Trial Outcomes & Findings for Standard Versus Double Dose Dolutegravir in Patients With HIV-associated Tuberculosis (NCT NCT03851588)

NCT ID: NCT03851588

Last Updated: 2024-07-18

Results Overview

Proportion with HIV viral load \<50 copies/mL at 24 weeks analysed by modified intention to treat (ITT), which includes all participants who received at least one dose of dolutegravir, and according to the FDA snapshot algorithm.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 108 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2024-07-18

Participant Flow

Participant milestones

Measure	Supplementary Dose Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Overall Study STARTED	53	55
Overall Study COMPLETED	51	52
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Standard Versus Double Dose Dolutegravir in Patients With HIV-associated Tuberculosis

Baseline characteristics by cohort

Measure	Supplementary Dose n=53 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=55 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	Total n=108 Participants Total of all reporting groups
Age, Continuous	33 years n=5 Participants	37 years n=7 Participants	35 years n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	19 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	36 Participants n=7 Participants	70 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	53 Participants n=5 Participants	55 Participants n=7 Participants	108 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment South Africa	53 participants n=5 Participants	55 participants n=7 Participants	108 participants n=5 Participants
HIV-1 RNA log10 Viral Load	5.1 log10 copies/mL n=5 Participants	5.2 log10 copies/mL n=7 Participants	5.2 log10 copies/mL n=5 Participants
CD4	197 cells/mm3 n=5 Participants	183 cells/mm3 n=7 Participants	188 cells/mm3 n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: mITT population at 24 weeks

Proportion with HIV viral load <50 copies/mL at 24 weeks analysed by modified intention to treat (ITT), which includes all participants who received at least one dose of dolutegravir, and according to the FDA snapshot algorithm.

Outcome measures

Measure	Supplementary Dose n=52 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=53 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Virological Suppression at 24 Weeks	43 Participants	44 Participants	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: mITT population at 12 weeks

Proportion with HIV viral load <50 copies/mL at 12 weeks analyzed modified ITT.

Outcome measures

Measure	Supplementary Dose n=53 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=55 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Virological Suppression at 12 Weeks (Modified ITT)	42 Participants	46 Participants	—	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Per protocol population at 24 weeks

Proportion with HIV viral load <50 copies/mL at 24 weeks analyzed per protocol.

Outcome measures

Measure	Supplementary Dose n=51 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=52 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Virological Suppression at 24 Weeks (Per Protocol)	43 Participants	44 Participants	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: mITT population at 48 weeks

Proportion with HIV viral load <50 copies/mL at 48 weeks analyzed modified ITT.

Outcome measures

Measure	Supplementary Dose n=49 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=52 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Virological Suppression at 48 Weeks (Modified ITT)	34 Participants	35 Participants	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: Per protocol population at week 48

Proportion with HIV viral load <50 copies/mL at 48 weeks analyzed per protocol.

Outcome measures

Measure	Supplementary Dose n=47 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=46 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Virological Suppression at 48 Weeks (Per Protocol)	34 Participants	35 Participants	—	—

SECONDARY outcome

Timeframe: 24 weeks

Population: mITT population

Change in CD4 count from screening at week 24.

Outcome measures

Measure	Supplementary Dose n=52 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=53 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
CD4 Change at 24 Weeks	111 cells/uL Interval 89.0 to 121.0	101 cells/uL Interval 84.0 to 114.0	—	—

SECONDARY outcome

Timeframe: 24 weeks

Population: Participants with available dolutegravir trough concentrations at week 24

Proportion with dolutegravir trough concentrations above the PA IC90 at week 24

Outcome measures

Measure	Supplementary Dose n=33 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=42 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Dolutegravir Trough Concentrations	32 Participants	34 Participants	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: Safety population

Grade 3 or 4 drug-related adverse events will be accessed throughout the trial.

Outcome measures

Measure	Supplementary Dose n=53 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=55 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Grade 3 or 4 Adverse Events	11 Participants	10 Participants	—	—

SECONDARY outcome

Timeframe: Through 48 weeks

Population: Safety population with available scores at baseline and with a baseline score \<=7

Insomnia severity index (ISI scored from 0-28. Score categories: 0-7, no clinical significant insomnia; 8-14, sub-threshold insomnia; 15-21, clinical insomnia (moderate severity); 22-28, clinical insomnia (severe). Measures sleep patterns and how this influences daily functioning and quality of life (assessed through 48 weeks). Measure of participants with treatment emergent insomnia from baseline

Outcome measures

Measure	Supplementary Dose n=51 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=52 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Change in Sleep Assessment From Baseline - Any Treatment Emergent Insomnia After Baseline Assessed at 4 Weekly Intervals Until Week 24 and Then Again at Week 48	10 Participants	4 Participants	—	—

SECONDARY outcome

Timeframe: Through 48 weeks

Population: Safety population (all participants with baseline assessments available).

