Trial Outcomes & Findings for A Trial Comparing GSK1349572 50mg Once Daily to Raltegravir 400mg Twice Daily (NCT NCT01227824)

Last Updated: 2018-10-09

Results Overview

Percentage of participants with plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) with \<50 c/mL was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) snapshot algorithm. The algorithm treats all participants without HIV-1 RNA data as non-responders, as well as participants who switch their concomitant Antiretroviral Therapy (ART) prior to Week 48 as follows: background ART substitutions not permitted per study; background ART substitutions permitted per study 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 will be determined by the last available HIV-1 RNA assessment while the subject was on-treatment. Intent-to-Treat Exposed (ITT-E) Population comprised all randomized participants who received at least one dose of study medication.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

828 participants

Primary outcome timeframe

Baseline up to Week 48

Results posted on

2018-10-09

Participant Flow

This was a randomized, parallel group, non-inferiority study to demonstrate the antiviral activity of Dolutegravir. Participants were enrolled from 9 countries. Participants in Dolutegravir arm who completed 96 Weeks double-blind phase continued to receive Dolutegravir in open-label phase, until dolutegravir was locally available commercially.

Total 1035 participants were screened; 827 participants were randomized, and 822 participants entered the treatment period. Of the 5 participants who were randomized but not treated with investigational product, 4 withdrew consent and 1 was randomized in error. 338 participants were enrolled in open label phase to receive Dolutegravir.

Participant milestones

Participant milestones
Measure	DTG 50 mg Once a Day Participants received Dolutegravir (DTG) 50 milligrams (mg) once a day in combination with Nonnucleoside Reverse Transcriptase Inhibitor (NRTI) therapy, either with Abacavir (ABC)/Lamivudine (3TC) or Tenofovir (TDF)/Emtricitabine (FTC). Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID Participants received Raltegravir (RTG) 400 mg twice a day (BID) in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.	DTG 50 mg Once a Day (Open-label) Participants who successfully completed 96 weeks of double blind phase continued to receive DTG 50 mg once a day during open label phase, until dolutegravir was locally available commercially. Participants received DTG 50 mg once a day in combination with NRTI therapy, with either ABC/3TC or TDF/FTC.
Double-blind Phase: 96 Weeks Duration STARTED	411	411	0
Double-blind Phase: 96 Weeks Duration COMPLETED	304	332	0
Double-blind Phase: 96 Weeks Duration NOT COMPLETED	107	79	0
Open-label Phase: Median of 1267 Days STARTED	0	0	338
Open-label Phase: Median of 1267 Days COMPLETED	0	0	294
Open-label Phase: Median of 1267 Days NOT COMPLETED	0	0	44

Reasons for withdrawal

Reasons for withdrawal
Measure	DTG 50 mg Once a Day Participants received Dolutegravir (DTG) 50 milligrams (mg) once a day in combination with Nonnucleoside Reverse Transcriptase Inhibitor (NRTI) therapy, either with Abacavir (ABC)/Lamivudine (3TC) or Tenofovir (TDF)/Emtricitabine (FTC). Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID Participants received Raltegravir (RTG) 400 mg twice a day (BID) in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.	DTG 50 mg Once a Day (Open-label) Participants who successfully completed 96 weeks of double blind phase continued to receive DTG 50 mg once a day during open label phase, until dolutegravir was locally available commercially. Participants received DTG 50 mg once a day in combination with NRTI therapy, with either ABC/3TC or TDF/FTC.
Double-blind Phase: 96 Weeks Duration Adverse Event	12	7	0
Double-blind Phase: 96 Weeks Duration Lack of Efficacy	22	25	0
Double-blind Phase: 96 Weeks Duration Protocol Violation	18	16	0
Double-blind Phase: 96 Weeks Duration Met Protocol-defined Stopping Criteria	6	3	0
Double-blind Phase: 96 Weeks Duration Study Closed/Terminated	6	4	0
Double-blind Phase: 96 Weeks Duration Lost to Follow-up	22	10	0
Double-blind Phase: 96 Weeks Duration Withdrawal by Subject	18	14	0
Double-blind Phase: 96 Weeks Duration Physician Decision	3	0	0
Open-label Phase: Median of 1267 Days Adverse Event	0	0	4
Open-label Phase: Median of 1267 Days Lack of Efficacy	0	0	5
Open-label Phase: Median of 1267 Days Protocol Violation	0	0	5
Open-label Phase: Median of 1267 Days Met Protocol-defined Stopping Criteria	0	0	4
Open-label Phase: Median of 1267 Days Lost to Follow-up	0	0	15
Open-label Phase: Median of 1267 Days Withdrawal by Subject	0	0	8
Open-label Phase: Median of 1267 Days Physician Decision	0	0	3

