Trial Outcomes & Findings for A Trial Comparing GSK1349572 50mg Plus Abacavir/Lamivudine Once Daily to Atripla (Also Called The SINGLE Trial) (NCT NCT01263015)

Last Updated: 2018-04-04

Results Overview

The percentage of participants with plasma HIV-1 RNA \<50 c/mL at Week 48 was assessed. Plasma samples were collected for the quantitative assessment of HIV-1 RNA based on the Missing, Switch, or Discontinuation equals Failure (MSDF) algorithm,as codified by the Food and Drug Administration's Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigationl product prior to the visit window) as non-responders, as well as participants who switched their concomitant antiretroviral therapy (ART) in certain scenarios. Since changes in ART were not permitted in this protocol, all such participants who changed ART were to be considered non-responders. Otherwise, virologic success or failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the visit of interest window.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

844 participants

Primary outcome timeframe

Week 48

Results posted on

2018-04-04

Participant Flow

Study consisted of 96 weeks double-blind phase, followed by a 48 week open-label phase.

A total of 844 participants (par.) were randomized (1:1) to one of the two treatment arms. Of these, 833 par. received at least one dose of study medication. Of the 11 par. who were randomized but not treated with investigational product, 7 par. withdrew consent, 3 par. were randomized in error, and 1 par. was lost to follow-up.

Participant milestones

Participant milestones
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks.	EFV/TDF/FTC 600/200/300 mg Once Daily During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks.
Double-blind Phase: 96 Weeks Duration STARTED	414	419
Double-blind Phase: 96 Weeks Duration COMPLETED	342	310
Double-blind Phase: 96 Weeks Duration NOT COMPLETED	72	109
Open-label Phase: 48 Weeks Duration STARTED	341	309
Open-label Phase: 48 Weeks Duration COMPLETED	317	278
Open-label Phase: 48 Weeks Duration NOT COMPLETED	24	31

Reasons for withdrawal

Reasons for withdrawal
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks.	EFV/TDF/FTC 600/200/300 mg Once Daily During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks.
Double-blind Phase: 96 Weeks Duration Adverse Event	13	48
Double-blind Phase: 96 Weeks Duration Lack of Efficacy	18	14
Double-blind Phase: 96 Weeks Duration Protocol Violation	14	12
Double-blind Phase: 96 Weeks Duration Lost to Follow-up	17	18
Double-blind Phase: 96 Weeks Duration Withdrawal by Subject	9	15
Double-blind Phase: 96 Weeks Duration Physician Decision	1	2
Open-label Phase: 48 Weeks Duration Adverse Event	3	10
Open-label Phase: 48 Weeks Duration Lack of Efficacy	7	2
Open-label Phase: 48 Weeks Duration Protocol Violation	3	2
Open-label Phase: 48 Weeks Duration Lost to Follow-up	8	8
Open-label Phase: 48 Weeks Duration Physician Decision	0	2
Open-label Phase: 48 Weeks Duration Withdrawal by Subject	3	7

Baseline Characteristics

A Trial Comparing GSK1349572 50mg Plus Abacavir/Lamivudine Once Daily to Atripla (Also Called The SINGLE Trial)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=414 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=419 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.	Total n=833 Participants Total of all reporting groups
Age, Continuous	36.5 Years STANDARD_DEVIATION 10.74 • n=5 Participants	36.4 Years STANDARD_DEVIATION 10.43 • n=7 Participants	36.4 Years STANDARD_DEVIATION 10.58 • n=5 Participants
Sex: Female, Male Female	67 Participants n=5 Participants	63 Participants n=7 Participants	130 Participants n=5 Participants
Sex: Female, Male Male	347 Participants n=5 Participants	356 Participants n=7 Participants	703 Participants n=5 Participants
Race/Ethnicity, Customized African American (Af Am)/African Heritage (Af Ht)	98 participants n=5 Participants	99 participants n=7 Participants	197 participants n=5 Participants
Race/Ethnicity, Customized American Indian (AI) or Alaska Native (Nat)	13 participants n=5 Participants	17 participants n=7 Participants	30 participants n=5 Participants
Race/Ethnicity, Customized Asian	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants
Race/Ethnicity, Customized White	284 participants n=5 Participants	285 participants n=7 Participants	569 participants n=5 Participants
Race/Ethnicity, Customized Af Am/Af Ht & AI or Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Af Am/Af Ht & Nat Hawaiian/other Pacific Islander	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Af Am/Af Ht & White	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native & White	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Race/Ethnicity, Customized Asian & White	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Missing	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: Intent-to-Treat-Exposed (ITT-E) Population: all randomized participants who received at least one dose of study medication

