures
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1.  Primary:   Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16   [ Time Frame: Week 16 ]

Measure Type Primary
Measure Title Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16
Measure Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Week 16. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason. Data are reported per the Week 16 report. In later cuts of the data, the Week 16 values may have changed (because of the nature of the TLOVR algorithm).
Time Frame Week 16  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat Exposed (ITT-E) Population: all randomized participants who received at least one dose of study medication

Reporting Groups
  Description
DTG 10 mg OD Participants received Dolutegravir (DTG) 10 milligrams (mg), DTG matching placebo, and Abacavir (ABC)/Lamivudine (3TC) 600 mg/300 mg or Tenofovir (TDF)/Emtricitabine (FTC) 300 mg/200 mg orally once daily (OD) for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  53     51     51     50  
Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16  
[units: participants]
  51     47     46     30  

No statistical analysis provided for Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16



2.  Secondary:   Viral Change Over the Initial 2 Weeks of Treatment   [ Time Frame: Baseline and Week 2 ]

Measure Type Secondary
Measure Title Viral Change Over the Initial 2 Weeks of Treatment
Measure Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline and Week 2. Viral change is defined as the change in plasma HIV-1 RNA over the initial 2 weeks of treatment, calculated as the value at Week 2 minus the value at Baseline.
Time Frame Baseline and Week 2  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT-E Population. Only those participants available at the specified time point were analyzed.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  53     50     50     48  
Viral Change Over the Initial 2 Weeks of Treatment  
[units: log10 c/mL]
Mean ± Standard Deviation
  -2.387  ± 0.4595     -2.365  ± 0.5458     -2.392  ± 0.4241     -1.930  ± 0.4312  

No statistical analysis provided for Viral Change Over the Initial 2 Weeks of Treatment



3.  Secondary:   Change From Baseline in HIV-1 RNA at the Indicated Time Points   [ Time Frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 ]

Measure Type Secondary
Measure Title Change From Baseline in HIV-1 RNA at the Indicated Time Points
Measure Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  53     51     51     50  
Change From Baseline in HIV-1 RNA at the Indicated Time Points  
[units: log10 c/mL]
Mean ± Standard Deviation
       
Week 1, n=53, 50, 48, 50     -1.815  ± 0.3999     -1.773  ± 0.4650     -1.738  ± 0.3840     -1.562  ± 0.4158  
Week 2, n=53, 50, 50, 48     -2.387  ± 0.4595     -2.365  ± 0.5458     -2.392  ± 0.4241     -1.930  ± 0.4312  
Week 4, n=53, 50, 50, 45     -2.629  ± 0.5863     -2.583  ± 0.6337     -2.713  ± 0.5471     -2.162  ± 0.5400  
Week 8, n=52, 50, 49, 45     -2.657  ± 0.6980     -2.666  ± 0.6667     -2.848  ± 0.6556     -2.450  ± 0.5989  
Week 12, n=53, 49, 49, 45     -2.685  ± 0.6831     -2.671  ± 0.6850     -2.860  ± 0.6772     -2.603  ± 0.5869  
Week 16, n=52, 49, 49, 45     -2.718  ± 0.6593     -2.668  ± 0.6826     -2.859  ± 0.6876     -2.698  ± 0.6715  
Week 20, n=52, 48, 49, 44     -2.701  ± 0.6423     -2.662  ± 0.6908     -2.869  ± 0.6896     -2.745  ± 0.6602  
Week 24, n=52, 49, 48, 45     -2.700  ± 0.6261     -2.657  ± 0.6969     -2.853  ± 0.6889     -2.773  ± 0.7026  
Week 32, n=52, 49, 47, 45     -2.717  ± 0.6588     -2.658  ± 0.6991     -2.855  ± 0.6963     -2.772  ± 0.7021  
Week 40, n=51, 48, 47, 44     -2.647  ± 0.7039     -2.665  ± 0.7051     -2.855  ± 0.6934     -2.795  ± 0.7169  
Week 48, n=51, 48, 48, 45     -2.723  ± 0.6519     -2.667  ± 0.6934     -2.850  ± 0.6849     -2.711  ± 0.7765  
Week 60, n=50, 48, 48, 44     -2.741  ± 0.6444     -2.675  ± 0.7012     -2.825  ± 0.7458     -2.765  ± 0.7035  
Week 72, n=51, 47, 48, 44     -2.742  ± 0.6453     -2.622  ± 0.8052     -2.860  ± 0.6930     -2.757  ± 0.7094  
Week 84, n=51, 47, 47, 43     -2.725  ± 0.6506     -2.670  ± 0.7064     -2.855  ± 0.6923     -2.743  ± 0.7321  
Week 96, n=48, 44, 46, 39     -2.728  ± 0.6494     -2.680  ± 0.7116     -2.854  ± 0.7061     -2.807  ± 0.7238  