Baseline Characteristics

A Trial Comparing GSK1349572 50mg Once Daily to Raltegravir 400mg Twice Daily

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DTG 50 mg Once a Day n=411 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF)/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID n=411 Participants Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.	Total n=822 Participants Total of all reporting groups
Age, Continuous	37.3 Years STANDARD_DEVIATION 9.19 • n=5 Participants	36.6 Years STANDARD_DEVIATION 10.02 • n=7 Participants	37.0 Years STANDARD_DEVIATION 9.61 • n=5 Participants
Sex: Female, Male Female	63 Participants n=5 Participants	56 Participants n=7 Participants	119 Participants n=5 Participants
Sex: Female, Male Male	348 Participants n=5 Participants	355 Participants n=7 Participants	703 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage (Her)	49 Participants n=5 Participants	39 Participants n=7 Participants	88 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized Central/South Asian Her	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Japanese/East Asian Her/South East Asian Her	4 Participants n=5 Participants	10 Participants n=7 Participants	14 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	346 Participants n=5 Participants	352 Participants n=7 Participants	698 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Her and Asian and White	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian and White	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 48

Population: ITT-E Population.

Outcome measures

Outcome measures
Measure	DTG 50 mg Once a Day n=411 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID n=411 Participants Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48	88 Percentage of participants	85 Percentage of participants

SECONDARY outcome

Timeframe: Week 48 and Week 96

Population: ITT-E Population

Number of participants with detectable virus that has genotypic or phenotypic evidence of Integrase Inhibitor (INI) resistance were assessed at Week 48 and Week 96. Integrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the deoxyribonucleic acid (DNA) of the host cell.

Outcome measures

Outcome measures
Measure	DTG 50 mg Once a Day n=411 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID n=411 Participants Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. Week 48, genotypic	0 Participants	1 Participants
Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. Week 48, phenotypic	1 Participants	2 Participants
Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. Week 96, genotypic	0 Participants	1 Participants
Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. Week 96, phenotypic	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Week 96

Population: ITT-E Population

The number of participants with plasma HIV-1 RNA level \<50 c/mL was assessed at Week 96.

Outcome measures

Outcome measures
Measure	DTG 50 mg Once a Day n=411 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID n=411 Participants Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Number of Participants With Plasma HIV-1 RNA <50 c/mL	332 Participants	314 Participants

SECONDARY outcome

Timeframe: Week 48 and Week 96

Population: ITT-E Population

The number of participants with plasma HIV-1 RNA level \<400 c/mL was assessed at Week 48 and Week 96.

Outcome measures

Outcome measures
Measure	DTG 50 mg Once a Day n=411 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID n=411 Participants Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Number of Participants With Plasma HIV-1 RNA <400 c/mL Week 48	369 Participants	356 Participants
Number of Participants With Plasma HIV-1 RNA <400 c/mL Week 96	338 Participants	321 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96

Population: ITT-E Population.

Change from Baseline in plasma HIV-1 RNA over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Baseline was defined as the measurements performed on Day 1. 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 (represented by n=x,x in the category titles).

