Trial Outcomes & Findings for Dolutegravir Compared to Darunavir/Ritonavir , Each in Combination With Dual Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in ART-naive Subjects (NCT NCT01449929)

Last Updated: 2018-01-16

Results Overview

Assessment was done using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm.This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks). Modified Intent-To-Treat Exposed (mITT-E) Population:all randomized participants who received at least one dose of investigational product

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

488 participants

Primary outcome timeframe

Week 48

Results posted on

2018-01-16

Participant Flow

This was a 2 sequential treatment period study. In first period (Randomization phase) participants received either dolutegravir (DTG) 50 milligram (mg) or darunavir (DRV) 800 mg with ritonavir (RTV) 100 mg once daily (QD) for 96 weeks. DTG participants who completed 96 Weeks of DTG then continued to receive DTG 50 mg in Extension phase.

A total of 595 participants were screened; 107 were screen failures; 488 were randomized; 485 received at least 1 dose of study medication and comprised the Intent-To-Treat exposed (ITT-E) population of which 1 participant was removed, creating the modified ITT-E population with 484 participants. 123 participants enrolled in Extension Phase.

Participant milestones

Participant milestones
Measure	DTG 50 mg QD Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.	Extension DTG 50 mg DTG participants who successfully completed 96 Weeks of randomized phase continued to receive DTG 50 mg QD during Extension phase
Randomization Phase 96 Week STARTED	242	242	0
Randomization Phase 96 Week COMPLETED	209	189	0
Randomization Phase 96 Week NOT COMPLETED	33	53	0
Extension Phase Approximately 3 Years STARTED	0	0	123
Extension Phase Approximately 3 Years COMPLETED	0	0	115
Extension Phase Approximately 3 Years NOT COMPLETED	0	0	8

Reasons for withdrawal

Reasons for withdrawal
Measure	DTG 50 mg QD Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.	Extension DTG 50 mg DTG participants who successfully completed 96 Weeks of randomized phase continued to receive DTG 50 mg QD during Extension phase
Randomization Phase 96 Week Adverse Event	5	13	0
Randomization Phase 96 Week Lack of Efficacy	3	4	0
Randomization Phase 96 Week Protocol Violation	5	6	0
Randomization Phase 96 Week Protocol-defined Stopping Criteria	1	0	0
Randomization Phase 96 Week Lost to Follow-up	15	18	0
Randomization Phase 96 Week Withdrawal by Subject	2	8	0
Randomization Phase 96 Week Physician Decision	2	3	0
Randomization Phase 96 Week Other: study closed/terminated	0	1	0
Extension Phase Approximately 3 Years Adverse Event	0	0	2
Extension Phase Approximately 3 Years Lack of Efficacy	0	0	2
Extension Phase Approximately 3 Years Lost to Follow-up	0	0	4

Baseline Characteristics

Dolutegravir Compared to Darunavir/Ritonavir , Each in Combination With Dual Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in ART-naive Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.	Total n=484 Participants Total of all reporting groups
Age, Continuous	35.7 Years STANDARD_DEVIATION 10.66 • n=5 Participants	36.2 Years STANDARD_DEVIATION 10.64 • n=7 Participants	35.9 Years STANDARD_DEVIATION 10.64 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	41 Participants n=7 Participants	72 Participants n=5 Participants
Sex: Female, Male Male	211 Participants n=5 Participants	201 Participants n=7 Participants	412 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	60 Participants n=5 Participants	53 Participants n=7 Participants	113 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	169 Participants n=5 Participants	173 Participants n=7 Participants	342 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: mITT-E Population

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48	90 Percentage of participants	83 Percentage of participants

SECONDARY outcome

Timeframe: From Baseline through Week 48

Population: mITT-E Population

The time to viral suppression (i.e. first viral load value \<50 copies/mL) through Week 48 was derived and summarized using Kaplan-Meier plots. Participants who withdrew for any reason without having suppressed prior to the analysis were censored. Confidence intervals were estimated using the Brookmeyer-Crowley method.

