Trial Outcomes & Findings for Tenofovir-lamivudine-dolutegravir Combination as Second-line ART: a Randomised Controlled Trial (NCT NCT03991013)
NCT ID: NCT03991013
Last Updated: 2024-10-01
Results Overview
Proportion of participants with HIV viral load \<50 copies/mL at 24 weeks analysed by modified intention to treat (ITT) and according to the FDA snapshot algorithm
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
192 participants
Primary outcome timeframe
24 weeks
Results posted on
2024-10-01
Participant Flow
Stage 1 of the ARTIST study was a single-arm prospective cohort study of second-line TLD regimen with supplementary dolutegravir dose (50 mg twice daily) for two weeks in patients failing a NNRTI-based regimen. After completion of stage 1, the study progressed to enrol 130 participants in stage 2.
Participant milestones
| Measure |
Stage 2: Supplementary Dose
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
Overall Study
STARTED
|
65
|
65
|
62
|
|
Overall Study
COMPLETED
|
64
|
63
|
62
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Denominators indicate the numbers of participants with available viral sequences.
Baseline characteristics by cohort
| Measure |
Stage 2: Supplementary Dose
n=65 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=65 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=62 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Total
n=192 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
38 years
n=65 Participants
|
39 years
n=65 Participants
|
37 years
n=62 Participants
|
38 years
n=192 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=65 Participants
|
47 Participants
n=65 Participants
|
43 Participants
n=62 Participants
|
132 Participants
n=192 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=65 Participants
|
18 Participants
n=65 Participants
|
19 Participants
n=62 Participants
|
60 Participants
n=192 Participants
|
|
Race/Ethnicity, Customized
Black
|
65 Participants
n=65 Participants
|
65 Participants
n=65 Participants
|
62 Participants
n=62 Participants
|
192 Participants
n=192 Participants
|
|
Weight
|
74 kg
n=65 Participants
|
80 kg
n=65 Participants
|
71 kg
n=62 Participants
|
77 kg
n=192 Participants
|
|
BMI
|
28.4 kg/m2
n=65 Participants
|
30.1 kg/m2
n=65 Participants
|
27.8 kg/m2
n=62 Participants
|
29.0 kg/m2
n=192 Participants
|
|
CD4 cell count
|
246 cells/μL
n=65 Participants
|
250 cells/μL
n=65 Participants
|
259 cells/μL
n=62 Participants
|
246 cells/μL
n=192 Participants
|
|
HIV-1 RNA
|
4.12 log10 copies/mL
n=65 Participants
|
4.01 log10 copies/mL
n=65 Participants
|
3.98 log10 copies/mL
n=62 Participants
|
4.02 log10 copies/mL
n=192 Participants
|
|
Time receiving first-line ART
|
77 months
n=65 Participants
|
93 months
n=65 Participants
|
62 months
n=62 Participants
|
88 months
n=192 Participants
|
|
Two fully active NRTIs
|
2 Participants
n=63 Participants • Denominators indicate the numbers of participants with available viral sequences.
|
2 Participants
n=57 Participants • Denominators indicate the numbers of participants with available viral sequences.
|
6 Participants
n=56 Participants • Denominators indicate the numbers of participants with available viral sequences.
|
10 Participants
n=176 Participants • Denominators indicate the numbers of participants with available viral sequences.
|
|
Resistance to 1 NRTI
|
15 Participants
n=63 Participants • Denominators indicate the numbers of participants with available viral sequences
|
10 Participants
n=57 Participants • Denominators indicate the numbers of participants with available viral sequences
|
14 Participants
n=56 Participants • Denominators indicate the numbers of participants with available viral sequences
|
39 Participants
n=176 Participants • Denominators indicate the numbers of participants with available viral sequences
|
|
Resistance to both NRTIs
|
46 Participants
n=63 Participants • Denominators indicate the numbers of participants with available viral sequences
|
45 Participants
n=57 Participants • Denominators indicate the numbers of participants with available viral sequences
|
36 Participants
n=56 Participants • Denominators indicate the numbers of participants with available viral sequences
|
127 Participants
n=176 Participants • Denominators indicate the numbers of participants with available viral sequences
|
|
TFV-DP concentration
|
948 fmol/punch
n=65 Participants
|
1052 fmol/punch
n=65 Participants
|
1186 fmol/punch
n=62 Participants
|
960 fmol/punch
n=192 Participants
|
PRIMARY outcome
Timeframe: 24 weeksPopulation: mITT analysis excludes those switching study drug for reasons of stopping contraception or desire to become pregnant, becoming pregnant, transfer out for nonclinical reasons, and death from non-HIV and nondrug causes.
Proportion of participants with HIV viral load \<50 copies/mL at 24 weeks analysed by modified intention to treat (ITT) and according to the FDA snapshot algorithm
Outcome measures
| Measure |
Stage 2: Supplementary Dose
n=64 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=65 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=62 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
Virological Suppression at 24 Weeks
|
55 Participants
|
53 Participants
|
53 Participants
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: Sensitivity analysis excludes those excluded from mITT analysis, as well as loss to follow-up, missing viral load within the window, switching study drug for reasons other than treatment failure, and evidence of poor adherence (tenofovir diphosphate \<350 fmol/punch).
Proportion of participants with HIV viral load \<50 copies/mL at 24 weeks using pre-specified sensitivity analyses
Outcome measures
| Measure |
Stage 2: Supplementary Dose
n=64 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=61 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=60 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
Virological Suppression at 24 Weeks (Sensitivity Analysis)
|
55 Participants
|
53 Participants
|
53 Participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: mITT analysis excludes those switching study drug for reasons of stopping contraception or desire to become pregnant, becoming pregnant, transfer out for nonclinical reasons, and death from non-HIV and nondrug causes.