Outcome measures

Outcome measures
Measure	DTG 50 mg Once a Day n=411 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID n=411 Participants Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Change From Baseline in Plasma HIV-1 RNA Over Time Baseline n=411, 411	4.538 log10 c/mL Standard Deviation 0.7258	4.599 log10 c/mL Standard Deviation 0.7048
Change From Baseline in Plasma HIV-1 RNA Over Time Week 4, n=402, 406	-2.817 log10 c/mL Standard Deviation 0.6198	-2.801 log10 c/mL Standard Deviation 0.6041
Change From Baseline in Plasma HIV-1 RNA Over Time Week 8, n=397, 402	-2.897 log10 c/mL Standard Deviation 0.6837	-2.886 log10 c/mL Standard Deviation 0.6754
Change From Baseline in Plasma HIV-1 RNA Over Time Week 12, n=396, 395	-2.908 log10 c/mL Standard Deviation 0.6863	-2.918 log10 c/mL Standard Deviation 0.6834
Change From Baseline in Plasma HIV-1 RNA Over Time Week 16, n=395, 388	-2.917 log10 c/mL Standard Deviation 0.6949	-2.943 log10 c/mL Standard Deviation 0.6841
Change From Baseline in Plasma HIV-1 RNA Over Time Week 24, n=393, 390	-2.896 log10 c/mL Standard Deviation 0.7889	-2.933 log10 c/mL Standard Deviation 0.7398
Change From Baseline in Plasma HIV-1 RNA Over Time Week 32, n=386, 377	-2.907 log10 c/mL Standard Deviation 0.7609	-2.947 log10 c/mL Standard Deviation 0.7613
Change From Baseline in Plasma HIV-1 RNA Over Time Week 40, n=375, 358	-2.920 log10 c/mL Standard Deviation 0.7219	-2.946 log10 c/mL Standard Deviation 0.6700
Change From Baseline in Plasma HIV-1 RNA Over Time Week 48, n=374, 358	-2.915 log10 c/mL Standard Deviation 0.7237	-2.942 log10 c/mL Standard Deviation 0.6737
Change From Baseline in Plasma HIV-1 RNA Over Time Week 60, n=366, 355	-2.912 log10 c/mL Standard Deviation 0.7344	-2.937 log10 c/mL Standard Deviation 0.6685
Change From Baseline in Plasma HIV-1 RNA Over Time Week 72, n=361, 350	-2.917 log10 c/mL Standard Deviation 0.7261	-2.932 log10 c/mL Standard Deviation 0.6728
Change From Baseline in Plasma HIV-1 RNA Over Time Week 84, n=352, 338	-2.932 log10 c/mL Standard Deviation 0.7073	-2.916 log10 c/mL Standard Deviation 0.6646
Change From Baseline in Plasma HIV-1 RNA Over Time Week 96, n=342, 329	-2.938 log10 c/mL Standard Deviation 0.7004	-2.901 log10 c/mL Standard Deviation 0.7072

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96

Population: ITT-E Population.

Absolute values in plasma HIV-1 RNA over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Only those participants with data 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 Once a Day n=411 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID n=411 Participants Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Absolute Values in Plasma HIV-1 RNA Over Time Baseline n=411, 411	4.538 log10 c/mL Standard Deviation 0.7258	4.599 log10 c/mL Standard Deviation 0.7048
Absolute Values in Plasma HIV-1 RNA Over Time Week 4, n=402, 406	1.718 log10 c/mL Standard Deviation 0.2593	1.800 log10 c/mL Standard Deviation 0.4095
Absolute Values in Plasma HIV-1 RNA Over Time Week 8, n=397, 402	1.646 log10 c/mL Standard Deviation 0.2006	1.709 log10 c/mL Standard Deviation 0.3791
Absolute Values in Plasma HIV-1 RNA Over Time Week 12, n=396, 395	1.626 log10 c/mL Standard Deviation 0.1323	1.672 log10 c/mL Standard Deviation 0.3125
Absolute Values in Plasma HIV-1 RNA Over Time Week 16, n=395, 388	1.620 log10 c/mL Standard Deviation 0.1252	1.648 log10 c/mL Standard Deviation 0.2647
Absolute Values in Plasma HIV-1 RNA Over Time Week 24, n=393, 390	1.643 log10 c/mL Standard Deviation 0.2950	1.655 log10 c/mL Standard Deviation 0.3476
Absolute Values in Plasma HIV-1 RNA Over Time Week 32, n=386, 377	1.620 log10 c/mL Standard Deviation 0.1917	1.636 log10 c/mL Standard Deviation 0.2721
Absolute Values in Plasma HIV-1 RNA Over Time Week 40, n=375, 358	1.603 log10 c/mL Standard Deviation 0.0821	1.601 log10 c/mL Standard Deviation 0.0784
Absolute Values in Plasma HIV-1 RNA Over Time Week 48, n=374, 358	1.606 log10 c/mL Standard Deviation 0.0866	1.599 log10 c/mL Standard Deviation 0.0582
Absolute Values in Plasma HIV-1 RNA Over Time Week 60, n=366, 355	1.605 log10 c/mL Standard Deviation 0.1134	1.599 log10 c/mL Standard Deviation 0.0560
Absolute Values in Plasma HIV-1 RNA Over Time Week 72, n=361, 350	1.601 log10 c/mL Standard Deviation 0.0803	1.605 log10 c/mL Standard Deviation 0.0836
Absolute Values in Plasma HIV-1 RNA Over Time Week 84, n=352, 338	1.607 log10 c/mL Standard Deviation 0.1337	1.614 log10 c/mL Standard Deviation 0.1279
Absolute Values in Plasma HIV-1 RNA Over Time Week 96, n=342, 329	1.599 log10 c/mL Standard Deviation 0.830	1.630 log10 c/mL Standard Deviation 0.2515

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96

Population: ITT-E Population.

CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immuno compromise. The CD4 count is used to stage the participants disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start ART. Changes from Baseline in CD4+ cell counts over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Baseline was defined as measurements performed on Day 1. 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 (represented by n=x,x in the category titles).

Outcome measures

Outcome measures
Measure	DTG 50 mg Once a Day n=411 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID n=411 Participants Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Baseline n=411, 411	379.2 Cells per cubic millimeter (cells/mm^3) Standard Deviation 178.32	374.3 Cells per cubic millimeter (cells/mm^3) Standard Deviation 163.37
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 4, n=398, 403	93.3 Cells per cubic millimeter (cells/mm^3) Standard Deviation 116.27	97.2 Cells per cubic millimeter (cells/mm^3) Standard Deviation 129.35
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 8, n=398, 402	121.6 Cells per cubic millimeter (cells/mm^3) Standard Deviation 127.97	126.6 Cells per cubic millimeter (cells/mm^3) Standard Deviation 134.59
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 12, n=392, 397	130.7 Cells per cubic millimeter (cells/mm^3) Standard Deviation 131.49	145.1 Cells per cubic millimeter (cells/mm^3) Standard Deviation 144.08
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 16, n=394, 392	155.1 Cells per cubic millimeter (cells/mm^3) Standard Deviation 137.23	173.0 Cells per cubic millimeter (cells/mm^3) Standard Deviation 159.10
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 24, n=392, 389	199.3 Cells per cubic millimeter (cells/mm^3) Standard Deviation 161.23	204.2 Cells per cubic millimeter (cells/mm^3) Standard Deviation 162.28
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 32, n=384, 375	223.4 Cells per cubic millimeter (cells/mm^3) Standard Deviation 165.30	241.3 Cells per cubic millimeter (cells/mm^3) Standard Deviation 167.64
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 40, n=371, 357	224.1 Cells per cubic millimeter (cells/mm^3) Standard Deviation 173.59	239.8 Cells per cubic millimeter (cells/mm^3) Standard Deviation 173.33
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 48, n=374, 357	238.9 Cells per cubic millimeter (cells/mm^3) Standard Deviation 171.81	257.5 Cells per cubic millimeter (cells/mm^3) Standard Deviation 178.69
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 60, n=367, 355	247.8 Cells per cubic millimeter (cells/mm^3) Standard Deviation 184.11	264.2 Cells per cubic millimeter (cells/mm^3) Standard Deviation 188.63
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 72, n=360, 350	247.8 Cells per cubic millimeter (cells/mm^3) Standard Deviation 168.37	278.6 Cells per cubic millimeter (cells/mm^3) Standard Deviation 182.76
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 84, n=351, 338	281.3 Cells per cubic millimeter (cells/mm^3) Standard Deviation 175.07	292.9 Cells per cubic millimeter (cells/mm^3) Standard Deviation 199.42
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time Week 96, n=343, 328	292.2 Cells per cubic millimeter (cells/mm^3) Standard Deviation 195.70	286.2 Cells per cubic millimeter (cells/mm^3) Standard Deviation 192.45

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96

Population: ITT-E Population.

CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immuno compromise. The CD4 count is used to stage the patient's disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start antiretroviral therapy absolute values in CD4+ cell counts over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Only those participants with data 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 Once a Day n=411 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID n=411 Participants Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Absolute Values in CD4+ Cell Counts Over Time Baseline n=411, 411	379.2 cells/mm^3 Standard Deviation 172.32	374.3 cells/mm^3 Standard Deviation 163.37
Absolute Values in CD4+ Cell Counts Over Time Week 4, n=398, 403	474.2 cells/mm^3 Standard Deviation 199.06	471.8 cells/mm^3 Standard Deviation 191.02
Absolute Values in CD4+ Cell Counts Over Time Week 8, n=398, 402	502.3 cells/mm^3 Standard Deviation 205.15	502.4 cells/mm^3 Standard Deviation 187.99
Absolute Values in CD4+ Cell Counts Over Time Week 12, n=392, 397	513.3 cells/mm^3 Standard Deviation 218.75	518.3 cells/mm^3 Standard Deviation 195.59
Absolute Values in CD4+ Cell Counts Over Time Week 16, n=394, 392	536.4 cells/mm^3 Standard Deviation 219.47	550.1 cells/mm^3 Standard Deviation 221.77
Absolute Values in CD4+ Cell Counts Over Time Week 24, n=392, 389	582.0 cells/mm^3 Standard Deviation 232.93	580.8 cells/mm^3 Standard Deviation 218.76
Absolute Values in CD4+ Cell Counts Over Time Week 32, n=384, 375	606.5 cells/mm^3 Standard Deviation 242.95	618.7 cells/mm^3 Standard Deviation 237.56
Absolute Values in CD4+ Cell Counts Over Time Week 40, n=371, 357	609.1 cells/mm^3 Standard Deviation 239.11	623.1 cells/mm^3 Standard Deviation 234.82
Absolute Values in CD4+ Cell Counts Over Time Week 48, n=374, 357	623.8 cells/mm^3 Standard Deviation 247.82	641.2 cells/mm^3 Standard Deviation 241.75
Absolute Values in CD4+ Cell Counts Over Time Week 60, n=367, 355	635.6 cells/mm^3 Standard Deviation 241.27	648.5 cells/mm^3 Standard Deviation 238.99
Absolute Values in CD4+ Cell Counts Over Time Week 72, n=360, 350	635.2 cells/mm^3 Standard Deviation 237.78	664.0 cells/mm^3 Standard Deviation 239.86
Absolute Values in CD4+ Cell Counts Over Time Week 84, n=351, 338	668.0 cells/mm^3 Standard Deviation 246.50	677.5 cells/mm^3 Standard Deviation 249.64
Absolute Values in CD4+ Cell Counts Over Time Week 96, n=343, 328	679.8 cells/mm^3 Standard Deviation 257.89	672.4 cells/mm^3 Standard Deviation 237.54

SECONDARY outcome

Timeframe: From Baseline until Week 96

Population: ITT-E Population

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: CDC CAT A at Baseline to a CDC CAT C event (EV); CDC CAT B at Baseline to a CDC CAT C EV; CDC CAT C at Baseline to a new CDC CAT C EV; or CDC CAT A, B, or C at Baseline to death.

Outcome measures

Outcome measures
Measure	DTG 50 mg Once a Day n=411 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID n=411 Participants Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences Any category condition	10 Participants	8 Participants
Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences Any Category B condition	3 Participants	3 Participants
Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences Any Category C condition	6 Participants	4 Participants
Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences Any death	1 Participants	1 Participants
Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences Progression from CAT A to CAT C	4 Participants	2 Participants
Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences Progression from CAT B to CAT C	3 Participants	1 Participants
Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences Progression from CAT C to new CAT C	0 Participants	1 Participants
Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences Progression from CAT A, B, or C to death	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From Baseline until Week 96

Population: Safety Population.