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Time to Virologic Suppression (<50 Copies/mL) Through Week 48	28.0 Days The DTG median time to suppression 95% CI was not estimable due to the steep increase in cumulative incidence at Day 28, so the confidence limit lines do not extend to cross the median line.	85.0 Days Interval 84.0 to 108.0

SECONDARY outcome

Timeframe: Week 48

Population: mITT-E Population

The percentage of participants with Plasma HIV-1 RNA \<400 c/mL at Week 48 was assessed MSDF, as codified by the FDA "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks).

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Percentage of Participants With Plasma HIV-1 RNA <400 c/mL at Week 48	92 Percentage of participants	87 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 24, 36 and 48

Population: mITT-E Population.

Change from Baseline in plasma HIV-1 RNA (log10 c/mL) was assessed at Weeks 4, 8, 12, 16, 24, 36 and 48 . Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the mITT-E Population.

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 Week 4, n=238, 235	-2.80 Log10 copies per mL Standard Deviation 0.625	-2.01 Log10 copies per mL Standard Deviation 0.454
Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 Week 8, n=237, 236	-2.86 Log10 copies per mL Standard Deviation 0.649	-2.40 Log10 copies per mL Standard Deviation 0.524
Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 Week 12, n=234, 227	-2.88 Log10 copies per mL Standard Deviation 0.653	-2.61 Log10 copies per mL Standard Deviation 0.537
Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 Week 16, n=229, 228	-2.86 Log10 copies per mL Standard Deviation 0.691	-2.71 Log10 copies per mL Standard Deviation 0.618
Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 Week 24, n=234, 227	-2.86 Log10 copies per mL Standard Deviation 0.765	-2.83 Log10 copies per mL Standard Deviation 0.663
Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 Week 36, n=232, 218	-2.87 Log10 copies per mL Standard Deviation 0.715	-2.85 Log10 copies per mL Standard Deviation 0.683
Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48 Week 48, n=227, 212	-2.89 Log10 copies per mL Standard Deviation 0.739	-2.86 Log10 copies per mL Standard Deviation 0.663

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 36 and 48 for CD4+ and Baseline and Weeks 4, 12, 24 and 48 for CD8+

Population: mITT-E Population.

Change from Baseline in CD4+ cell counts was assessed at Weeks 4, 8, 12, 16, 36 and 48. Change from Baseline in CD8+ cell counts was assessed at Weeks 4, 12, 24 and 48. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits and parameters, so the overall number of participants analyzed reflects everyone in the mITT-E Population.

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Change From Baseline in CD4+ and CD8+ Cell Counts CD4+ cell count, Week 4, n=237, 236	80.1 Cells per millimeters cubed (cells/mm^3) Standard Deviation 101.36	75.6 Cells per millimeters cubed (cells/mm^3) Standard Deviation 124.36
Change From Baseline in CD4+ and CD8+ Cell Counts CD4+ cell count, Week 8, n=236, 236	126.9 Cells per millimeters cubed (cells/mm^3) Standard Deviation 124.13	118.8 Cells per millimeters cubed (cells/mm^3) Standard Deviation 142.54
Change From Baseline in CD4+ and CD8+ Cell Counts CD4+ cell count, Week 12, n=234, 228	135.2 Cells per millimeters cubed (cells/mm^3) Standard Deviation 120.03	131.8 Cells per millimeters cubed (cells/mm^3) Standard Deviation 143.88
Change From Baseline in CD4+ and CD8+ Cell Counts CD4+ cell count, Week 16, n=227, 227	156.8 Cells per millimeters cubed (cells/mm^3) Standard Deviation 146.60	146.1 Cells per millimeters cubed (cells/mm^3) Standard Deviation 166.08
Change From Baseline in CD4+ and CD8+ Cell Counts CD4+ cell count, Week 24, n=233, 227	165.1 Cells per millimeters cubed (cells/mm^3) Standard Deviation 145.85	164.3 Cells per millimeters cubed (cells/mm^3) Standard Deviation 180.00
Change From Baseline in CD4+ and CD8+ Cell Counts CD4+ cell count, Week 36, n=232, 218	206.1 Cells per millimeters cubed (cells/mm^3) Standard Deviation 159.06	186.5 Cells per millimeters cubed (cells/mm^3) Standard Deviation 183.61
Change From Baseline in CD4+ and CD8+ Cell Counts CD4+ cell count, Week 48, n=227, 212	243.8 Cells per millimeters cubed (cells/mm^3) Standard Deviation 180.68	215.4 Cells per millimeters cubed (cells/mm^3) Standard Deviation 177.26
Change From Baseline in CD4+ and CD8+ Cell Counts CD8+ cell count, Week 4, n=235, 235	-47.4 Cells per millimeters cubed (cells/mm^3) Standard Deviation 276.01	-3.7 Cells per millimeters cubed (cells/mm^3) Standard Deviation 375.94
Change From Baseline in CD4+ and CD8+ Cell Counts CD8+ cell count, Week 12, n=231, 227	-42.0 Cells per millimeters cubed (cells/mm^3) Standard Deviation 343.81	-68.9 Cells per millimeters cubed (cells/mm^3) Standard Deviation 373.38
Change From Baseline in CD4+ and CD8+ Cell Counts CD8+ cell count, Week 24, n=231, 224	-108.0 Cells per millimeters cubed (cells/mm^3) Standard Deviation 350.03	-132.9 Cells per millimeters cubed (cells/mm^3) Standard Deviation 389.70
Change From Baseline in CD4+ and CD8+ Cell Counts CD8+ cell count, Week 48, n=224, 210	-109.5 Cells per millimeters cubed (cells/mm^3) Standard Deviation 360.94	-162.1 Cells per millimeters cubed (cells/mm^3) Standard Deviation 421.07

