The largest head-to-head randomized clinical trial confirms results and also shows the 2-therapy regimen led to less weight gain.
Image credit: ViiV
At this week’s International AIDS Society 2024 conference, ViiV Healthcare is presenting data demonstrating its HIV therapy, dolutegravir/lamivudine (Dovato), was non-inferior to bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), when switched. The former is a 2-drug regimen and the latter is a 3-drug regimen.1
The findings come from the PASO DOBLE clinical trial which entailed a 48-week period, a phase 4 randomized clinical trial. The study included 553 people living with HIV and virally suppressed switched treatment to either dolutegravir/lamivudine (n=277) or bictegravir/emtricitabine/tenofovir alafenamide (n=276).1
The study population included individuals who were on therapy that could be optimized, such as multiple tablet regimens, or those containing pharmacokinetic boosting agents or drugs with cumulative toxicity, such as efavirenz or tenofovir disoproxil fumarate (TDF). The study met its primary endpoint when dolutegravir/lamivudine demonstrated non-inferior efficacy versus bictegravir/emtricitabine/tenofovir alafenamide based on the proportion of participants with viral RNA ≥50 copies/mL at 48 weeks using the FDA snapshot and a 4% non-inferiority margin in the exposed intention-to-treat population.1
“The results from PASO DOBLE show that Dovato demonstrated non-inferior efficacy compared to Biktarvy,” Viiv Healthcare CMO Harmony P. Garges, MD, MPH, said in a statement.1
In addition, participants on Dovato had significantly less weight gain compared to those randomized to bictegravir/emtricitabine/tenofovir alafenamide.1
The trial met its primary endpoint with DTG/3TC demonstrating non-inferior efficacy compared to BIC/FTC/TAF.
Proportion of participants with weight gain greater than 5% was higher for BIC/FTC/TAF (29.9%) compared to DTG/3TC (20%).
The FDA approved Dovato for adolescents living with HIV earlier this year, making it the first and only oral, 2-drug, single-tablet regimen available for people aged 12 and older.
According to ViiV, the proportion of participants with weight gain greater than 5% at week 48 was significantly higher at 29.9% for bictegravir/emtricitabine/tenofovir alafenamide compared to 20% for dolutegravir/lamivudine (adjusted OR 1.81, 95% CI 1.19-2.76).1
“This is a meaningful outcome, as treatment-related weight gain is an important topic for many people living with HIV,” Garges said.1
Weight change with dolutegravir/lamivudine did not differ between men and women or based on the previous regimen of participants, whereas the proportion of trial participants experiencing greater than 5% weight gain with bictegravir/emtricitabine/tenofovir alafenamide was approximately 45% higher than those taking dolutegravir/lamivudine when switching from a regimen with abacavir (30.6% bictegravir/emtricitabine/tenofovir alafenamide vs 21.1% dolutegravir/lamivudine), and about 2-fold higher when switching from a regimen with TDF (40.7% bictegravir/emtricitabine/tenofovir alafenamide vs 19.5% dolutegravir/lamivudine).1
Earlier this year, the FDA approved Dovato for adolescents living with HIV. This therapy becomes the first and only oral, 2-drug, single-tablet regimen available for people aged 12 and older living with HIV.2
Dovato combines the integrase strand transfer inhibitor (INSTI) dolutegravir (50 mg) with the nucleoside reverse transcriptase inhibitor (NRTI) lamivudine (300 mg). INSTIs, like dolutegravir inhibit HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral DNA integration which is essential for the HIV replication cycle. The principal mode of action of lamivudine, an NRTIs, is inhibition of reverse transcriptase via DNA chain termination. 2
