ViiV Healthcare Reports Dovato as Effective as Biktarvy for HIV-1 Maintenance

ViiV Healthcare, the global HIV-focused pharmaceutical company primarily owned by GSK, with Pfizer and Shionogi as shareholders, has announced significant findings from the PASO DOBLE (GeSIDA 11720 study). This marks the largest head-to-head, phase IV randomised clinical trial (RCT) comparing the 2-drug regimen Dovato (dolutegravir/lamivudine [DTG/3TC]) to the 3-drug regimen Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide fumarate [BIC/FTC/TAF]) for treating HIV-1 in virologically suppressed individuals who could benefit from optimized therapy.

The study, spanning 48 weeks, demonstrated that switching to DTG/3TC maintained non-inferior efficacy in viral suppression compared to BIC/FTC/TAF. These results will be presented at the 25th International AIDS Conference (AIDS 2024) in Munich, Germany.

Harmony P. Garges, M.D., MPH, Chief Medical Officer at ViiV Healthcare, highlighted the significance of these findings, noting that the average weight gain for participants on DTG/3TC was significantly lower than those on BIC/FTC/TAF over the year. This highlights the importance of addressing treatment-related weight gain for people living with HIV.

The PASO DOBLE trial involved 553 virally suppressed HIV-positive individuals. Participants were randomly assigned to either DTG/3TC (n=277) or BIC/FTC/TAF (n=276). The study included individuals on multiple tablet regimens or those containing pharmacokinetic boosting agents or drugs with cumulative toxicity, like efavirenz or tenofovir disoproxil fumarate (TDF).

The study's primary endpoint was achieved, demonstrating non-inferior efficacy of DTG/3TC compared to BIC/FTC/TAF based on the proportion of participants with viral RNA ≥50 copies/mL at 48 weeks, with a margin of 4% non-inferiority. DTG/3TC was found to be non-inferior to BIC/FTC/TAF, with a risk difference of 1.4%. One participant in the BIC/FTC/TAF group and none in the DTG/3TC group experienced protocol-defined confirmed virological failure through week 48.

A key secondary endpoint revealed that weight gain was significantly higher in participants who switched to BIC/FTC/TAF (adjusted mean change 1.81kg) compared to those who switched to DTG/3TC (adjusted mean change 0.89kg). Furthermore, the proportion of participants with over 5% weight gain at 48 weeks was 29.9% for BIC/FTC/TAF, compared to 20% for DTG/3TC. Weight change with DTG/3TC did not differ between men and women or based on previous regimens, whereas the proportion of participants experiencing over 5% weight gain was higher with BIC/FTC/TAF when switching from regimens containing abacavir or TDF.

Safety profiles were consistent across both study arms, with few discontinuations due to adverse events (DTG/3TC = 1, BIC/FTC/TAF = 2).

Esteban Martínez, MD, PhD, Chief Executive Investigator of the PASO DOBLE study and Senior Consultant in Infectious Diseases at Hospital Clínic of Barcelona, stated that the current HIV treatment regimens are highly effective, and it’s crucial to study their impacts beyond viral suppression. The results indicate that Dovato not only maintains efficacy but also shows less weight gain compared to BIC/FTC/TAF over 48 weeks.

The PASO DOBLE trial, conducted across 30 sites in Spain, evaluated the efficacy of DTG/3TC versus BIC/FTC/TAF for maintaining virologic suppression in HIV-1 patients. The trial involved virologically suppressed individuals on regimens including multiple pills per day, boosters, or drugs with cumulative toxicity.

Dovato is approved globally as a complete regimen for treating HIV-1 in adults with no antiretroviral treatment history or those virologically suppressed on a stable regimen. It is available in the US, Europe, Japan, Australia, and other countries worldwide.