A Randomized Clinical Trial to Evaluate Solutions for the Management of Virologic Failure on TLD in Sub-Saharan Africa

The RESOLVE trial is an open, parallel arm, randomized clinical trial which aims to determine the optimal strategy for management of virologic failure on first-line antiretroviral therapy (ART) with tenofovir, lamivudine, and dolutegravir (TLD) in sub-Saharan Africa. The primary outcome of interest will be viral suppression to <50 copies/mL at 48 weeks using the FDA snapshot definition. The study will be conducted in Uganda and South Africa.

The RESOLVE trial is an open, parallel arm, randomized clinical trial which will be conducted at public-sector HIV clinics in Uganda and South Africa. We will enroll individuals with HIV age 15 and above who have had two HIV-1 RNA viral load results >1,000 copies/mL while on TLD as first-line antiretroviral therapy and who have been on TLD for at least 12 months. Participants will be randomized using an equal allocation ratio of 1:1:1 across three study arms : 1) Maintenance on TLD with switch to protease inhibitor (PI)-based second-line ART if virologic failure persists past six months, 2) Individualized Care with regimen choice based on results of genotypic resistance tests and urine tenofovir adherence assays, or 3) Immediate Switch to PI-based second-line ART. Randomization will be stratified by clinic and prior exposure to non-nucleoside reverse transcriptase inhibitors. We will follow participants for one year with study visits at enrollment, Week 24, and Week 48. The primary outcome of interest will be viral suppression to <50 copies/mL at 48 weeks using the FDA snapshot definition.