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The two-drug regimen dolutegravir/lamivudine (DTG/3TC; Dovato) was just as effective as the three-drug regimen bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF; Biktarvy) for maintaining viral suppression in people with HIV, according to the Spanish phase IV PASO-DOBLE trial.

At 48 weeks, 2.2% of patients who switched from their previous antiretroviral therapy (ART) to a DTG/3TC regimen had a viral load of HIV-1 RNA ≥50 copies/mL versus 0.7% who switched to BIC/FTC/TAF, for a risk difference of 1.4% (95% CI -0.5 to 3.4), reported Esteban Martinez, MD, PhD, of the University of Barcelona, at the International AIDS Conference in Munich.

None of the participants in the DTG/3TC arm and one participant in the BIC/FTC/TAF arm had confirmed virological failure through week 48, defined as HIV-1 RNA ≥50 copies/mL followed by a second consecutive HIV-1 RNA assessment of ≥200 copies/mL. There was no emergent resistance in either treatment group, nor any significant differences in CD4 counts, between the groups over the 48-week follow-up, Martinez said.

"As HIV requires lifelong therapy, optimizing ART in the setting of viral suppression is needed," Martinez told attendees. "DTG/3TC and BIC/FTC/TAF are preferred regimens in major guidelines, but there are no fully powered trials comparing between them."

A key secondary endpoint of the study focused on the effects of each regimen on weight change. Participants in the BIC/FTC/TAF arm gained a mean 1.81 kg from baseline, whereas those who switched to the DTG/3TC arm gained a mean 0.89 kg, for a mean adjusted difference of 0.92 kg (95% CI 0.17-1.66) through week 48.

The percentage of participants with weight gain greater than 5% at week 48 was significantly higher at 29.9% for the BIC/FTC/TAF group versus 20% for the DTG/3TC group (adjusted OR 1.81, 95% CI 1.19-2.76, P=0.006).

Although weight gain after initiation of ART has been associated with a in underweight or normal-weight patients with HIV, other studies suggest that weight gain in the setting of ART may lead to obesity and , especially in people with HIV as they age.

When analyzing body mass index (BMI) by visit, the researchers found no change in the proportion of participants taking DTG/3TC who had obesity at week 48 versus at baseline. However, in the BIC/FTC/TAF arm, the proportion of participants with obesity increased over time, from 18% at baseline to 21% at week 48.

Previous ART regimens with nucleoside reverse transcriptase inhibitor (NRTI) 1 drugs affected the amount of weight gain with BIC/FTC/TAF, but not with DTG/3TC. When switching from a prior regimen with abacavir (Ziagen), 30.6% of participants in the BIC/FTC/TAF arm had greater than 5% weight gain versus 21.1% of those in the DTG/3TC arm, a difference of about 45%, Martinez pointed out.

The difference was about twofold higher in the BIC/FTC/TAF arm when switching from a regimen with tenofovir disoproxil fumarate (TDF): 40.7% versus 19.5% in the DTG/3TC arm.

There were no specific patterns of weight gain associated with NRTI 2 agents or core drugs, Martinez noted.

Adverse events were generally similar between the two groups, although there was a trend toward a significantly higher percentage of grade 3-4 adverse events in the BIC/FTC/TAF arm versus the DTG/3TC group (3.6% vs 1.1%, P=0.049). However, these were not related to treatment, according to Martinez.

Only three participants discontinued treatment, one in the DTG/3TC arm due to general discomfort and arthromyalgia and two in the BIC/FTC/TAF arm due to sleep disturbances.

The open-label, randomized clinical trial is being conducted at 30 sites across Spain. Virologically suppressed people with HIV were eligible to enroll in the study if their current ART regimen contained one or more pills per day, boosters, or drugs with cumulative toxicity, such as efavirenz (Sustiva) or TDF, and if they had no prior virologic failure or resistance, no chronic hepatitis B, and no prior use of DTG or BIC.

A total of 553 participants were randomized 1:1 to switch from their prior regimen to either DTG/3TC (n=277) or BIC/FTC/TAF (n=276). Mean age was about 50 years, approximately 25% were non-Caucasian, and 26% were female at birth. Participants had been on their prior ART regimen for a mean duration of 63 to 66 months, and on any ART for 11 to 12 years. Approximately 50% had overweight or obesity (BMI >25) at baseline. A further analysis of data is planned at 96 weeks of follow-up.

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