Less weight gain with Dovato than Biktarvy

Switching to a two-drug regimen of dolutegravir / lamivudine (Dovato) resulted in significantly less weight gain after 96 weeks compared to a switch to tenofovir alafenamide / emtricitabine / bictegravir (Biktarvy), the final results of a large, randomised trial conducted in Spain have shown.

Dr Esteban Martinez of the Hospital Clinic Barcelona presented 96-week results of the PASO-DOBLE study last week at the 20th European AIDS Conference (EACS 2025) in Paris.

Some studies have ruled out any contribution of antiretroviral drug type to weight gain after starting or switching treatment. However, Professor Dominique Costagliola argued in a session on weight gain that studies consistently show a greater effect on weight associated with treatment containing tenofovir alafenamide (TAF), bictegravir or dolutegravir.

The PASO-DOBLE study was designed to compare the virologic efficacy and changes in weight in people with suppressed viral load who switched from a regimen containing efavirenz, tenofovir or a cobicistat-boosted agent to maintenance treatment with either Dovato or Biktarvy. The study excluded people with any prior experience of taking dolutegravir or bictegravir.

PASO-DOBLE randomised 543 people with HIV to either Dovato (n=277) or Biktarvy (n=276). Participants had a median age of 50 years, just under three-quarters were female and they had been taking antiretroviral treatment for a median of 11 years. At the time of study entry, participants had been taking their current regimen for a median of five years.

The 48-week primary analysis of PASO-DOBLE, first presented at AIDS 2024 and subsequently published in The Lancet HIV showed that two-drug treatment was virologically non-inferior to three-drug treatment as a maintenance regimen. At week 96, 1.1% of the Biktarvy group and 0.4% of the Dovato group had viral load above 50 copies/ml, the primary study outcome. A slightly higher proportion of those in the Dovato arm had viral load below 50 copies (90.3% vs 85.9%). However, neither of these differences were statistically significant.

In the Dovato group, there were no cases of confirmed virologic failure where viral load rose above 200 copies/ml after an initial measurement above 50 copies/ml. In the Biktarvy group, there were three cases. None of these resulted in the development of new resistance mutations.

There were similar rates of adverse events and serious adverse events in the study arms, but the rate of drug-related adverse events was significantly higher in the Biktarvy arm (13.4% vs 7.6%). However, the rate of study withdrawal due to adverse events did not differ significantly between the study arms (1.4% vs 0.7%).

The key secondary endpoint was weight change. At week 48, participants in the Biktarvy arm had gained significantly more weight than those in the dolutegravir arm (mean adjusted difference +1.13kg) and this difference increased by week 96 (adjusted difference +1.52kg).

Not only did they gain more weight but the proportion who gained at least 5% in body weight by week 96 was significantly higher in the Biktarvy arm (37.8% vs 24.01%). Participants in this arm were twice as likely to have gained this amount of weight by week 96 compared to the Dovato arm (odds ratio 2.02, p=0.001).

Weight gain of at least 5% by week 96 was independently associated with Biktarvy treatment compared to Dovato treatment in multivariate analysis (adjusted odds ratio 1.92).

The analysis also looked at whether the presence of weight-suppressive antiretrovirals in the previous regimen increased the odds of substantial weight gain after switching. The presence of tenofovir disoproxil fumarate (TDF) without efavirenz in the previous regimen was associated with 88% increased odds of >5% weight gain (aOR 1.88), while the presence of TDF with efavirenz raised the risk of >5% weight gain by 78% (aOR 1.78). However, the presence of efavirenz in the previous regimen did not significantly increase the risk of >5% weight gain, despite its association with weight suppression in previous studies.

There were significant differences in absolute changes in metabolic parameters between those who gained at least 5% in body weight and those who gained less weight by week 96. The most substantial difference was in triglyceride levels; those who gained less than 5% in weight experienced a mean reduction of 31.8mg/dl by week 96, whereas those who gained at least 5% in weight experienced a mean increase of 13.6mg/dl by week 96 (p<0.001). Participants who gained less than 5% in weight also experienced modest reductions in total cholesterol, LDL cholesterol and insulin, whereas those who gained at least 5% in body weight experienced modest increases in these parameters. HDL cholesterol levels improved slightly in those who gained less weight and fell slightly in those who gained at least 5% in body weight.