Outcome measures

Outcome measures
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=414 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=419 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
Proportion of Subjects Responding Based on Plasma HIV-1 RNA <50 c/mL at Week 48	88 Percentage of participants	81 Percentage of participants

SECONDARY outcome

Timeframe: From Baseline until Week 144) (average of 877.4 days for DTG; average of 788.8 study days for EFV/TDF/FTC)

Population: ITT-E Population

Viral suppression is defined as the first viral load value\<50 c/mL. The Kaplan-Meier method was used to estimate time to viral suppression, defined as the time from the first dose of study treatment until the first viral load value \<50 c/mL was reached. Participants who withdrew for any reason without having suppressed prior to the analysis were censored.

Outcome measures

Outcome measures
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=414 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=419 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
Time to Viral Suppression (<50 c/mL)	28 Days Interval 28.0 to 29.0	84 Days Interval 83.0 to 84.0

SECONDARY outcome

Timeframe: Week 96 and Week 144

Population: Intent-to-Treat-Exposed (ITT-E) Population: all randomized participants who received at least one dose of study medication

The percentage of participants with plasma HIV-1 RNA \<50 c/mL at Week 96 and Week 144 was assessed. Plasma samples were collected for the quantitative assessment of HIV-1 RNA based on the Missing, Switch, or Discontinuation equals Failure (MSDF) algorithm,as codified by the Food and Drug Administration's Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigationl product prior to the visit window) as non-responders, as well as participants who switched their concomitant antiretroviral therapy (ART) in certain scenarios. Since changes in ART were not permitted in this protocol, all such participants who changed ART were to be considered non-responders. Otherwise, virologic success or failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the visit of interest window.

Outcome measures

Outcome measures
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=414 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=419 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 96 and Week 144 Week 144	71 Percentage of participants	63 Percentage of participants
Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 96 and Week 144 Week 96	77 Percentage of participants	70 Percentage of participants

SECONDARY outcome

Timeframe: From Baseline until Week 144) (average of 877.4 days for DTG; average of 788.8 study days for EFV/TDF/FTC)

Population: ITT-E Population

Data are presented as Kaplan Meier estimates of virologic failure (VF), defined as a confirmed plasma HIV-1 RNA level \>=1000 c/mL at or after Week 16 and before Week 24, or a confirmed plasma HIV-1 RNA level \>=200 c/mL at or after Week 24. A plasma HIV-1 RNA value was considered to be confirmed failure if a consecutive measurement satisfied the same failure criterion. The number of participants who experienced autoimmune deficiency syndrome (AIDS) Clinical Trials Group (ACTG) VFs was measured. For participants who withdrew from the study/were not documented to have reached confirmed VF at the cut off date of the Week 48 analysis, time to VF was to be censored at the planned visit week of the last measured plasma HIV-1 RNA sample. Data for participants who missed three consecutive scheduled plasma HIV-1 RNA measurements were to be censored at the planned visit week of the last assessment prior to the 3 consecutive missed visits.

Outcome measures

Outcome measures
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=414 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=419 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
Number of Participants With a Confirmed Plasma HIV-1 RNA Level >=1000 c/mL at or After Week 16 and Before Week 24, or a Confirmed Plasma HIV-1 RNA Level >=200 c/mL at or After Week 24 ACTG virologic failures	11 Participants 0.58	8 Participants 0.52
Number of Participants With a Confirmed Plasma HIV-1 RNA Level >=1000 c/mL at or After Week 16 and Before Week 24, or a Confirmed Plasma HIV-1 RNA Level >=200 c/mL at or After Week 24 Censored participants	403 Participants 0.70	411 Participants 0.63

SECONDARY outcome

Timeframe: Baseline and at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144