No statistical analysis provided for Change From Baseline in HIV-1 RNA at the Indicated Time Points



4.  Secondary:   Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points   [ Time Frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 ]

Measure Type Secondary
Measure Title Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points
Measure Description Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  53     51     51     50  
Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points  
[units: Cells per cubic millimeter]
Median ( Inter-Quartile Range )
       
Week 1, n=53, 50, 48, 50     85.0  
  ( 18.0 to 134.0 )  
  94.5  
  ( 40.0 to 160.0 )  
  75.5  
  ( 18.5 to 129.5 )  
  42.5  
  ( -23.0 to 111.0 )  
Week 2, n=53, 50, 50, 47     75.0  
  ( 37.0 to 124.0 )  
  79.0  
  ( 27.0 to 138.0 )  
  99.5  
  ( 53.0 to 160.0 )  
  55.0  
  ( -10.0 to 132.0 )  
Week 4, n=53, 50, 50, 45     75.0  
  ( 34.0 to 151.0 )  
  89.0  
  ( 36.0 to 165.0 )  
  110.0  
  ( 46.0 to 170.0 )  
  89.0  
  ( 30.0 to 165.0 )  
Week 8, n=52, 50, 49, 44     118.5  
  ( 65.5 to 210.5 )  
  156.5  
  ( 93.0 to 226.0 )  
  129.0  
  ( 105.0 to 201.0 )  
  104.5  
  ( 34.5 to 240.5 )  
Week 12, n=53, 48, 48, 45     139.0  
  ( 96.0 to 284.0 )  
  137.5  
  ( 61.0 to 250.0 )  
  171.5  
  ( 107.5 to 269.0 )  
  127.0  
  ( 58.0 to 186.0 )  
Week 16, n=52, 49, 49, 44     153.0  
  ( 95.0 to 276.0 )  
  176.0  
  ( 86.0 to 227.0 )  
  160.0  
  ( 94.0 to 227.0 )  
  115.5  
  ( 65.5 to 226.0 )  
Week 20, n=52, 48, 49, 44     163.5  
  ( 79.5 to 288.5 )  
  200.0  
  ( 103.0 to 316.5 )  
  139.0  
  ( 64.0 to 238.0 )  
  136.0  
  ( 54.5 to 215.5 )  
Week 24, n=51, 49, 47, 44     159.0  
  ( 97.0 to 233.0 )  
  206.0  
  ( 102.0 to 289.0 )  
  167.0  
  ( 125.0 to 268.0 )  
  109.5  
  ( 66.0 to 229.0 )  
Week 32, n=50, 48, 47, 44     221.5  
  ( 94.0 to 300.0 )  
  195.5  
  ( 109.0 to 294.0 )  
  203.0  
  ( 125.0 to 282.0 )  
  146.5  
  ( 82.5 to 223.5 )  
Week 40, n=50, 48, 47, 44     205.0  
  ( 136.0 to 364.0 )  
  204.5  
  ( 157.5 to 346.5 )  
  224.0  
  ( 123.0 to 322.0 )  
  171.5  
  ( 123.0 to 268.0 )  
Week 48, n=51, 47, 47, 45     204.0  
  ( 127.0 to 384.0 )  
  249.0  
  ( 143.0 to 416.0 )  
  223.0  
  ( 141.0 to 292.0 )  
  174.0  
  ( 91.0 to 292.0 )  
Week 60, n=51, 48, 47, 43     265.0  
  ( 173.0 to 365.0 )  
  278.0  
  ( 198.5 to 369.5 )  
  229.0  
  ( 166.0 to 306.0 )  
  221.0  
  ( 153.0 to 355.0 )  
Week 72, n=51, 47, 48, 44     236.0  
  ( 177.0 to 351.0 )  
  285.0  
  ( 186.0 to 427.0 )  
  220.0  
  ( 146.0 to 373.0 )  
  195.0  
  ( 144.0 to 334.5 )  
Week 84, n=51, 47, 46, 42     292.0  
  ( 222.0 to 408.0 )  
  313.0  
  ( 244.0 to 366.0 )  
  280.0  
  ( 197.0 to 379.0 )  
  296.5  
  ( 187.0 to 400.0 )  
Week 96, n=48, 44, 46, 39     335.0  
  ( 253.5 to 478.5 )  
  391.5  
  ( 243.0 to 527.0 )  
  326.0  
  ( 236.0 to 451.0 )  
  301.0  
  ( 204.0 to 445.0 )  

