Phase 2
N=108
Standard Versus Double Dose Dolutegravir in Patients With HIV-associated Tuberculosis
HIV Infections · Tuberculosis
Bottom Line
View on ClinicalTrials.gov: NCT03851588 ↗Enrolled (actual)
108
Serious AEs
4.6%
Results posted
Sep 2023
Primary outcome: Primary: Virological Suppression at 24 Weeks — 43; 44 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Placebo (Other); Dolutegravir 50 mg (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Cape Town
- Primary completion
- Jan 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Virological Suppression at 24 Weeks |
43; 44 | — |
| SECONDARY Virological Suppression at 12 Weeks (Modified ITT) |
42; 46 | — |
| SECONDARY Virological Suppression at 24 Weeks (Per Protocol) |
43; 44 | — |
| SECONDARY Virological Suppression at 48 Weeks (Modified ITT) |
34; 35 | — |
| SECONDARY Virological Suppression at 48 Weeks (Per Protocol) |
34; 35 | — |
| SECONDARY CD4 Change at 24 Weeks |
111; 101 | — |
| SECONDARY Dolutegravir Trough Concentrations |
32; 34 | — |
| SECONDARY Grade 3 or 4 Adverse Events |
11; 10 | — |
| SECONDARY 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; 4 | — |
| SECONDARY Change in Mental Health Assessment From Baseline Through Week 48 |
2; 4 | — |
| SECONDARY Serious Adverse Events |
0; 5 | — |
| SECONDARY Adverse Events Requiring Discontinuation of an ART Drug |
0; 0 | — |
| SECONDARY Antiretroviral Resistance Mutations Testing by Genotypic Resistance Assay in Participants With Virologic Failure |
3; 3 | — |
| SECONDARY Primary Outcome Differences Among ART-naïve Versus First-line Interruption Status |
36; 36; 7; 8 | — |
Summary
The investigators propose to conduct a phase 2 randomised (1:1) double-blind placebo-controlled trial of the dolutegravir-lamivudine-tenofovir fixed dose combination tablet daily with an additional 50 mg dose of dolutegravir/matching placebo taken 12 hours later in ART-naïve or fisrt-line interrupted HIV-infected patients on rifampicin-based anti-tuberculosis therapy. The hypothesis is that virologic outcomes with standard dose dolutegravir-based ART will be acceptable in patients on rifampicin-based anti-tuberculosis therapy.
Eligibility Criteria
Inclusion Criteria
- HIV-1 infection as documented by screening plasma HIV-1 RNA >1000 c/mL
- ART-naïve (short-term antiretroviral use for prevention of mother-to-child transmission will be allowed) or
- ART treatment interrupters on ART 100 cells/µL
- Women of child-bearing potential willing to use adequate contraception (defined as either an intrauterine contraceptive device or hormonal contraception as per national guidelines)
Exclusion Criteria
- Pregnant/breastfeeding
- Estimated glomerular filtration rate (eGFR) 3 times upper limit of normal (ULN)
- Allergy or intolerance to one of the drugs in regimen
- Concomitant medication known to significantly reduce or increase dolutegravir exposure (except rifampicin)
- Active psychiatric disease or substance abuse
- On treatment for active AIDS-defining condition other than tuberculosis (participants on maintenance therapy may be enrolled)
- Malignancy
- Any other clinical condition that in the opinion of an investigator puts the patient at increased risk of participating in the study.
Data sourced from ClinicalTrials.gov (NCT03851588). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.