A study in 30 Spanish hospitals shows that a two-drug HIV therapy remains more effective than a three-drug one.

Dolutegravir/lamivudine demonstrated non-inferiority to bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) in HIV-infected adults with suppressed viral load. SEIMC-GeSIDA Foundation and ViiV Healthcare today announce positive 48-week results from the PASO DOBLE study (GeSIDA study 11720), the largest randomized phase IV clinical trial comparing the two-drug Dovato (dolutegravir/lamivudine (DTG/3TC)) with the three-drug Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF)) for the treatment of HIV-1 in people with suppressed viral load.

The study showed that switching to dual-drug DTG/3TC therapy in HIV-infected adults with suppressed viral load is as effective as switching to triple-drug BIC/FTC/TAF therapy in maintaining virologic suppression. The findings were presented at the 25th International AIDS Conference (AIDS 2024), which is taking place in Munich, Germany, from 22 to 26 July.

553 people with HIV from 30 Spanish centres

The randomized clinical trial PASO DOBLE (NCT04884139) is an open-label, randomized, multicenter, phase IV clinical trial involving 30 hospitals from ten Spanish provinces.

553 HIV-infected individuals with suppressed viral load were randomized to receive DTG/3TC (n=277) or BIC/FTC/TAF (n=276). Enrollees had not previously received either drug and had received a multiple-pill or single-pill regimen containing at least one of the following drugs within the previous 24 weeks: cobicistat as a booster, efavirenz, or tenofovir disoproxil fumarate).

Efficiency

The study met its primary objective when DTG/3TC demonstrated non-inferiority to BIC/FTC/TAF (based on the percentage of participants with HIV-1 RNA greater than or equal to 50 copies/mL at 48 weeks, according to a snapshot analysis (FDA non-inferiority margin of 4% in the intent-to-treat population). At 48 weeks, DTG/3TC was non-inferior to BIC/FTC/TAF (the risk difference between DTG/3TC (2.2%) minus BIC/FTC/TAF (0.7%) was 1.4%, 95% CI -0.5 to 3.4.

Less weight gain

The study also found that weight gain was significantly greater in participants who switched to the three-drug regimen (adjusted mean 1.81 kg, 95% CI: 1.28-2.34) than in those who switched to the two-drug regimen (adjusted mean 0.89 kg, 95% CI: 0.37-1.41) (adjusted mean difference 0.92 kg, 95% CI: 0.17-1.66). Similarly, the proportion of participants who gained more than 5% of their weight at week 48 was significantly higher with BIC/FTC/TAF than with DTG/3TC (29.9% vs 20.0%, respectively, adjusted OR 95% CI: 1.81 (1.19-2.76) )

Weight change with DTG/3TC did not differ between men and women or by participants’ prior treatment regimen, while the proportion of study participants who experienced a weight gain of more than 5% with BIC/FTC/TAF was approximately 50% higher than in those on DTG/3TC when switching from abacavir and approximately twice as high when switching from tenofovir. There were a few discontinuations due to adverse events in both study arms (DTG/3TC = 1, 0.4%; BIC/FTC/TAF = 2, 0.7%), with no differences between groups.

Esteban Martínez, principal investigator of the PASO DOBLE study and senior consultant in infectious diseases at the Clínic Hospital de Barcelona, ​​says: “All the antiretroviral drugs prescribed today to treat HIV are very effective, so it is essential that we study the impact of these treatments beyond viral suppression. “The results of DOUBLE STEP show that Dovato not only maintained the same efficacy as the three-drug regimen, but also showed significantly less weight gain over 48 weeks.”