No statistical analysis provided for Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points



5.  Secondary:   Number of Participants With New HIV-associated Conditions of the Indicated Class   [ Time Frame: From Baseline up to Week 96 ]

Measure Type Secondary
Measure Title Number of Participants With New HIV-associated Conditions of the Indicated Class
Measure Description HIV-associated conditions were assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the acquired immunodeficiency syndrome (AIDS) surveillance case definition.
Time Frame From Baseline up to Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT-E Population

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  53     51     51     50  
Number of Participants With New HIV-associated Conditions of the Indicated Class  
[units: participants]
       
Category B     2     0     1     1  
Category C     0     0     1     0  
Death     1     0     0     0  

No statistical analysis provided for Number of Participants With New HIV-associated Conditions of the Indicated Class



6.  Secondary:   Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death)   [ Time Frame: From Baseline up to Week 96 ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death)
Measure Description Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CAT A at Baseline (BS) to CAT B event (EV), CAT A at BS to a CAT C EV; CAT B at BS to a CAT C EV; CAT C at BS to a new CAT C EV; or CAT A, B, or C at BS to death.
Time Frame From Baseline up to Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT-E Population

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  53     51     51     50  
Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death)  
[units: participants]
       
CAT A at Baseline to a CAT C event     0     0     0     0  
CAT B at Baseline to a CAT C event     0     0     1     0  
CAT C at Baseline to a new CAT C event     0     0     0     0  
CAT A, B, or C at Baseline to death     1     0     0     0  

No statistical analysis provided for Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death)



7.  Secondary:   Number of Participants With Plasma HIV-1 RNA <50 c/mL   [ Time Frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 ]

Measure Type Secondary
Measure Title Number of Participants With Plasma HIV-1 RNA <50 c/mL
Measure Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<50 copies/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT-E Population

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  53     51     51     50  
Number of Participants With Plasma HIV-1 RNA <50 c/mL  
[units: participants]
       
Baseline     0     0     0     0  
Week 1     6     4     4     3  
Week 2     22     19     11     6  
Week 4     37     35     31     9  
Week 8     46     45     43     18  
Week 12     50     46     45     25  
Week 16     51     46     47     29  
Week 20     51     47     47     38  
Week 24     51     46     47     41  
Week 32     50     45     46     43  
Week 40     49     45     46     42  
Week 48     48     45     46     40  
Week 60     48     44     46     41  
Week 72     48     44     45     40  
Week 84     47     43     46     38  
Week 96     42     40     45     36  

No statistical analysis provided for Number of Participants With Plasma HIV-1 RNA <50 c/mL



8.  Secondary:   Number of Participants With Plasma HIV-1 RNA <400 c/mL   [ Time Frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 ]

Measure Type Secondary
Measure Title Number of Participants With Plasma HIV-1 RNA <400 c/mL
Measure Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. The analysis was performed using the time to loss of virological response (TLOVR) dataset. In the TLOVR dataset, participant responses at a specified threshold of HIV-1 RNA (<400 c/mL) are determined by using the Food and Drug Administration's TLOVR algorithm. Using the TLOVR algorithm, participants are considered to have failed on therapy if they never achieved confirmed RNA levels below the threshold, if they had confirmed rebound of RNA above the threshold, if they made a non-permitted change in background regimen, or if they permanently discontinued investigational product for any reason.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT-E Population

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  53     51     51     50  
Number of Participants With Plasma HIV-1 RNA <400 c/mL  
[units: participants]
       
Baseline     0     0     0     0  
Week 1     25     20     16     15  
Week 2     45     45     41     23  
Week 4     52     49     48     32  
Week 8     52     49     49     41  
Week 12     52     49     49     45  
Week 16     52     48     49     45  
Week 20     52     48     49     45  
Week 24     52     47     48     45  
Week 32     52     47     48     45  
Week 40     50     47     48     45  
Week 48     50     47     48     44  
Week 60     50     46     48     44  
Week 72     50     46     47     43  
Week 84     50     45     47     42  
Week 96     46     43     46     39  