SECONDARY outcome

Timeframe: Week 48

Population: mITT-E Population

The number of participants with HIV-1 disease progression (AIDS or death) was assessed per the Centers for Disease Control and Prevention (CDC) 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. The CDC classifies HIV infection as Category A (participants with asymptomatic HIV infection, acute HIV infection with accompanying illness, or persistent generalized lymphadenopathy), Category B (participants with symptomatic non-AIDS condition, i.e., conditions that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection), and Category C (includes AIDS indicator conditions as defined by diagnostic or presumptive measures).

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Number of Participants With HIV-1 Associated Disease Progression With the Indicated Shift to CDC Class C, or New CDC Class C or Death at Week 48	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline through Week 48

Population: mSafety Population.

Fasting LDL cholesterol change from Baseline was analyzed. Values represented are for adjusted means. Estimates are calculated from a repeated measures model including the following covariates: treatment, visit, Baseline plasma HIV-1 RNA, background dual NRTI therapy, Baseline LDL cholesterol, treatment\*visit interaction and Baseline LDL cholesterol\*visit interaction. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=182 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=178 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Change From Baseline in Fasting Low-density Lipoprotein (LDL) Cholesterol Through Week 48	0.07 Millimoles per liter (mmol/L) Standard Error 0.041	0.37 Millimoles per liter (mmol/L) Standard Error 0.041

SECONDARY outcome

Timeframe: From Baseline through Week 48

Population: mSafety Population.

Hematology and clinical chemistry data were summarized according to the division of AIDS (DAIDS) table for grading the Severity of adverse events, version 1.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for which an increase in fasting LDL cholesterol to Grade 2 or higher occurred. Only those participants with data available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Percentage of Participants With Grade 2 or Higher Abnormalities in Fasting LDL Cholesterol Through Week 48	2 Percentage of Participants	7 Percentage of Participants

SECONDARY outcome

Timeframe: From Baseline through Week 48

Population: mSafety Population

Hematology and clinical chemistry data were summarized according to the division of AIDS (DAIDS) table for grading the Severity of adverse events, version 1.0. Grade 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred.