Population: ITT-E Population

Blood samples were collected for the measurement of HIV-1 RNA in plasma. Changes from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants available at the indicated time points were assessed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=414 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=419 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 2, n=387, 376	-2.46 log10 copies/mL Standard Deviation 0.49	-1.96 log10 copies/mL Standard Deviation 0.46
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 4, n=404, 391	-2.88 log10 copies/mL Standard Deviation 0.58	-2.25 log10 copies/mL Standard Deviation 0.52
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 8, n=395, 386	-2.99 log10 copies/mL Standard Deviation 0.64	-2.60 log10 copies/mL Standard Deviation 0.60
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 12, n=394, 377	-3.01 log10 copies/mL Standard Deviation 0.70	-2.85 log10 copies/mL Standard Deviation 0.63
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 16, n=386, 366	-3.03 log10 copies/mL Standard Deviation 0.66	-2.98 log10 copies/mL Standard Deviation 0.65
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 24, n=389, 364	-3.05 log10 copies/mL Standard Deviation 0.69	-3.01 log10 copies/mL Standard Deviation 0.76
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 32, n=380, 355	-3.04 log10 copies/mL Standard Deviation 0.70	-3.05 log10 copies/mL Standard Deviation 0.72
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 40, n=370, 345	-3.05 log10 copies/mL Standard Deviation 0.68	-3.04 log10 copies/mL Standard Deviation 0.70
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 48, n=370, 343	-3.03 log10 copies/mL Standard Deviation 0.69	-3.04 log10 copies/mL Standard Deviation 0.69
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 60, n=360, 330	-3.03 log10 copies/mL Standard Deviation 0.67	-3.05 log10 copies/mL Standard Deviation 0.69
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 72, n=354, 320	-3.03 log10 copies/mL Standard Deviation 0.70	-3.06 log10 copies/mL Standard Deviation 0.70
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 84, n=353, 314	-3.02 log10 copies/mL Standard Deviation 0.70	-3.07 log10 copies/mL Standard Deviation 0.68
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 96, n=345, 310	-2.99 log10 copies/mL Standard Deviation 0.73	-3.06 log10 copies/mL Standard Deviation 0.68
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 108, n=340, 300	-3.01 log10 copies/mL Standard Deviation 0.71	-3.08 log10 copies/mL Standard Deviation 0.67
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 120, n=333, 289	-3.00 log10 copies/mL Standard Deviation 0.77	-3.07 log10 copies/mL Standard Deviation 0.67
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 132, n=323, 284	-3.03 log10 copies/mL Standard Deviation 0.68	-3.06 log10 copies/mL Standard Deviation 0.67
Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 144, n=313,269	-3.02 log10 copies/mL Standard Deviation 0.72	-3.04 log10 copies/mL Standard Deviation 0.69

SECONDARY outcome

Timeframe: Baseline and Week 144

Population: ITT-E Population

Cluster of differentiation (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 immunocompromise. 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. Change from Baseline was calculated as the Week 144 value minus the Baseline value. The least squares mean is the estimated mean change from Baseline in CD4+ cell counts at Week 144 calculated from a repeated measures model including the following covariates: treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, treatment\*visit interaction, Baseline HIV-1 RNA\*visit interaction, and Baseline CD4+ cell count\*visit interaction. No assumptions were made about the correlations between a participant's readings of CD4+, i.e., the correlation matrix for within-participant errors is unstructured.

Outcome measures

Outcome measures
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=414 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=419 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
Change From Baseline in CD4+ Cell Counts at Week 144	378.48 cells per millimeters cubed (cells/mm^3) Standard Deviation 10.99	331.57 cells per millimeters cubed (cells/mm^3) Standard Deviation 11.59

SECONDARY outcome

Timeframe: Baseline and Week 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144

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 immunocompromise. 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. Change from Baseline was calculated as the value at Indicated visit minus the Baseline value. Only those participants available at the indicated time points were assessed (represented by n=X, X in the category titles).

Outcome measures

SECONDARY outcome

Timeframe: From Baseline until Week 144

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

Outcome measures

Outcome measures
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=414 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=419 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences at Week 144 Week 144, Any category condition	17 Participants	24 Participants
Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences at Week 144 Week 144, Any Category B condition	12 Participants	17 Participants
Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences at Week 144 Week 144, Any Category C condition	5 Participants	6 Participants
Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences at Week 144 Week 144, Any death	0 Participants	2 Participants
Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences at Week 144 Week 144, Progression from CAT A to CAT C	4 Participants	4 Participants
Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences at Week 144 Week 144, Progression from CAT C to new CAT C	1 Participants	2 Participants
Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences at Week 144 Week 144, Progression from CAT A, B, or C to death	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From Baseline until Week 144

Population: Safety Population: all participants who received at least one dose of investigational product

All Grade 1 to 4 post-Baseline-emergent chemistry toxicities included alanine aminotransferase (ALT), albumin, 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.

Outcome measures

Outcome measures
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=414 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=419 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Albumin	0 Participants	1 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, ALT	62 Participants 0.3849	81 Participants 0.3854
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, ALP	17 Participants	53 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, AST	77 Participants	85 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, CO2 content/bicarbonate	135 Participants	134 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Cholesterol	156 Participants	140 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, CK	91 Participants	79 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Creatinine	17 Participants	6 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Hyperglycaemia	121 Participants	105 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Hyperkalemia	4 Participants	12 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Hypernatremia	11 Participants	9 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Hypoglycaemia	24 Participants	21 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Hypokalemia	38 Participants	21 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Hyponatremia	63 Participants	86 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, LDL cholesterol calculation	124 Participants	111 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Lipase	111 Participants	110 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Phosphorus, inorganic	109 Participants	134 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Total bilirubin	22 Participants	4 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Triglycerides	11 Participants	11 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Hemoglobin	7 Participants	11 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Platelet count	20 Participants	19 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, Total neutrophils	70 Participants	80 Participants
Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144 Week 144, White Blood Cell count	9 Participants	18 Participants

SECONDARY outcome

Timeframe: Through Week 144

Population: PDVF Genotypic Population: all participants in the ITT-E Population with available on-treatment genotypic resistance data at the time of PDVF

Whole blood samples were collected from participants to provide plasma for storage samples for potential viral genotypic and phenotypic analyses. Participants with confirmed virological failure (confirmed HIV-1 RNA \>=50 copies/mL throughout the study and/or confirmed HIV-1 RNA \>=200 copies/mL at Week 144) had plasma samples tested for HIV-1 RT genotype and HIV-1 integrase genotype from Baseline samples and from samples collected at the time of virological failure. Genotype testing was conducted at Day 1 and at the time of suspected protocol-defined virological failure (PDVF). A genotyping assessment was made of change across all amino acids within the integrase (IN)-encoding region, with particular attention paid to specific amino acid changes associated with the development of resistance to RAL, ELV, or DTG.

Outcome measures

Outcome measures
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=26 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=16 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF) Through 144 Week 144, RT mutation K65K/R	0 Participants	1 Participants
Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF) Through 144 Week 144, RT mutation K101E	0 Participants	1 Participants
Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF) Through 144 Week 144, RT mutation K103K/N	0 Participants	2 Participants
Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF) Through 144 Week 144, RT mutation K103N	0 Participants	2 Participants
Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF) Through 144 Week 144, RT mutation G190G/A	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and Week 4 through 48

Population: ITT-E Population. Participants with missing bother item scores at Week 4 had their last observation carried forward (LOCF). Only those participants contributing to the model (i.e., without missing response variables after LOCF or covariates) were analyzed.

The Symptom Distress Module (SDM) is a 20-item, self-reported questionnaire measuring the presence/perceived distress linked to symptoms associated with HIV/its treatments. Developed with support from the AIDS Clinical Trials Group of the U.S. National Institute of Allergy and Infectious Diseases, it has demonstrated construct validity and has shown strong associations with physical/mental health summary scores and with disease severity. The SDM consists of 2 main scores: symptom count and the SBS, ranging from 0 (best) to 80 (worst) and based on the degree of bother that each symptom present posed. The SBS was calculated by adding the 20 individual bother item scores, which were calculated as: 0, "I do not have this symptom"; 1, "It doesn't bother me"; 2, "It bothers me a little"; 3, "It bothers me"; 4, "It bothers me a lot." Estimates are calculated from an analysis of covariance (ANCOVA) model adjusting for age, sex, race, Baseline (BL) viral load, BL CD4+ cell count, and BL SBS.

Outcome measures

Outcome measures
Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=394 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=393 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
Change From Baseline in the Symptom Bother Score (SBS) at Week 4 Through Week 48	-1.818 Scores on a scale Standard Error 0.3849	-1.246 Scores on a scale Standard Error 0.3854

Adverse Events

DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily

Serious events: 65 serious events

Other events: 332 other events

Deaths: 0 deaths

EFV/TDF/FTC 600/200/300 mg Once Daily

Serious events: 60 serious events

Other events: 358 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

Measure	DTG 50 mg Plus ABC/3TC 600/300 mg Once Daily n=414 Participants During double-blind phase, participants received a dolutegravir (DTG) 50 milligram (mg) tablet along with an Abacavir/Lamivudine (ABC/3TC) 600/300 mg tablet once daily (OD) orally, with placebo to match Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine (EFV/TDF/FTC) 600/200/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive DTG 50 mg tablet along with ABC/3TC 600/300 mg tablet OD orally, for additional 48 weeks during open-label phase.	EFV/TDF/FTC 600/200/300 mg Once Daily n=419 Participants During double-blind phase, participants received EFV/TDF/FTC 600/200/300 mg OD, with placebo to match DTG 50 mg and ABC/3TC 600/300 mg for 96 weeks. Participants who completed double-blind phase continued to receive EFV/TDF/FTC 600/200/300 mg OD for additional 48 weeks during open-label phase.
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 40, n=364,347	265.5 cells per millimeters cubed (cells/mm^3) Standard Deviation 187.81	216.2 cells per millimeters cubed (cells/mm^3) Standard Deviation 158.49
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 32, n=380,353	250.5 cells per millimeters cubed (cells/mm^3) Standard Deviation 172.06	208.1 cells per millimeters cubed (cells/mm^3) Standard Deviation 152.13
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 12, n=394,378	187.5 cells per millimeters cubed (cells/mm^3) Standard Deviation 157.46	153.0 cells per millimeters cubed (cells/mm^3) Standard Deviation 131.91
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 16, n=386,366	214.7 cells per millimeters cubed (cells/mm^3) Standard Deviation 173.35	174.1 cells per millimeters cubed (cells/mm^3) Standard Deviation 132.02
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 24, n=388,361	216.9 cells per millimeters cubed (cells/mm^3) Standard Deviation 162.89	177.8 cells per millimeters cubed (cells/mm^3) Standard Deviation 147.72
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 4, n=404,390	117.6 cells per millimeters cubed (cells/mm^3) Standard Deviation 114.51	80.9 cells per millimeters cubed (cells/mm^3) Standard Deviation 112.43
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 8, n=396,382	164.6 cells per millimeters cubed (cells/mm^3) Standard Deviation 129.98	124.4 cells per millimeters cubed (cells/mm^3) Standard Deviation 124.50
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 48, n=368,344	267.5 cells per millimeters cubed (cells/mm^3) Standard Deviation 192.30	209.5 cells per millimeters cubed (cells/mm^3) Standard Deviation 164.37
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 60, n=359,330	271.3 cells per millimeters cubed (cells/mm^3) Standard Deviation 188.05	235.3 cells per millimeters cubed (cells/mm^3) Standard Deviation 171.98
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 72, n=354,319	306.1 cells per millimeters cubed (cells/mm^3) Standard Deviation 202.02	269.6 cells per millimeters cubed (cells/mm^3) Standard Deviation 180.04
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 84, n=352,314	315.2 cells per millimeters cubed (cells/mm^3) Standard Deviation 197.92	272.1 cells per millimeters cubed (cells/mm^3) Standard Deviation 172.28
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 96, n=343,309	322.6 cells per millimeters cubed (cells/mm^3) Standard Deviation 205.35	286.0 cells per millimeters cubed (cells/mm^3) Standard Deviation 195.70
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 108, n=339,300	349.3 cells per millimeters cubed (cells/mm^3) Standard Deviation 218.76	298.9 cells per millimeters cubed (cells/mm^3) Standard Deviation 188.41
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 120, n=332,287	347.0 cells per millimeters cubed (cells/mm^3) Standard Deviation 234.96	311.0 cells per millimeters cubed (cells/mm^3) Standard Deviation 198.79
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 132, n=323,283	377.9 cells per millimeters cubed (cells/mm^3) Standard Deviation 205.78	327.2 cells per millimeters cubed (cells/mm^3) Standard Deviation 175.31
Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144 Week 144, n=313,270	379.5 cells per millimeters cubed (cells/mm^3) Standard Deviation 221.17	333.3 cells per millimeters cubed (cells/mm^3) Standard Deviation 189.25