No statistical analysis provided for Number of Participants With Plasma HIV-1 RNA <400 c/mL



9.  Secondary:   Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE)   [ Time Frame: From Baseline up to Week 96/Early Withdrawal ]

Measure Type Secondary
Measure Title Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE)
Measure Description An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity; or is a congenital anomaly/birth defect. All clinically suspected cases of hypersensitivity reaction to abacavir in participants receiving abacavir/lamivudine were reported as SAEs. Medical or scientific judgment was to have been exercised in other situations. Refer to the general AE/SAE module for a list of AEs (occuring at a frequency threshold >=3%) and SAEs.
Time Frame From Baseline up to Week 96/Early Withdrawal  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  53     51     51     50  
Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE)  
[units: participants]
       
Any AE     50     46     46     46  
Any SAE     5     5     7     7  

No statistical analysis provided for Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE)



10.  Secondary:   Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities   [ Time Frame: From Baseline up to Week 96/Early Withdrawal ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities
Measure Description Blood samples were collected for the measurement of clinical chemistry and hematology parameters. Toxicities were graded for severity according to the Division of AIDS (DAIDS) toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening).
Time Frame From Baseline up to Week 96/Early Withdrawal  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Population

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  53     51     51     50  
Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities  
[units: participants]
       
Alanine amino transferase     7     11     3     19  
Cholesterol     18     16     13     24  
Creatinine kinase     17     6     7     5  
Lipase     11     13     11     9  
Triglycerides     0     1     2     1  
Alkaline phosphatase     1     0     1     10  
Amylase     2     3     1     4  
Aspartate amino transferase     12     8     6     9  
Carbon dioxide content/bicarbonate     28     24     23     30  
Creatinine     0     4     0     0  
Hypercalcemia     0     0     0     1  
Hyperglycaemia     16     15     17     17  
Hyperkalemia     0     0     1     1  
Hypernatremia     1     1     1     0  
Hypocalcemia     4     5     5     8  
Hypoglycaemia     3     3     5     4  
Hypokalemia     4     1     3     3  
Hyponatremia     6     12     7     13  
Low-density lipoprotein cholesterol     14     15     11     20  
Magnesium     7     6     5     4  
Phosphate, inorganic     9     15     14     11  
Total bilirubin     3     4     3     0  
Activated partial thromboplastin time     7     12     6     5  
Hemoglobin     0     1     0     1  
International normalized ratio     6     9     6     5  
Platelet count     1     4     1     1  
Prothrombin time     7     8     7     4  
Total neutrophils     9     7     6     10  
White blood cell count     1     1     1     1  

No statistical analysis provided for Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities



11.  Secondary:   Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance   [ Time Frame: From Baseline up to Week 96/Early Withdrawal ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance
Measure Description For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 without evidence of prior suppression to <400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.
Time Frame From Baseline up to Week 96/Early Withdrawal  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
On-treatment Genotypic Resistance Population: all participants in the ITT-E Population with available on-treatment genotypic data, excluding participants who were not protocol-defined virologic failures.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  2     1     0     1  
Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance  
[units: participants]
       
A23A/V     1     0         0  
S255N     1     0         0  

No statistical analysis provided for Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance



12.  Secondary:   Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance   [ Time Frame: From Baseline up to Week 96/Early Withdrawal ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance
Measure Description For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 without evidence of prior suppression to <400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.
Time Frame From Baseline up to Week 96/Early Withdrawal  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
On-treatment Genotypic Resistance Population: all participants in the ITT-E Population with available on-treatment genotypic data, excluding participants who were not protocol-defined virologic failures.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  2     1     0     1  
Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance  
[units: participants]
  1     0         0  

No statistical analysis provided for Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance



13.  Secondary:   Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance   [ Time Frame: From Baseline up to Week 96/Early Withdrawal ]

Measure Type Secondary
Measure Title Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance
Measure Description The FC in IC50 (50% inhibitory concentration) for DTG relative to wild-type virus was determined for virus isolated at Baseline and at the time of PDVF. Fold increase in DTG FC at the time of PDVF was derived as the PDVF FC/Baseline FC ratio. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 4, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 without evidence of prior suppression to <400copies/mL or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >0.5 log10 copies/mL above the nadir value, where nadir is the lowest HIV-1 value >=400 copies/mL.
Time Frame From Baseline up to Week 96/Early Withdrawal  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
On-treatment Phenotypic Resistance Population: all participants in the ITT-E Population with available on-treatment phenotypic data, excluding participants who were not protocol-defined virologic failures.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  2     1     0     0  
Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance  
[units: participants]
       