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Alanine Amino Transferase, G3	2 Participants	1 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Alanine Amino Transferase, G4	1 Participants	3 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Aspartate Amino Transferase, G3	6 Participants	3 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Aspartate Amino Transferase, G4	2 Participants	0 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Cholesterol, G3	0 Participants	3 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Creatine Kinase, G3	8 Participants	5 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Creatine Kinase, G4	8 Participants	4 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Hyperglycaemia, G3	1 Participants	2 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Hypoglycaemia, G3	0 Participants	1 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities LDL Cholesterol, G3	2 Participants	6 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Lipase, G3	5 Participants	5 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Lipase, G4	2 Participants	0 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Phosphorus, inorganic, G3	7 Participants	7 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Total Bilirubin, G3	1 Participants	0 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Triglycerides, G3	1 Participants	2 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Triglycerides, G4	0 Participants	1 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Hemoglobin, G3	1 Participants	0 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Hemoglobin, G4	1 Participants	0 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Platelet count, G4	0 Participants	1 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Total Neutrophils, G3	5 Participants	0 Participants
Number of Participants With the Indicated Grade 3 and Grade 4 Maximum Post-Baseline Chemistry and Hematology Laboratory Toxicities Total Neutrophils, G4	3 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline until PDVF up to Week 48

Population: PDVF Genotypic Population

An assessment was made of every change across all amino acids within the integrase (IN), reverse transcriptase (RT), and Protease (PRO) encoding region at Baseline and at time of suspected PDVF. PDVF is defined as the confirmed plasma HIV-1 RNA \>200 c/mL \>=Week 24. PDVF Genotypic Population included all participants in the mITT-E population with available on-treatment genotypic resistance data, at time of PDVF. Only those participants with data available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=2 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=2 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Number of Participants (Par.) With Detectable Virus That Has Genotypic or Phenotypic Evidence of Treatment-emergent Resistance to DTG, DRV+RTV and Other On-study ART at Time of Protocol Defined Virology Failure (PDVF)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 24, and Week 48

Population: mITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the mITT-E Population.

SDM is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Each item is rated from 0 to 4 where 0 (complete absence of symptom) and 4 (very bothersome symptom). Overall score calculated as the sum of the scores for each of the 20 items of the questionnaire and ranged from 0 (best health) and 80 (worst health). Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, baseline viral load, background dual NRTI therapy and baseline symptom bother score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicates a decline in a participant's quality of life over that period.

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 Week 4, n=218, 210	-3.20 Scores on a scale Standard Error 0.56	-2.19 Scores on a scale Standard Error 0.56
Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 Week 24, n=222, 214	-2.71 Scores on a scale Standard Error 0.64	-1.65 Scores on a scale Standard Error 0.65
Change From Baseline in Acquired Immune Deficiency Syndrome (AIDS) Clinical Trials Group (ACTG) Symptom Distress Module (SDM) Bother Score at Week 4, Week 24, and Week 48 Week 48, n= 222, 215	-2.46 Scores on a scale Standard Error 0.68	-0.77 Scores on a scale Standard Error 0.69

SECONDARY outcome

Timeframe: Baseline, Week 24, and Week 48

Population: mITT-E Population.

The EQ-5D is a 5-question quality of life instrument that provides a utility score and visual analogue scale score that describes the participants' health status. The primary reason for including the EQ-5D is to elicit utility values for potential cost-effectiveness analysis for submission to health technology assessment agencies. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, baseline viral load, background dual NRTI therapy and Baseline EQ-5D utility score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Utility Scores at Week 24 and Week 48 Week 24, n=217, 213	0.00 Scores on a scale Standard Error 0.012	0.02 Scores on a scale Standard Error 0.012
Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Utility Scores at Week 24 and Week 48 Week 48, n=224, 217	0.01 Scores on a scale Standard Error 0.012	0.01 Scores on a scale Standard Error 0.012

SECONDARY outcome

Timeframe: Baseline, Week 24, and Week 48

Population: mITT-E Population.

The European Quality of Life -5 Dimensions (EQ-5D) is a 5-question quality of life instrument that provides a utility score and visual analogue scale score that describes the participants' health status. The primary reason for including the EQ-5D is to elicit utility values for potential cost-effectiveness analysis for submission to health technology assessment agencies. Thermometer score is based on a visual analogue scale (VAS) ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).Values represented are for adjusted mean. Estimates are calculated from an ANCOVA model adjusting for age, sex, race, Baseline viral load, background dual NRTI therapy and Baseline EQ-5D thermometer score. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=242 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=242 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Change From Baseline in EQ-5D Thermometer Scores at Week 24 and Week 48 Week 24, n=221, 216	4.95 Scores on a scale Standard Error 0.885	5.96 Scores on a scale Standard Error 0.895
Change From Baseline in EQ-5D Thermometer Scores at Week 24 and Week 48 Week 48, n=224, 220	5.78 Scores on a scale Standard Error 0.762	6.95 Scores on a scale Standard Error 0.769

SECONDARY outcome

Timeframe: Week 4, Week 24, and Week 48

Population: HIVTSQ mITT-E Population.

Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The treatment satisfaction score (range: 0-60) was the sum of the individual items. HIVTSQ mITT-E Population=Only participants from USA, France, Germany, Italy, Spain for whom valid translations were available from the mITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population.

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=214 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=206 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 Week 4, n=206, 192	54.1 Scores on a scale Standard Deviation 6.43	52.4 Scores on a scale Standard Deviation 7.94
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 Week 24, n= 211, 200	56.1 Scores on a scale Standard Deviation 5.16	54.3 Scores on a scale Standard Deviation 6.94
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Total Score at Week 4, Week 24, and Week 48 Week 48, n=212, 201	56.1 Scores on a scale Standard Deviation 4.60	54.5 Scores on a scale Standard Deviation 6.78

SECONDARY outcome

Timeframe: Week 4, Week 24, and Week 48

Population: HIVTSQ mITT-E Population.

Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The lifestyle/ease score is the sum of items 4, 5, 6, 7 and 8 (range: 0-30). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population.

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=214 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=206 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 Week 4, n=202, 190	26.7 Scores on a scale Standard Deviation 3.61	25.8 Scores on a scale Standard Deviation 4.48
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 Week 24, n=210, 199	27.5 Scores on a scale Standard Deviation 3.16	26.6 Scores on a scale Standard Deviation 4.11
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Lifestyle/Ease Sub Score at Week 4, Week 24, and Week 48 Week 48, n=211, 201	27.6 Scores on a scale Standard Deviation 3.00	26.6 Scores on a scale Standard Deviation 4.11

SECONDARY outcome

Timeframe: Week 4, Week 24, and Week 48

Population: HIVTSQ mITT-E Population.

Participant treatment satisfaction was measured using the self-reported scale (HIVTSQ), which consists of 10 items (1-satisfaction, 2-HIV control, 3-adverse effects, 4-level of demand, 5-convenience, 6-flexibility, 7-knowledge, 8-life habits, 9-recommendability, and 10-willingness to continue). Items are scored from 0 (very dissatisfied) to 6 (very satisfied), other than item 4, which has an inverted score from 6 (very demanding) to 0 (very undemanding). The convenience score is the score for item 5 (range: 0-6). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different visits, so the overall number of participants analyzed reflects everyone in the HIVTSQ mITT-E population.

Outcome measures

Outcome measures
Measure	DTG 50 mg QD n=214 Participants Participants received DTG 50 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks. Participants were then given the opportunity to receive DTG 50 mg QD during an Extension Phase of the study.	DRV 800 mg + RTV 100 mg QD n=206 Participants Participants received DRV 800 mg + RTV 100 mg QD administered in combination with FDC dual NRTI therapy (either ABC/3TC or TDF/FTC) for 96 weeks.
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 Week 4, n=204, 190	5.6 Scores on a scale Standard Deviation 0.71	5.2 Scores on a scale Standard Deviation 1.11
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 Week 24, n=211, 200,	5.6 Scores on a scale Standard Deviation 0.64	5.4 Scores on a scale Standard Deviation 1.01
Human Immunodeficiency Virus Treatment Satisfaction Questionnaire (HIVTSQ) Convenience Score at Week 4, Week 24, and Week 48 Week 48, n=212, 201	5.7 Scores on a scale Standard Deviation 0.62	5.4 Scores on a scale Standard Deviation 1.02

Adverse Events

DTG 50mg QD

Serious events: 36 serious events

Other events: 221 other events

Deaths: 1 deaths

DRV 800 mg + RTV 100 mg QD

Serious events: 21 serious events

Other events: 214 other events

Deaths: 0 deaths

Extension DTG 50 mg

Serious events: 4 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER