Trial Outcomes & Findings for A Clinical Trial of GSK3640254 + Dolutegravir (DTG) in Human Immunodeficiency Virus-1 Infected Treatment-naive Adults (NCT NCT04900038)

Last Updated: 2023-12-14

Results Overview

Percentage of participants with plasma HIV-1 RNA \<50 c/mL at Week 24 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to evaluate the antiviral activity in HIV-1 infected ART (anti-retroviral therapy)-naïve participants.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

85 participants

Primary outcome timeframe

At Week 24

Results posted on

2023-12-14

Participant Flow

This study assessed efficacy, safety and resistance of GSK3640254 in combination with dolutegravir compared to dolutegravir + lamivudine in HIV-1 infected, treatment-naïve adults. The study was terminated by the sponsor after primary analysis (at week 24) as the sponsor determined further development of GSK3640254-containing daily oral regimen would not be differentiated enough from existing 2-drug daily oral regimens. Thus, secondary analyses at week 48 were not evaluated.

The changes from the planned subsequent analyses were presented as pre-specified in Statistical Analysis Plan. Safety analysis is presented based on the Entire Duration of Treatment Exposure period, which is defined from Day 1 up to end of continued access to treatment post-study termination (Day 478).

Participant milestones

Participant milestones
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC. Each participant received one capsule per day of each intervention up to Week 24.
Overall Study STARTED	22	20	22	21
Overall Study COMPLETED	2	3	2	3
Overall Study NOT COMPLETED	20	17	20	18

Reasons for withdrawal

Reasons for withdrawal
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC. Each participant received one capsule per day of each intervention up to Week 24.
Overall Study Adverse Event	1	0	1	1
Overall Study Withdrawal by Subject	0	1	0	0
Overall Study Study terminated by sponsor	18	15	17	14
Overall Study Protocol Deviation	1	1	0	0
Overall Study Participant reached protocol-defined stoping criteria	0	0	2	2
Overall Study Lost to Follow-up	0	0	0	1

Baseline Characteristics

A Clinical Trial of GSK3640254 + Dolutegravir (DTG) in Human Immunodeficiency Virus-1 Infected Treatment-naive Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=22 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=21 Participants Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC. Each participant received one capsule per day of each intervention up to Week 24.	Total n=85 Participants Total of all reporting groups
Age, Continuous	34.2 Years STANDARD_DEVIATION 7.53 • n=5 Participants	36.9 Years STANDARD_DEVIATION 10.51 • n=7 Participants	32.6 Years STANDARD_DEVIATION 8.41 • n=5 Participants	32.1 Years STANDARD_DEVIATION 8.62 • n=4 Participants	33.9 Years STANDARD_DEVIATION 8.83 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	15 Participants n=21 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	16 Participants n=7 Participants	17 Participants n=5 Participants	18 Participants n=4 Participants	70 Participants n=21 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	13 Participants n=21 Participants
Race/Ethnicity, Customized White	18 Participants n=5 Participants	14 Participants n=7 Participants	16 Participants n=5 Participants	14 Participants n=4 Participants	62 Participants n=21 Participants
Race/Ethnicity, Customized Mixed Race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Other - Unspecified	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	7 Participants n=21 Participants

PRIMARY outcome

Timeframe: At Week 24

Population: Analysis was performed on Intent-to-Treat Exposed (ITT-E) Population included all randomized participants who received at least one dose of study intervention and had data for plasma HIV-1 RNA \<50 c/mL as per timeline assessed.

Outcome measures

Outcome measures
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=22 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=21 Participants Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC.Each participant received one capsule per day of each intervention up to Week 24.
Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24	95 Percentage of participants	85 Percentage of participants	77 Percentage of participants	86 Percentage of participants

SECONDARY outcome

Timeframe: At Baseline (Day 1) and Week 24

Population: Analysis was performed on ITT-E Population that had data for absolute values of HIV-1 RNA as per timeline assessed.

Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log 10) values for plasma HIV-1 RNA has been presented. Baseline is defined as the latest non-missing value prior to first dose of treatment according to date and time including unscheduled visits.

