ViiV's two-drug Dovato matches three-drug Biktarvy in first head-to-head HIV trial

ViiV Healthcare reported Week 48 data from the phase IIIb VOGUE study showing that dolutegravir/lamivudine (Dovato) met a non-inferiority endpoint against Gilead Sciences' Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) in treatment-naïve adults with HIV-1. The results, presented at the 26th International AIDS Conference in Rio de Janeiro, mark the first randomised head-to-head trial comparing the two-drug regimen directly against the three-drug standard in this population.

The results potentially have commercial implications. Biktarvy is the dominant oral first-line regimen globally, and demonstrating equivalent viral suppression with one fewer antiretroviral drug gives ViiV a direct argument for prescribers weighing pill burden over decades of treatment. Dovato is already approved in the US and EU for treatment-naïve adults and for virologically suppressed patients switching regimens.

The VOGUE study enrolled 509 treatment-naïve adults living with HIV-1, randomised to dolutegravir/lamivudine (n=254) or bictegravir/emtricitabine/tenofovir alafenamide (n=255), with treatment initiated before baseline resistance results were available. The population included patients with high viral loads — 47% had HIV-1 RNA ≥100,000 copies/mL, 16% had ≥500,000 copies/mL — and 16% had a CD4+ cell count below 200 cells/mm³, a subgroup historically considered higher risk for two-drug initiation. At Week 48, virologic suppression (HIV-1 RNA <50 copies/mL) was achieved in 89% of the dolutegravir/lamivudine arm versus 92% in the bictegravir/emtricitabine/tenofovir alafenamide arm (adjusted difference: -3%, 95% CI [-8%, 2%]), meeting the non-inferiority margin. Median time to viral suppression was 4.1 weeks in both arms. No treatment-emergent resistance was identified in either group, and safety profiles were comparable with no new signals.

Dolutegravir inhibits HIV-1 integrase by blocking strand transfer of viral DNA into the host genome; lamivudine adds reverse transcriptase inhibition, terminating viral DNA chain elongation. The combination omits the nucleotide reverse transcriptase inhibitor backbone that underpins three-drug regimens including bictegravir/emtricitabine/tenofovir alafenamide.

The resistance finding carries particular weight. Prior concerns about two-drug initiation centred on whether a single NRTI backbone partner would provide sufficient coverage before baseline resistance results were available — a real-world scenario given that testing delays are common in many settings. Zero emergent resistance across both arms, including in patients with very high viral loads, directly addresses that concern.

The VOGUE data extend a growing evidence base. The PASO DOBLE trial previously demonstrated non-inferior virologic maintenance with dolutegravir/lamivudine versus bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed patients switching regimens, and also reported statistically significant less weight gain with the two-drug regimen at 96 weeks. VOGUE now establishes comparable suppression from treatment initiation, including in populations previously excluded from pivotal trials.

Gilead's Biktarvy retains guideline-preferred status and broader label flexibility, including use in patients with hepatitis B co-infection, where lamivudine monotherapy is insufficient. That constraint limits dolutegravir/lamivudine's addressable population and will continue to require pre-treatment screening. The ongoing VOGUE study will provide longer-term follow-up data to assess durability of the non-inferiority finding.

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