Phase IIIb VOGUE trial shows Dovato achieved non-inferior Week 48 virologic suppression versus Biktarvy with no treatment-emergent resistance in adults with HIV-1.
Written By: Mayuresh Salvi, PharmD
Reviewed By: Pharmacally Editorial Team
Topline Week 48 results from the Phase IIIb VOGUE study (NCT05979311) showed that ViiV Healthcare’s two-drug regimen Dovato (dolutegravir/lamivudine; DTG/3TC) achieved non-inferior virologic suppression compared with Gilead Sciences’ three-drug regimen Biktarvy (Bictegravir/emtricitabine/tenofovir alafenamide; BIC/FTC/TAF) in treatment-naïve adults living with HIV-1. The study met its primary endpoint, with Dovato demonstrating comparable efficacy, rapid viral suppression, and no treatment-emergent resistance, marking the first randomized head-to-head comparison between the two leading first-line antiretroviral regimens.
Dovato Demonstrates Non-Inferior Week 48 Efficacy
The ongoing multicountry, open-label, Phase IIIb VOGUE study randomized 509 treatment-naïve adults living with HIV-1 to receive either once-daily Dovato (n=254) or Biktarvy (n=255). Treatment was initiated before baseline resistance testing results became available, reflecting real-world clinical practice.
At Week 48, virologic suppression (HIV-1 RNA <50 copies/mL) was achieved in 89% (226/254) of participants receiving Dovato compared with 92% (235/255) receiving Biktarvy. The adjusted treatment difference was -3% (95% confidence interval: -8% to 2%), meeting the study’s predefined non-inferiority endpoint.
Median time to virologic suppression was rapid and identical in both treatment groups at 4.1 weeks, demonstrating that the two-drug regimen achieved viral control comparable to the three-drug standard.
Dovato maintained efficacy across clinically important subgroups. At study entry, 47% of participants had baseline HIV-1 RNA levels of at least 100,000 copies/mL, including 16% with viral loads of at least 500,000 copies/mL, while 16% had CD4+ cell counts below 200 cells/mm³.
No Treatment-Emergent Resistance Observed
No cases of treatment-emergent resistance were identified in either treatment arm during the 48-week study. These findings further reinforce the high genetic barrier to resistance associated with dolutegravir-containing therapy and support the durability of Dovato as a first-line treatment option for adults initiating antiretroviral therapy.
Safety Findings
Both treatment regimens demonstrated comparable overall safety profiles, with no new safety signals observed during the study. Seven participants in each treatment arm discontinued therapy because they did not achieve or maintain virologic suppression, indicating similar treatment durability across both groups.
ViiV Highlights Benefits of Treatment Simplification
Jean van Wyk, MBChB, MFPM, Chief Medical Officer at ViiV Healthcare, said the findings reinforce more than a decade of evidence supporting Dovato as an effective first-line treatment while reducing the number of antiretroviral medicines people receive over a lifetime.
He noted that VOGUE, as the first randomized head-to-head study comparing Dovato with Biktarvy in treatment-naïve adults, demonstrates that eligible people living with HIV can begin treatment with fewer daily antiretroviral medicines without compromising efficacy or the barrier to resistance.
Why These Findings Matter
Combination antiretroviral therapy (ART) has transformed HIV infection into a manageable chronic condition, enabling people living with HIV to achieve sustained viral suppression and near-normal life expectancy. Although three-drug regimens have long been considered the standard of care, advances in HIV treatment have shown that appropriately selected two-drug regimens can maintain durable viral suppression while reducing lifetime exposure to antiretroviral medications.
The VOGUE study directly addresses one of the most important questions in contemporary HIV care by comparing a two-drug regimen with one of the world’s most widely prescribed three-drug first-line therapies. Demonstrating non-inferior efficacy against Biktarvy provides additional evidence supporting treatment simplification for eligible patients without compromising virologic outcomes or resistance protection.
About the Phase IIIb VOGUE Study
VOGUE is an ongoing multicountry, open-label, randomized Phase IIIb study evaluating Dovato versus Biktarvy in treatment-naïve adults living with HIV-1. Participants initiated treatment before baseline resistance testing results were available, allowing investigators to assess the performance of both regimens under conditions that closely reflect routine clinical practice.
The primary endpoint was the proportion of participants achieving plasma HIV-1 RNA levels below 50 copies/mL at Week 48. Secondary assessments included time to virologic suppression, safety, treatment discontinuation, and resistance monitoring.
About Dovato and Biktarvy
Dovato is a once-daily fixed-dose combination of the integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleoside reverse transcriptase inhibitor (NRTI) lamivudine. It is the first and only approved oral two-drug regimen for treatment-naïve adults living with HIV-1 who have no known or suspected resistance to either component.
Biktarvy combines the INSTI bictegravir with the NRTIs emtricitabine and tenofovir alafenamide (TAF) in a once-daily three-drug regimen and is widely used as a first-line treatment for HIV-1 infection worldwide.
Clinical Path Forward
The Week 48 VOGUE results further strengthen the clinical evidence supporting simplified antiretroviral therapy for treatment-naïve adults living with HIV. By demonstrating comparable efficacy, rapid virologic suppression, and an absence of treatment-emergent resistance in the first direct comparison with Biktarvy, Dovato offers clinicians additional confidence in selecting a two-drug regimen for appropriate patients while reducing lifetime exposure to antiretroviral medicines.
Longer-term follow-up evaluating the durability of viral suppression, resistance development, metabolic outcomes, and patient-reported quality of life will further define the comparative benefits of two-drug therapy and help inform future HIV treatment strategies.
What This Means for Patients
For people newly diagnosed with HIV, the VOGUE study provides additional evidence that effective treatment may not always require three antiretroviral medicines. The findings show that the two-drug regimen Dovato achieved viral suppression comparable to the three-drug regimen Biktarvy while maintaining a high barrier to resistance and a similar safety profile through 48 weeks.
Because HIV treatment is lifelong, reducing the number of medicines taken each day may help minimize cumulative drug exposure without compromising treatment effectiveness in appropriately selected patients. However, treatment decisions should always be individualized based on factors such as baseline drug resistance, hepatitis B virus co-infection, other medical conditions, and potential drug interactions. Patients should not change or stop their HIV medications without consulting their healthcare provider.
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About the Writer
Mayuresh Sunil Salvi (Linkedin) is a PharmD professional and healthcare writer with a strong interest in pharmacovigilance, drug safety, and emerging medical research. He is passionate about exploring new drug discoveries, clinical research, and advances in evidence-based medicine. His interests also include ward rounds, prescription audits, and treatment analysis to support rational pharmacotherapy and improved patient care.