ViiV Healthcare announced 96-week results from the PASO DOBLE clinical trial demonstrating that Dovato (dolutegravir/lamivudine) maintains viral suppression as effectively as Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide fumarate) while offering significant advantages in weight management and tolerability for HIV-1 patients. The findings, presented at the European AIDS Clinical Society annual congress in Paris, represent the largest head-to-head comparison between these two leading HIV treatment regimens.
Trial Design and Patient Population
The PASO DOBLE study enrolled 553 virologically suppressed adults with HIV-1 across 30 sites in Spain, randomizing participants 1:1 to switch to either Dovato (n=277) or Biktarvy (n=276). The phase IV, open-label, multicenter trial specifically targeted patients on suboptimal regimens that could benefit from treatment optimization, including those taking multiple daily tablets, pharmacokinetic boosting agents, or drugs with cumulative toxicity such as efavirenz or tenofovir disoproxil fumarate.
"For people living with HIV, achieving and maintaining viral suppression remains the cornerstone of effective treatment. However, HIV treatment options have now advanced to where we can also look to other health metrics to help define success," said Jean van Wyk, Chief Medical Officer at ViiV Healthcare.
Primary Efficacy Outcomes
Dovato met the study's primary endpoint, demonstrating non-inferior efficacy to Biktarvy in maintaining viral suppression at 96 weeks. The risk difference between treatment arms was -0.7% (95% CI -2.1 to 0.7), with Dovato showing a virological failure rate of 0.4% compared to 1.1% for Biktarvy using FDA snapshot analysis with a 4% non-inferiority margin.
Notably, zero participants in the Dovato arm experienced protocol-defined virological failure through week 96, compared to three participants in the Biktarvy arm. No resistance mutations were observed in any cases of virological failure, and the Biktarvy arm showed an increase of two additional virological failures since the initially reported 48-week data.
Weight Gain and Metabolic Advantages
The trial was specifically powered to assess weight gain as a key secondary endpoint, revealing statistically significant differences between treatment arms. Patients receiving Biktarvy experienced a mean adjusted weight gain of 2.35kg (95% CI 1.61-3.09) compared to 0.84kg (95% CI 0.09-1.60) with Dovato through 96 weeks, representing a difference of 1.52kg (95% CI 0.74-2.29).
The weight gain disparity between arms increased over time, growing from 1.13kg at 48 weeks to 1.52kg at 96 weeks. A significantly higher proportion of participants on Biktarvy experienced greater than 5% weight increase (34.8%) compared to those on Dovato (20.1%), with an adjusted odds ratio of 2.05 (95% CI 1.37-3.07).
"This 96-week data from PASO DOBLE underscores a favorable profile for Dovato, particularly regarding weight gain, which is an important consideration for virologically suppressed adults that may be on treatment for decades," said Esteban Martínez, Chief Executive Investigator of the PASO DOBLE study and Senior Consultant in Infectious Diseases at Hospital Clínic of Barcelona, Spain.
Safety and Tolerability Profile
Drug-related adverse events occurred less frequently with Dovato (7.6%) compared to Biktarvy (13.4%), achieving statistical significance (p=0.025). Six participants discontinued treatment due to adverse events, primarily neuropsychiatric in nature, with two discontinuations in the Dovato arm versus four in the Biktarvy arm, though this difference was not statistically significant (p=0.409).
The most common adverse reactions with Dovato included headache (3%), nausea (2%), diarrhea (2%), insomnia (2%), fatigue (2%), and anxiety (2%). The safety profile remained consistent with previous studies of the two-drug regimen.
Clinical Implications for HIV Treatment
The results support the potential for treatment simplification in HIV care, demonstrating that a two-drug regimen can maintain efficacy while offering metabolic advantages over a three-drug combination. This finding is particularly relevant for patients requiring long-term antiretroviral therapy, where cumulative effects of weight gain and drug-related adverse events can impact quality of life and cardiovascular risk profiles.
The study's design specifically addressed real-world clinical scenarios by enrolling patients on regimens that could benefit from optimization, making the findings directly applicable to current HIV treatment practices. The sustained efficacy through 96 weeks provides confidence for long-term treatment decisions in virologically suppressed patients.
ViiV Healthcare, the global specialist HIV company majority owned by GSK with Pfizer and Shionogi as shareholders, continues to focus on developing patient-centric treatment options that address needs beyond viral suppression, including long-term health management considerations for people living with HIV.