Outcome measures

Outcome measures
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=22 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=21 Participants Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC.Each participant received one capsule per day of each intervention up to Week 24.
Absolute Values of HIV-1 RNA Through Week 24 Baseline (Day 1)	4.614 log10 copies per milliliter(log10 c/mL) Standard Deviation 0.5253	4.446 log10 copies per milliliter(log10 c/mL) Standard Deviation 0.5913	4.535 log10 copies per milliliter(log10 c/mL) Standard Deviation 0.4165	4.179 log10 copies per milliliter(log10 c/mL) Standard Deviation 0.5907
Absolute Values of HIV-1 RNA Through Week 24 Week 24	1.315 log10 copies per milliliter(log10 c/mL) Standard Deviation 0.0737	1.532 log10 copies per milliliter(log10 c/mL) Standard Deviation 0.7086	1.349 log10 copies per milliliter(log10 c/mL) Standard Deviation 0.1431	1.379 log10 copies per milliliter(log10 c/mL) Standard Deviation 0.2439

SECONDARY outcome

Timeframe: At Week 24 compared to baseline (Day 1)

Population: Analysis was performed on ITT-E Population that had data for absolute values of HIV-1 RNA as per timeline assessed.

Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log 10) values for plasma HIV-1 RNA has been presented. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=19 Participants Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC.Each participant received one capsule per day of each intervention up to Week 24.
Change From Baseline in HIV-1 RNA Through Week 24	-3.306 log10 c/mL Standard Deviation 0.5163	-2.874 log10 c/mL Standard Deviation 0.8476	-3.186 log10 c/mL Standard Deviation 0.4809	-2.767 log10 c/mL Standard Deviation 0.5531

SECONDARY outcome

Timeframe: At Baseline (Day 1) and Week 24

Population: Analysis was performed on ITT-E Population that had data for CD4+ T-cells analysis as per timeline assessed.

Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunologic activity. Baseline is defined as the latest non-missing value prior to first dose of treatment according to date and time including unscheduled visits.

Outcome measures

Outcome measures
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=22 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=21 Participants Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC.Each participant received one capsule per day of each intervention up to Week 24.
Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24 Baseline (Day 1)	436.7 cells per cubic millimeter (cells/mm^3) Standard Deviation 161.93	451.4 cells per cubic millimeter (cells/mm^3) Standard Deviation 164.86	534.8 cells per cubic millimeter (cells/mm^3) Standard Deviation 200.99	506.9 cells per cubic millimeter (cells/mm^3) Standard Deviation 165.14
Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24 Week 24	753.4 cells per cubic millimeter (cells/mm^3) Standard Deviation 222.73	661.0 cells per cubic millimeter (cells/mm^3) Standard Deviation 193.50	756.1 cells per cubic millimeter (cells/mm^3) Standard Deviation 267.69	627.5 cells per cubic millimeter (cells/mm^3) Standard Deviation 175.94

SECONDARY outcome

Timeframe: At Week 24 compared to baseline (Day 1)

Population: Analysis was performed on ITT-E Population that had data for CD4+ T-cells analysis as per timeline assessed.

Blood samples were collected and CD4+ cell count assessment was carried out to evaluate the immunologic activity. Change from Baseline is defined as post-dose visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=21 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=19 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=19 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=19 Participants Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC.Each participant received one capsule per day of each intervention up to Week 24.
Change From Baseline in CD4+ T-cell Counts Through Week 24	317.7 cells/mm^3 Standard Deviation 175.42	200.6 cells/mm^3 Standard Deviation 126.68	241.2 cells/mm^3 Standard Deviation 168.83	139.5 cells/mm^3 Standard Deviation 126.63

SECONDARY outcome

Timeframe: From Day 1 up to end of continued access to treatment post-study termination (Day 478)

Population: Analysis performed on Safety population, that included all randomized participants who took at least 1 dose of study intervention.

An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect. The study was terminated by the sponsor after primary analysis (at week 24). Adverse event data were collected up to end of continued access to treatment post-study termination (Day 478).