Proportion of participants with HIV viral load \<50 copies/mL at 12 weeks analysed by modified ITT.
Outcome measures
| Measure |
Stage 2: Supplementary Dose
n=64 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=65 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=60 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
Virological Suppression at 12 Weeks (Modified ITT)
|
53 Participants
|
55 Participants
|
45 Participants
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: If any HIV-1 RNA after week 12 was ≥50 copies/mL, or if there was \<1 log10 decline in HIV-1 RNA from baseline, or if HIV-1 RNA was suppressed and sub- sequently rebound to ≥50 copies/mL, enhanced adherence counseling was performed, and HIV-1 RNA measurement was repeated after 2 weeks. If the repeat HIV-1 RNA was ≥500 copies/mL, a genotypic antiretroviral resistance test was performed.
To describe dolutegravir resistance or emergent resistance mutations to tenofovir or lamivudine in participants eligible for genotypic resistance testing by 24 weeks
Outcome measures
| Measure |
Stage 2: Supplementary Dose
n=3 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=3 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=1 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
Antiretroviral Resistance Mutations by Genotypic Resistance Testing
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 24 weeksChange in CD4 count from screening to week 24
Outcome measures
| Measure |
Stage 2: Supplementary Dose
n=65 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=65 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=62 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
CD4 Change at 24 Weeks
|
88 cells/μL
Interval 45.0 to 138.0
|
75 cells/μL
Interval 18.0 to 127.0
|
99 cells/μL
Interval 36.0 to 163.0
|
SECONDARY outcome
Timeframe: 24 weeksTo describe grade 3 or 4 adverse events and serious adverse events
Outcome measures
| Measure |
Stage 2: Supplementary Dose
n=65 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=65 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=62 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
Adverse Events
|
4 Participants
|
5 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: 24 weeksTo describe all-cause mortality.
Outcome measures
| Measure |
Stage 2: Supplementary Dose
n=65 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=65 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=62 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
All-cause Mortality
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: We monitored adherence with tenofovir diphosphate (TFV-DP) concentrations using stored dried blood spot specimens.
To describe tenofovir-diphosphate (TFV-DP) concentrations (ng/mL) at 24 weeks
Outcome measures
| Measure |
Stage 2: Supplementary Dose
n=63 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=64 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=62 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
Adherence to Treatment
|
1354 fmol/punch
Interval 930.0 to 1873.0
|
1393 fmol/punch
Interval 1098.0 to 1811.0
|
1186 fmol/punch
Interval 859.0 to 1905.0
|
SECONDARY outcome
Timeframe: First 28 daysTo evaluate the geometric mean ratio (GMR) of dolutegravir trough concentrations on day 7 versus day 28
Outcome measures
| Measure |
Stage 2: Supplementary Dose
n=13 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=11 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=12 Participants
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
Geometric Mean Ratio (GMR) of Dolutegravir Trough Concentrations on Day 7 Versus Day 28
|
1.654 ratio
Interval 1.404 to 1.948
|
0.637 ratio
Interval 0.485 to 0.837
|
1.654 ratio
Interval 1.404 to 1.948
|
Adverse Events
Stage 2: Supplementary Dose
Serious events: 2 serious events
Other events: 2 other events
Deaths: 1 deaths
Stage 2: Placebo Dose
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
Serious events: 9 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Stage 2: Supplementary Dose
n=65 participants at risk
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=65 participants at risk
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=62 participants at risk
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
Infections and infestations
severe COVID-19
|
1.5%
1/65 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/62 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Psychiatric disorders
acute psychosis
|
1.5%
1/65 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/62 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Injury, poisoning and procedural complications
fractured tibia
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Blood and lymphatic system disorders
thrombocytopenia
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Renal and urinary disorders
urinary tract infection
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
incident pulmonary tuberculosis
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Injury, poisoning and procedural complications
stab chest
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Renal and urinary disorders
acute kidney injury
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Gastrointestinal disorders
gastritis
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Gastrointestinal disorders
perianal abscess
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Skin and subcutaneous tissue disorders
condylomata acuminata
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
Other adverse events
| Measure |
Stage 2: Supplementary Dose
n=65 participants at risk
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 2: Placebo Dose
n=65 participants at risk
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with a matching placebo taken 12 hours later for the first 14 days.
Placebo: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a matching placebo taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
Stage 1: TLD Regimen With Supplementary Dolutegravir Dose
n=62 participants at risk
Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet daily with an additional dolutegravir 50 mg dose taken 12 hours later for the first 14 days.
Dolutegravir 50 mg: Tenofovir-lamivudine-dolutegravir fixed-dose combination tablet with a lead-in supplementary dose of 50 mg dolutegravir taken 12 hours later for the first 14 days, with continuation of tenofovir-lamivudine-dolutegravir for the duration of the study (48 weeks).
|
|---|---|---|---|
|
Psychiatric disorders
acute psychosis
|
1.5%
1/65 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/62 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Infections and infestations
incident pulmonary tuberculosis
|
1.5%
1/65 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/62 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Endocrine disorders
raised random glucose
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
3.1%
2/65 • Number of events 2 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/62 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Renal and urinary disorders
acute kidney injury
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
3.1%
2/65 • Number of events 2 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Nervous system disorders
headache
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.5%
1/65 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/62 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Blood and lymphatic system disorders
neutropenia
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
|
Cardiac disorders
raised blood pressure
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
0.00%
0/65 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
1.6%
1/62 • Number of events 1 • 48 weeks
Adverse events were evaluated and graded at all study visits according to the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place