All Grade 1 to 4 post-Baseline-emergent chemistry toxicities included alanine aminotransferase (ALT), alkaline phosphatase (ALP), asparate aminotransferase (AST), carbon dioxide (CO2) content/bicarbonate, cholesterol, creatine kinase (CK), creatinine, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol calculation, lipase, phosphorus inorganic, total bilirubin, and triglycerides. All Grade 1 to 4 post-Baseline-emergent hematology toxities included hemoglobin, platelet count, total neutrophils, and white blood cell count. The Division of AIDS (DAIDS) defined toxicity grades as follows: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening; Grade 5, death. Safety Population: all participants who received at least one dose of investigational product

Outcome measures

Outcome measures
Measure	DTG 50 mg Once a Day n=411 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID n=411 Participants Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) ALT	57 Participants	70 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) ALP	7 Participants	15 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) AST	67 Participants	75 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) CO2 content/bicarbonate	58 Participants	67 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Cholesterol	90 Participants	73 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) CK	61 Participants	47 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Creatinine	11 Participants	7 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Hyperglycaemia	70 Participants	87 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Hyperkalemia	7 Participants	4 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Hypernatremia	4 Participants	6 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Hypoglycaemia	17 Participants	27 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Hypokalemia	10 Participants	15 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Hyponatremia	34 Participants	48 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) LDL cholesterol calculation	74 Participants	49 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Lipase	55 Participants	62 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Phosphorus, inorganic	65 Participants	71 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Total bilirubin	27 Participants	24 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Triglycerides	7 Participants	8 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Hemoglobin	10 Participants	5 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Platelet count	19 Participants	19 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) Total neutrophils	54 Participants	48 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) White Blood Cell count	19 Participants	7 Participants

SECONDARY outcome

Timeframe: Week 4, Week 24, and Week 48

Population: PK Concentration Population

AUC is defined as the area under the DTG concentration-time curve as a measure of drug exposure over time. AUC(0-tau) is defined as the area under the plasma concentration-time curve from time zero to time tau over a dosing interval at steady state, where tau is the length of the dosing interval of DTG. The predicted individual AUC(0-tau) were obtained from the final population PK model by an empirical Bayes estimation. Blood samples for PK assessments were collected at pre-dose (within 15 minutes prior to dose) at Week 4, Week 24, and Week 48 and 1 to 3 hours post-dose or 4 to 12 hours post-dose at Week 4 and Week 24. If 1 to 3 hours post-dose was completed at Week 4, then the 4 to12 hour post-dose must be obtained at Week 48, and vice versa. The Pharmacokinetic (PK) Concentration Population comprised of all participants who received DTG, had undergone PK sampling during the study, and provided evaluable DTG plasma concentration data.

Outcome measures

Outcome measures
Measure	DTG 50 mg Once a Day n=403 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau [AUC(0-tau)] of DTG	53.6 Microgramshour per milliliter(µghr/mL) Geometric Coefficient of Variation 26.8	—

SECONDARY outcome

Timeframe: Week 4, Week 24, and Week 48

Population: PK Concentration Population.

The maximum plasma concentration (Cmax) and concentration at the end of a dosing interval (Ctau) of DTG were assessed at Week 48. The predicted individual Cmax and Ctau were obtained from the final population PK model by simulation of the concentration-time profiles. Blood samples for PK assessments were collected at pre-dose (within 15 minutes prior to dose) at Week 4, Week 24, and Week 48 and 1 to 3 hours post-dose or 4 to 12 hours post-dose at Week 4 and Week 24. If 1 to 3 hour post-dose was completed at Week 4, then the 4 to12 hour post-dose must be obtained at Week 48, and vice versa.

Outcome measures

Outcome measures
Measure	DTG 50 mg Once a Day n=403 Participants Participants received DTG 50 mg once a day in combination with NRTI therapy, either with ABC/3TC or TDF/FTC. Participants were given the opportunity to receive DTG 50 mg once a day during an Open-label Phase of the study.	RTG 400 mg BID Participants received RTG 400 mg BID in combination with NRTI therapy, either with ABC/3TC or TDF/FTC.
Maximum Plasma Concentration (Cmax) and Concentration at the End of a Dosing Interval (Ctau) of DTG Cmax	3.69 Micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 19.6	—
Maximum Plasma Concentration (Cmax) and Concentration at the End of a Dosing Interval (Ctau) of DTG Ctau	1.10 Micrograms per milliliter (µg/mL) Geometric Coefficient of Variation 46.5	—

Adverse Events

DTG 50 mg Once a Day

Serious events: 41 serious events

Other events: 353 other events

Deaths: 1 deaths

RTG 400mg BID

Serious events: 45 serious events

Other events: 344 other events

Deaths: 1 deaths

DTG 50 mg Once a Day (Open-label)

Serious events: 21 serious events

Other events: 256 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