Outcome measures

Outcome measures
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=22 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=21 Participants Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC.Each participant received one capsule per day of each intervention up to Week 24.
Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478) SAEs	2 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478) Death	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 1 up to end of continued access to treatment post-study termination (Day 478)

Population: Analysis performed on Safety population, that included all randomized participants who took at least 1 dose of study intervention.

Number of participants who discontinued treatment due to AEs are presented. The study was terminated by the sponsor after primary analysis (at week 24). Adverse event data were collected up to end of continued access to treatment post-study termination (Day 478).

Outcome measures

Outcome measures
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=22 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=21 Participants Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC.Each participant received one capsule per day of each intervention up to Week 24.
Number of Participants With Adverse Events (AEs) Leading to Discontinuation, up to End of Continued Access to Treatment Post-study Termination (Day 478)	1 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 1 up to end of continued access to treatment post-study termination (Day 478)

Population: Analysis performed on Safety population, that included all randomized participants who took at least 1 dose of study intervention.

AEs of special interest (AESIs) included AEs related to QT prolongation, gastrointestinal (GI) intolerability/toxicity, psychiatric events, nervous system disorders, skin and subcutaneous tissue disorders and cardiac disorders. The study was terminated by the sponsor after primary analysis (at week 24). Adverse event data were collected up to end of continued access to treatment post-study termination (Day 478).

Outcome measures

Outcome measures
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=22 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=21 Participants Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC.Each participant received one capsule per day of each intervention up to Week 24.
Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) AEs related to QT prolongation	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) AEs related to GI intolerability/toxicity	5 Participants	7 Participants	8 Participants	5 Participants
Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) AEs related to psychiatric events	0 Participants	3 Participants	0 Participants	4 Participants
Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) AEs related to nervous system disorders	2 Participants	4 Participants	5 Participants	2 Participants
Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) AEs related to skin and subcutaneous tissue disorder	4 Participants	0 Participants	4 Participants	0 Participants
Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478) AEs related to cardiac disorders	1 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 1 up to Week 24

Population: Analysis was performed on ITT-E population.

Blood samples were collected for drug resistance testing to assess the development of viral resistance to GSK3640254 through Week 24. New mutations were tabulated by drug class: integrase strand transfer inhibitor (INSTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI). Protocol-Defined Virologic Failure (PDVF) was defined as having virologic non-response (HIV-1 RNA \<1.0 log10 c/mL reduction from baseline and \<200 copies/mL by Week 12, confirmed levels \>=200 c/mL at or after Week 24 and plasma HIV-1 RNA \<= 50 c/mL from testing on Week 24, virologic rebound (confirmed HIV-1 RNA \>=200 copies/mL after confirmed consecutive HIV-1 RNA \<50 copies/mL).

Outcome measures

Outcome measures
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=22 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=21 Participants Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC.Each participant received one capsule per day of each intervention up to Week 24.
Number of Participants Who Develop Genotypic Resistance up to Week 24	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 1 up to Week 24

Population: Analysis was performed on ITT-E Population.

Blood samples were collected for drug resistance testing to assess the development of viral resistance to GSK3640254 and other on-study Anti-Retroviral Therapy (ART) in participants experiencing virologic failure through Week 24. Only plasma HIV-1 RNA values determined by the central laboratory were used to assess virologic failure. PDVF was defined as having virologic non-response (HIV-1 RNA \<1.0 log10 c/mL reduction from baseline and \<200 copies/mL by Week 12, confirmed levels \>=200 c/mL at or after Week 24 and plasma HIV-1 RNA \<= 50 c/mL from testing on Week 24, virologic rebound (confirmed HIV-1 RNA \>=200 copies/mL after confirmed consecutive HIV-1 RNA \<50 copies/mL).

Outcome measures

Outcome measures
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=22 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=21 Participants Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC.Each participant received one capsule per day of each intervention up to Week 24.
Number of Participants Who Develop Phenotypic Resistance up to Week 24	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At Weeks 2, 4, 8, 12 (PRE DOSE), 12 (2-6HR POST DOSE), 24 (PRE DOSE), 24 (2-6HR POST DOSE)

Population: Analysis performed on Pharmacokinetic population, which included all participants who received GSK3640254, underwent sparse PK sampling during the study, and provided evaluable GSK3640254 plasma concentration data, demographic and baseline characteristics, and/or information on concomitant medications. Only those participants with data available at specified time points were analyzed for the specific category titles.

Trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered. This was determined to assess the steady-state exposure of GSK3640254 when given in combination with DTG.

Outcome measures

Outcome measures
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 Participants Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 Participants Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=22 Participants Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC.Each participant received one capsule per day of each intervention up to Week 24.
Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 Week 2	340.2 nanogram per milliliter (ng/mL) Interval 269.5 to 411.0	549.9 nanogram per milliliter (ng/mL) Interval 390.9 to 708.9	724.2 nanogram per milliliter (ng/mL) Interval 563.4 to 885.0	—
Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 Week 4	417.8 nanogram per milliliter (ng/mL) Interval 330.5 to 505.0	632.7 nanogram per milliliter (ng/mL) Interval 470.4 to 795.0	799.6 nanogram per milliliter (ng/mL) Interval 640.9 to 958.3	—
Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 Week 8	386.2 nanogram per milliliter (ng/mL) Interval 293.7 to 478.6	646.6 nanogram per milliliter (ng/mL) Interval 421.7 to 871.5	821.1 nanogram per milliliter (ng/mL) Interval 620.2 to 1022.0	—
Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 Week 12 ( PRE DOSE)	481.3 nanogram per milliliter (ng/mL) Interval 388.6 to 574.0	611.4 nanogram per milliliter (ng/mL) Interval 430.6 to 792.1	877.2 nanogram per milliliter (ng/mL) Interval 704.1 to 1050.3	—
Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 Week 12 (2-6HR POST DOSE)	767.8 nanogram per milliliter (ng/mL) Interval 612.3 to 923.3	1081.2 nanogram per milliliter (ng/mL) Interval 759.5 to 1402.8	1658.1 nanogram per milliliter (ng/mL) Interval 1305.8 to 2010.4	—
Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 Week 24 ( PRE DOSE)	396.0 nanogram per milliliter (ng/mL) Interval 331.0 to 460.8	570.1 nanogram per milliliter (ng/mL) Interval 333.6 to 806.6	848.8 nanogram per milliliter (ng/mL) Interval 600.3 to 1097.4	—
Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24 Week 24 (2-6HR POST DOSE)	759.0 nanogram per milliliter (ng/mL) Interval 623.1 to 894.8	1107.0 nanogram per milliliter (ng/mL) Interval 660.8 to 1553.2	1584.1 nanogram per milliliter (ng/mL) Interval 1067.3 to 2100.9	—

Adverse Events

GSK3640254 100 mg + Dolutegravir (DTG) 50 mg

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

GSK3640254 150 mg + DTG 50 mg

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

GSK3640254 200 mg + DTG 50 mg

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

DTG 50 mg + Lamivudine (3TC) 300 mg

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GSK3640254 100 mg + Dolutegravir (DTG) 50 mg n=22 participants at risk Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 150 mg + DTG 50 mg n=20 participants at risk Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	GSK3640254 200 mg + DTG 50 mg n=22 participants at risk Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.	DTG 50 mg + Lamivudine (3TC) 300 mg n=21 participants at risk Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC. Each participant received one capsule per day of each intervention up to Week 24.
Gastrointestinal disorders Anogenital dysplasia	0.00% 0/22 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).	0.00% 0/20 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).	0.00% 0/22 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).	4.8% 1/21 • Number of events 1 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).
General disorders Non-cardiac chest pain	4.5% 1/22 • Number of events 1 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).	0.00% 0/20 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).	0.00% 0/22 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).	0.00% 0/21 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).
Nervous system disorders Guillain-Barre syndrome	4.5% 1/22 • Number of events 1 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).	0.00% 0/20 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).	0.00% 0/22 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).	0.00% 0/21 • All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to end of continued access to treatment post-study termination (Day 478). The study was terminated by the sponsor after primary analysis (at week 24). As prespecified in Statistical analysis plan, AEs were collected up to end of continued access to treatment post-study termination (Day 478).

Other adverse events

Additional Information

GSK Response Center

ViiV Healthcare

Phone: 866-435-7343

Email: [email protected]

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