<1 fold     0     1          
1-<2 fold     2     0          
2-<4 fold     0     0          
4-<8 fold     0     0          
>=8 fold     0     0          

No statistical analysis provided for Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance



14.  Secondary:   Plasma DTG Concentration   [ Time Frame: Week 2, Week 12, and Week 24 ]

Measure Type Secondary
Measure Title Plasma DTG Concentration
Measure Description Blood samples for the determination of plasma DTG concentration were collected from the participants randomized to receive DTG, at the following time points: pre-dose and 2-4 hours post-dose at Weeks 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. The Pharmacokinetic (PK) Summary Population is comprised of all participants who received DTG and underwent intensive PK sampling or limited PK sampling during the study and provided evaluable DTG PK parameters.
Time Frame Week 2, Week 12, and Week 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Summary Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles).Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Summary Population.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  48     46     46     0  
Plasma DTG Concentration  
[units: Micrograms per milliliter (µg/mL)]
Mean ± Standard Deviation
       
Week 2, Pre-dose, n=46, 44, 43, 0     0.3580  ± 0.18321     0.6779  ± 0.44085     1.4044  ± 0.88041      
Week 2, 2-4 hours post-dose, n=31, 29, 29, 0     1.0121  ± 0.28125     1.9716  ± 0.71890     3.8414  ± 1.87405      
Week 12, Pre-dose, n= 46, 45, 44, 0     0.3648  ± 0.16791     0.5759  ± 0.32645     1.4169  ± 1.00152      
Week 12, 2-4 hours post-dose, n=48, 45, 45, 0     1.0374  ± 0.27517     1.7907  ± 0.70953     3.6056  ± 1.33862      
Week 24, Pre-dose, n=45, 44, 44, 0     0.3766  ± 0.23399     0.6636  ± 0.50767     1.4534  ± 0.94283      
Week 24, 2-4 hours post-dose, n=45, 45, 45, 0     1.0113  ± 0.34083     1.9021  ± 0.79430     3.5397  ± 1.36538      

No statistical analysis provided for Plasma DTG Concentration



15.  Secondary:   AUC(0-tau) of DTG   [ Time Frame: pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2 ]

Measure Type Secondary
Measure Title AUC(0-tau) of DTG
Measure Description The area under the time concentration curve over the dosing interval (AUC[0-tau]) of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time Frame pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Summary Population. Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  15     15     15     0  
AUC(0-tau) of DTG  
[units: Hours*µg/mL]
Geometric Mean ( Geometric Coefficient of Variation )
  16.0  
  ( 40% )  
  23.1  
  ( 48% )  
  48.1  
  ( 40% )  
   
   

No statistical analysis provided for AUC(0-tau) of DTG



16.  Secondary:   Cmax, Cmin, and Ctau of DTG   [ Time Frame: pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2 ]

Measure Type Secondary
Measure Title Cmax, Cmin, and Ctau of DTG
Measure Description The maximal concentration (Cmax), minimal concentration (Cmax), and concentration at the end of dosing interval (Ctau) of DTG were determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time Frame pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Summary Population. Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  15     15     15     0  
Cmax, Cmin, and Ctau of DTG  
[units: µg/mL]
Geometric Mean ( Geometric Coefficient of Variation )
       
Cmax     1.10  
  ( 37% )  
  1.71  
  ( 43% )  
  3.40  
  ( 27% )  
   
   
Cmin     0.33  
  ( 64% )  
  0.44  
  ( 68% )  
  0.94  
  ( 74% )  
   
   
Ctau     0.37  
  ( 55% )  
  0.45  
  ( 71% )  
  1.05  
  ( 72% )  
   
   

No statistical analysis provided for Cmax, Cmin, and Ctau of DTG



17.  Secondary:   C0 and C0 Avg of DTG   [ Time Frame: Week 2, Week 12, and Week 24 ]

Measure Type Secondary
Measure Title C0 and C0 Avg of DTG
Measure Description The plasma DTG pre-dose concentration (C0) of DTG was determined using limited/sparse PK sampling at Week 2, Week 12, and Week 24. C0 avg was calculated at Week 24 as the mean of the C0 of DTG at Week 2, Week 12, and Week 24. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time Frame Week 2, Week 12, and Week 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Summary Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the PK Summary Population.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  49     46     46     0  
C0 and C0 Avg of DTG  
[units: µg/mL]
Geometric Mean ( Geometric Coefficient of Variation )
       
C0, Week 2, n=46, 44, 43, 0     0.31  
  ( 58% )  
  0.57  
  ( 62% )  
  1.20  
  ( 61% )  
   
   
C0, Week 12, n=46, 45, 44, 0     0.33  
  ( 49% )  
  0.47  
  ( 77% )  
  1.13  
  ( 95% )  
   
   
C0, Week 24, n=45, 44, 44, 0     0.33  
  ( 67% )  
  0.57  
  ( 74% )  
  1.20  
  ( 74% )  
   
   
C0 avg, n=48, 46, 46, 0     0.34  
  ( 49% )  
  0.56  
  ( 61% )  
  1.25  
  ( 55% )  
   
   

No statistical analysis provided for C0 and C0 Avg of DTG



18.  Secondary:   Time to Maximal Drug Concentration (Tmax) of DTG   [ Time Frame: pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2 ]

Measure Type Secondary
Measure Title Time to Maximal Drug Concentration (Tmax) of DTG
Measure Description tmax of DTG was determined using non-compartmental analysis based on intensive PK sampling at the following time points: pre-dose; 2, 3, 4, 8, and 24 hours post-dose at Week 2. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time Frame pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Summary Population. Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  15     15     15     0  
Time to Maximal Drug Concentration (Tmax) of DTG  
[units: Hours]
Median ( Full Range )
  2.0  
  ( 2.0 to 4.0 )  
  2.0  
  ( 2.0 to 8.0 )  
  2.0  
  ( 1.9 to 4.0 )  
   
   

No statistical analysis provided for Time to Maximal Drug Concentration (Tmax) of DTG



19.  Secondary:   Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters   [ Time Frame: Week 2 ]

Measure Type Secondary
Measure Title Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters
Measure Description Relationships between Week 2 plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], and Ctau [concentration at the end of the dosing interval]) and the change from Baseline in plasma HIV-1 RNA at Week 2 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson’s correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between plasma HIV-1 RNA and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time Frame Week 2  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK/Pharmacodynamic (PD) Analysis Population: all participants with available PD measures (e.g., safety and/or efficacy data) and with evaluable DTG plasma concentration data considered suitable for investigation of relationship with the PD measures. Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.
Overall DTG All participants who received DTG in any DTG treatment group (DTG 10 mg OD, DTG 25 mg OD, and DTG 50 mg OD)

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD     Overall DTG  
Number of Participants Analyzed  
[units: participants]
  15     15     15     0     45  
Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters  
[units: Pearson's correlation coefficient]
         
AUC(0-tau)     0.426     -0.018     -0.258         -0.086  
Cmax     0.452     -0.051     -0.150         -0.055  
Ctau     0.273     -0.100     -0.263         -0.129  

No statistical analysis provided for Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters



20.  Secondary:   Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters   [ Time Frame: Week 96 ]

Measure Type Secondary
Measure Title Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters
Measure Description Relationships between plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], C0avg [average pre-dose concentration], and Ctau [concentration at the end of the dosing interval]) and the change from Baseline in CD4+ cell counts at Week 96 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson’s correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between CD4+ cell counts and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association.Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time Frame Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK/PD Analysis Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the PK/PD Analysis Population.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.
Overall DTG All participants who received DTG in any DTG treatment group (DTG 10 mg OD, DTG 25 mg OD, and DTG 50 mg OD)

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD     Overall DTG  
Number of Participants Analyzed  
[units: participants]
  50     46     46     0     142  
Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters  
[units: Pearson's correlation coefficient]
         
AUC(0-tau), n=13, 14, 15, 0     -0.100     0.379     0.008         -0.005  
Cmax, n=13, 14, 15, 0     -0.047     0.332     0.234         0.037  
C0avg, n=43, 40, 42, 0     -0.009     -0.013     0.206         -0.011  
Ctau, n=13, 14, 15, 0     -0.289     0.299     -0.074         -0.055  

No statistical analysis provided for Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters



21.  Secondary:   Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters   [ Time Frame: Week 96 ]

Measure Type Secondary
Measure Title Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters
Measure Description Relationships between log-transformed plasma DTG PK parameters (AUC[0-tau], Cmax, C0, C0avg, Ctau, and Cmin) and safety parameters (AE occurrence, maximum AE intensity, alanine aminotransferase [ALT], change from Baseline [CFB] in ALT, total bilirubin, CFB in total bilirubin, creatine kinase, CFB in creatine kinase, triglycerides, CFB in triglycerides, lipase, CFB in lipase, total cholesterol [TC], CFB in TC) was assessed using Pearson’s correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between safety parameters and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. The presence of >=1 AE was used for AE occurrence. The most severe AE grade/intensity was used for maximum AE intensity. Maximum laboratory values per participant were used for safety parameters. CFB was calculated as the post-Baseline value minus the value at Baseline.
Time Frame Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK/PD Analysis Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the PK/PD Analysis Population.

Reporting Groups
  Description
Overall DTG All participants who received DTG in any DTG treatment group (DTG 10 mg OD, DTG 25 mg OD, and DTG 50 mg OD)

Measured Values
    Overall DTG  
Number of Participants Analyzed  
[units: participants]
  142  
Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters  
[units: Pearson's correlation coefficient]
 
AUC(0-tau) versus AE occurrence, n=45     0.114  
AUC(0-tau) versus maximum AE intensity, n=45     0.171  
AUC(0-tau) versus ALT, n=45     -0.196  
AUC(0-tau) versus CFB in ALT, n=45     -0.201  
AUC(0-tau) versus total bilirubin, n=45     0.364  
AUC(0-tau) versus CFB in total bilirubin, n=45     0.147  
AUC(0-tau) versus creatine kinase, n=45     -0.168  
AUC(0-tau) versus CFB in creatine kinase, n=45     -0.145  
AUC(0-tau) vs Triglycerides, n=45     0.104  
AUC(0-tau) versus CFB in triglycerides, n=45     0.216  
AUC(0-tau) versus lipase, n=45     -0.066  
AUC(0-tau) versus CFB in lipase, n=45     0.092  
AUC(0-tau) versus total cholesterol, n=45     -0.097  
AUC(0-tau) versus CFB in total cholesterol, n=45     -0.153  
Cmax versus AE occurrence, n=45     0.061  
Cmax versus maximum AE intensity, n=45     0.110  
Cmax versus ALT, n=45     -0.135  
Cmax versus CFB in ALT, n=45     -0.135  
Cmax versus total bilirubin, n=45     0.265  
Cmax versus CFB in total bilirubin, n=45     0.033  
Cmax versus creatine kinase, n=45     -0.188  
Cmax versus CFB in creatine kinase, n=45     -0.161  
Cmax versus triglycerides, n=45     0.134  
Cmax versus CFB in triglycerides, n=45     0.244  
Cmax versus lipase, n=45     -0.034  
Cmax versus CFB in lipase, n=45     0.115  
Cmax versus total cholesterol, n=45     -0.101  
Cmax versus CFB in total cholesterol, n=45     -0.192  
C0 versus AE occurrence, n=133     -0.080  
C0 versus maximum AE intensity, n=133     -0.003  
C0 versus ALT, n=133     -0.196  
C0 versus CFB in ALT, n=133     -0.237  
C0 versus total bilirubin, n=133     0.298  
C0 versus CFB in total bilirubin, n=133     0.120  
C0 versus creatine kinase, n=133     -0.094  
C0 versus CFB in creatine kinase, n=133     -0.093  
C0 versus triglycerides, n=133     -0.058  
C0 versus CFB in triglycerides, n=133     -0.012  
C0 versus lipase, n=133     -0.187  
C0 versus CFB in lipase, n=133     -0.137  
C0 versus total cholesterol, n=133     -0.179  
C0 versus CFB in total cholesterol, n=133     -0.125  
C0avg versus AE occurrence, n=140     -0.028  
C0avg versus maximum AE intensity, n=140     0.036  
C0avg versus ALT, n=140     -0.166  
C0avg versus CFB in ALT, n=140     -0.177  
C0avg versus total bilirubin, n=140     0.319  
C0avg versus CFB in total bilirubin, n=140     0.109  
C0avg versus creatine kinase, n=140     -0.114  
C0avg versus CFB in creatine kinase, n=140     -0.110  
C0avg versus triglycerides, n=140     0.057  
C0avg versus CFB in triglycerides, n=140     0.092  
C0avg versus lipase, n=140     -0.164  
C0avg versus CFB in lipase, n=140     -0.120  
C0avg versus total cholesterol, n=140     -0.170  
C0avg versus CFB in total cholesterol, n=140     -0.083  
Ctau versus AE occurrence, n=45     0.190  
Ctau versus maximum AE intensity, n=45     0.205  
Ctau versus ALT, n=45     -0.281  
Ctau versus CFB in ALT, n=45     -0.285  
Ctau versus total bilirubin, n=45     0.446  
Ctau versus CFB in total bilirubin, n=45     0.237  
Ctau versus creatine kinase, n=45     -0.143  
Ctau versus CFB in creatine kinase, n=45     -0.125  
Ctau versus triglycerides, n=45     0.061  
Ctau versus CFB in triglycerides, n=45     0.172  
Ctau versus lipase, n=45     -0.131  
Ctau versus CFB in lipase, n=45     0.056  
Ctau versus total cholesterol, n=45     -0.039  
Ctau versus CFB in total cholesterol, n=45     -0.108  
Cmin versus AE occurrence, n=45     0.156  
Cmin versus maximum AE intensity, n=45     0.193  
Cmin versus ALT, n=45     -0.236  
Cmin versus CFB in ALT, n=45     -0.253  
Cmin versus total bilirubin, n=45     0.430  
Cmin versus CFB in total bilirubin, n=45     0.171  
Cmin versus creatine kinase, n=45     -0.132  
Cmin versus CFB in creatine kinase, n=45     -0.124  
Cmin versus triglycerides, n=45     -0.042  
Cmin versus CFB in triglycerides, n=45     0.057  
Cmin versus lipase, n=45     -0.135  
Cmin versus CFB in lipase, n=45     0.032  
Cmin versus total cholesterol, n=45     -0.194  
Cmin versus CFB in total cholesterol, n=45     -0.208  

No statistical analysis provided for Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters



22.  Secondary:   Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters   [ Time Frame: Week 96 ]

Measure Type Secondary
Measure Title Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters
Measure Description Logistic regressions were performed to examine the correlation between plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], Ctau [concentration at the end of the dosing interval], and C0avg [average pre-dose concentration]) on log scales and the presence of gastrointestinal system organ class AEs (abdominal pain, diarrhea, nausea, and vomiting) at Week 96. Data are presented as estimates from logistic regression, which is a measure of the association between AEs of special interest and plasma DTG PK parameters. A value of 0 indicates no statistical association; a large absolute value of the estimate indicates higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed. Results are presented for participants in any DTG group (overall DTG).
Time Frame Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK/PD Analysis Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the PK/PD Analysis Population.

Reporting Groups
  Description
Overall DTG All participants who received DTG in any DTG treatment group (DTG 10 mg OD, DTG 25 mg OD, and DTG 50 mg OD).

Measured Values
    Overall DTG  
Number of Participants Analyzed  
[units: participants]
  142  
Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters  
[units: estimated effect]
 
Abdominal pain versus AUC(0-tau), n=45     -2.49  
Abdominal pain versus Cmax, n=45     -2.98  
Abdominal pain versus Ctau, n=45     -1.72  
Abdominal pain versus C0avg, n=140     -0.41  
Diarrhoea versus AUC(0-tau), n=45     -0.62  
Diarrhoea versus Cmax, n=45     -0.98  
Diarrhoea versus Ctau, n=45     -0.29  
Diarrhoea versus C0avg, n=140     0.13  
Nausea versus AUC(0-tau), n=45     -0.31  
Nausea versus Cmax, n=45     -0.72  
Nausea versus Ctau, n=45     0.03  
Nausea versus C0avg, n=140     -0.32  
Vomiting versus AUC(0-tau), n=45     -1.29  
Vomiting versus Cmax, n=45     -1.61  
Vomiting versus Ctau, n=45     -1.15  
Vomiting versus C0avg, n=140     -0.89  

No statistical analysis provided for Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters



23.  Other Pre-specified:   Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at the Indicated Time Points   [ Time Frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 ]

Measure Type Other Pre-specified
Measure Title Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at the Indicated Time Points
Measure Description Change from Baseline in CD8+ cell count data are not available; CD8+ data are only listed on a per-participant basis and were not summarized.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT-E Population

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
Number of Participants Analyzed  
[units: participants]
  0     0     0     0  
Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at the Indicated Time Points                  

No statistical analysis provided for Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at the Indicated Time Points




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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