In individuals with untreated HIV-1 infection, the two-drug dolutegravir/lamivudine (DTG/3TC) antiretroviral therapy (ART) regimen has similar efficacy as the three-drug bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) regimen, according to the phase IIIb VOGUE study.
At week 48, the primary endpoint of HIV-1 RNA <50 copies/mL was achieved in 89 percent of participants in the DTG/3TC group vs 92 percent of those in the BIC/FTC/TAF group. The adjusted difference of −3 percent (95 percent confidence interval [CI], −8 percent to 2 percent) fell within the noninferiority margin of –10 percent. [Open Forum Infect Dis 2026;doi:10.1093/ofid/ofag471]
“Rapid viral suppression was achieved in VOGUE,” said principal investigator Dr Jade Ghosn from Paris Cité University in France, who reported the results at the annual AIDS meeting.
The median time to suppression was 4.1 weeks in both treatment groups. Importantly, participants receiving DTG/3TC had a 23-percent greater likelihood of achieving virologic suppression compared with those receiving BIC/FTC/TAF (adjusted hazard ratio, 1.23, 95 percent CI, 1.03–1.47; p=0.0357), Ghosn noted.
When the clinically relevant threshold of 200 copies/mL was used, the rates of viral suppression were likewise similar in the DTG/3TC and BIC/FTC/TAF groups, at 94 percent and 93 percent, respectively (adjusted difference, 1 percent, 95 percent CI, −4 percent to 5 percent).
“VOGUE provides the first randomized, head-to-head evidence comparing two guideline-recommended, integrase strand transfer inhibitor (INSTI)-based therapies in the initial treatment setting,” Ghosn said. “The findings support DTG/3TC as a simplified option for adults starting ART, for whom durable virologic suppression, regimen simplicity, and cumulative antiretroviral exposure are important considerations.”
Clinically diverse population
VOGUE had a clinically diverse population without baseline viral load or CD4+ cell count restrictions and who initiated treatment before availability of genotypic resistance results. A total of 509 adults (median age 33 years, 16 percent female at birth) with untreated HIV-1 were randomly assigned to receive DTG/3TC (n=254) or BIC/FTC/TAF (n=255). Median time from screening to treatment initiation was 10 days.
Demographics and baseline characteristics were balanced between treatment groups. Overall, 47 percent of participants had baseline HIV-1 RNA ≥100,000 copies/mL, and 16 percent had baseline CD4+ cell count <200 cells/mm3.
“High rates of viral suppression were observed regardless of baseline HIV-1 RNA and regardless of baseline CD4+ cell count, with no significant between-group differences,” Ghosn said.
Viral suppression rates at week 48 in the DTG/3TC and BIC/FTC/TAF groups were 93 percent and 94 percent among those with baseline HIV-1 RNA <100,000 copies/mL, 85 percent and 89 percent among those with baseline HIV-1 RNA ≥100,000 copies/mL, 78 percent and 85 percent among those with baseline CD4+ cell count <200 cells/mm3, and 91 percent and 94 percent among those with baseline CD4+ cell count ≥200 cells/mm3. Results were similar when the 200 copies/mL threshold was used.
“CD4+ cell count recovery through week 48 was similar between the treatment groups,” Ghosn noted.
“The non-restrictive enrolment criteria in VOGUE enabled inclusion of populations frequently encountered in routine clinical practice, and the results [from the subgroup analysis] reinforce DTG/3TC as an effective, first-line, two-drug option for a broad population initiating ART when used in a test-and-treat approach,” he said.
Resistance and safety
By week 48, confirmed virologic withdrawal (ie, two consecutive plasma HIV-1 RNA measurements meeting criteria for either virologic non-response or virologic rebound [≥200 copies/mL]) occurred in 3 percent of participants each in the DTG/3TC and BIC/FTC/TAF groups.
“There was no treatment-emergent resistance observed in participants for whom resistance data was available at the time of confirmed virologic withdrawal,” Ghosn pointed out.
Safety profiles were also comparable between DTG/3TC and BIC/FTC/TAF, he added.
In the DTG/3TC and BIC/FTC/TAF groups, 10 percent and 11 percent had grade 3–4 adverse events (AEs), 17 percent and 19 percent had drug-related AEs, and 9 percent and 8 percent had serious AEs, respectively. The most common any-grade AEs were nasopharyngitis, headache, weight gain, and diarrhoea. AEs led to treatment discontinuation in 1 percent of participants in each group.
From baseline to week 48, weight increased by a mean of 3.6 kg in the DTG/3TC group and 4 kg in the BIC/FTC/TAF group. No new hepatitis B virus infections or reactivations were reported.
Unlikely to replace BIC/FTC/TAF
“I view [VOGUE] as reassuring about the efficacy of DTG/3TC as initial therapy, including in people with high viral loads or low CD4 counts... But while it provides more confidence in this approach, it doesn’t provide a reason to replace BIC/FTC/TAF when that regimen works so well as initial therapy and also provides hepatitis B treatment and prevention,” wrote Dr Paul Sax from Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, US, in his blog post on NEJM Voices.
“But when DTG is finally generic, will DTG/3TC be available at a low cost? We’ll see,” Sax concluded.