Modified MINI screen (MMS) Mental health questionnaire will be assessed by given at baseline, 12 weeks, 24 weeks, and 48 weeks. The questionnaire is standardized and has been based on the mini international neuropsychiatric interview (version 7.0.0). All questions in the questionnaire require a yes/no answer.

MMS score increased is worsening MMS includes 22 questions answered yes/no; 2 questions related to experiencing a traumatic event were excluded for a 20 point scale.

MMS was measured at baseline, week 12, and week 24

Presenting number of participants with increase in MMS of at least 1 point from baseline through 48 weeks.

Outcome measures

Measure	Supplementary Dose n=53 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=55 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Change in Mental Health Assessment From Baseline Through Week 48	2 Participants	4 Participants	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: Safety population

Document any serious adverse events that occur throughout the trial.

Outcome measures

Measure	Supplementary Dose n=53 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=55 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Serious Adverse Events	0 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: 48 weeks

Any adverse event that requires discontinuation of any drug in the ART regimen throughout the trial.

Outcome measures

Measure	Supplementary Dose n=53 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=55 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Adverse Events Requiring Discontinuation of an ART Drug	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Through 48 weeks

Population: Safety population

If a viral load is >1000 copies/mL at week 24 or at week 48, or if the viral load was suppressed and then rebounded to >1000 copies/mL, a sample will be taken for resistance testing. Antiretroviral resistance mutations in participants with virologic failure will be assessed by genotypic resistance assay and compared to stored plasma at baseline to distinguish emergent from pre-treatment resistance.

Any ART resistance mutations in participants with virological failure by week 48.

Outcome measures

Measure	Supplementary Dose n=53 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=55 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Antiretroviral Resistance Mutations Testing by Genotypic Resistance Assay in Participants With Virologic Failure	3 Participants	3 Participants	—	—

SECONDARY outcome

Timeframe: 24 weeks

Population: mITT population

The primary outcome measure (proportion with HIV viral load <50 copies/mL at 24 weeks analysed by modified intention to treat (ITT), which includes all participants who received at least one dose of dolutegravir, and according to the FDA snapshot algorithm) will be stratified by ART-naïve versus first-line interruption status.

Outcome measures

Measure	Supplementary Dose n=43 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=42 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Supplemental Dolutegravir Arm n=9 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	First Line ART Interrupted Placebo Arm n=11 Participants Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Primary Outcome Differences Among ART-naïve Versus First-line Interruption Status	36 Participants	36 Participants	7 Participants	8 Participants

Adverse Events

Supplementary Dose

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo Dose

Serious events: 5 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Measure	Supplementary Dose n=53 participants at risk Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=55 participants at risk Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Gastrointestinal disorders Treatment resistant oesophageal candidiasis	0.00% 0/53 • 48 weeks	1.8% 1/55 • Number of events 1 • 48 weeks
Skin and subcutaneous tissue disorders Lichenoid rash secondary to TB treatment	0.00% 0/53 • 48 weeks	1.8% 1/55 • Number of events 1 • 48 weeks
Gastrointestinal disorders Bowel obstruction	0.00% 0/53 • 48 weeks	1.8% 1/55 • Number of events 1 • 48 weeks
Injury, poisoning and procedural complications Trauma	0.00% 0/53 • 48 weeks	1.8% 1/55 • Number of events 1 • 48 weeks
Respiratory, thoracic and mediastinal disorders Community acquired pneumonia	0.00% 0/53 • 48 weeks	1.8% 1/55 • Number of events 1 • 48 weeks

Other adverse events

Measure	Supplementary Dose n=53 participants at risk Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later. Dolutegravir 50 mg: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is given with a supplementary dose of dolutegravir 50 mg.	Placebo Dose n=55 participants at risk Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily with placebo taken 12 hours later. Placebo: Dolutegravir-lamivudine-tenofovir fixed-dose combination tablet daily is not given with a supplementary dose of dolutegravir 50 mg.
Nervous system disorders Insomnia	5.7% 3/53 • Number of events 3 • 48 weeks	0.00% 0/55 • 48 weeks

Additional Information

Prof Gary Maartens

University of Cape Town

Phone: 214066008

Email: gary.maartens@uct.ac.za

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place