Can People Starting HIV Treatment Use One Less Drug? Dovato Is Non-Inferior to Biktarvy in First Head-to-Head Trial

HIV treatment often continues for decades, so whether one fewer antiviral drug can be used while maintaining viral suppression is more than merely a difference in a tablet’s list of ingredients. VOGUE, the first trial to directly compare two commonly used initial treatment regimens, showed that the two-drug combination Dovato was non-inferior to the three-drug combination Biktarvy in efficacy at 48 weeks, providing new randomized-trial evidence for simplifying first-line treatment.

This open-label, multinational phase IIIb trial enrolled 509 adults with HIV-1 who had not previously received treatment. Participants were randomly assigned to receive Dovato (dolutegravir/lamivudine; 254 people) or Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide; 255 people). Participants began treatment before their genotypic drug-resistance test results became available, more closely reflecting the clinical setting of “test and treat” in some regions.

At week 48, 89% of the Dovato group had reduced their viral load to below 50 copies of RNA per milliliter, compared with 92% of the Biktarvy group. The adjusted difference was minus 3 percentage points, with a 95% confidence interval of minus 8 to 2 percentage points, which did not cross the prespecified non-inferiority margin of minus 10%. The median time to viral suppression was 4.1 weeks in both groups, and no treatment-emergent drug resistance was detected during the treatment period.

The trial set no upper or lower enrollment limits for viral load or CD4 cell count: 16% of participants had a baseline viral load of at least 500,000 copies per milliliter, while another 16% had a CD4 cell count below 200 cells per cubic millimeter. The study report stated that the two-drug regimen maintained similar efficacy in stratified analyses of participants with high viral loads or low CD4 counts. Mean increases in CD4 cell counts at week 48 were also similar, rising by 232 and 236 cells in the two groups, respectively.

No new safety signals emerged, and there were no serious drug-related adverse events. Mean weight increased by 3.6 kilograms in the Dovato group and 4.0 kilograms in the Biktarvy group. Seven people in each group discontinued treatment because they did not achieve or maintain viral suppression. The conference report further specified that seven people in the Dovato group and six in the Biktarvy group experienced viral rebound, while one additional Biktarvy user never achieved viral suppression.

Background

The earlier GEMINI trials supported dolutegravir/lamivudine as an initial treatment option, but VOGUE is its first randomized head-to-head comparison with the widely used Biktarvy. The result addresses whether efficacy is no worse by more than a prespecified margin; it does not prove that Dovato is more effective, nor can fewer drug components alone be used to infer lower long-term toxicity. The study excluded people with active hepatitis B, whose treatment generally must also account for HBV suppression.

VOGUE will continue follow-up through week 96, with subsequent endpoints including sustained viral suppression, drug resistance, safety, and weight changes. The data currently available come mainly from a pharmaceutical company announcement and a report presented at an international AIDS conference, while full peer-reviewed results have yet to be published. Participants were 84% male and only 17% were non-White, which also limits certainty about the generalizability of the results to more diverse populations.