TOPLINE:

In a phase 4 study, switching to dolutegravir/lamivudine was noninferior in virological efficacy than switching to bictegravir/emtricitabine/tenofovir alafenamide at 48 weeks with very few treatment discontinuations due to adverse events in adults with HIV who had achieved virological suppression. However, bictegravir based regimen was associated with a greater weight gain.

METHODOLOGY:

• Researchers conducted a phase 4, noninferiority trial (PASO-DOBLE) to compare the efficacy and safety of dolutegravir/lamivudine with bictegravir/emtricitabine/tenofovir alafenamide as maintenance therapy for people with HIV.
• They enrolled 556 participants with HIV-1 infection (median age, 50 years; 73% men) who had achieved virological suppression with oral regimens containing at least one pill daily and those who had no previous use of dolutegravir or bictegravir.
• Participants were randomly assigned to switch their regimen to once daily of either dolutegravir/lamivudine or bictegravir/emtricitabine/tenofovir alafenamide.
• The primary endpoint was the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at week 48 and key secondary endpoints were change in weight, fasting glucose, A1c levels, fibrosis-4 scores, and homeostatic model assessment for insulin resistance (HOMA-IR) values.

TAKEAWAY:

• At 48 weeks, dolutegravir/lamivudine regimen was noninferior to bictegravir/emtricitabine/tenofovir alafenamide regimen. The difference in viral suppression, measured by the proportion of participants with HIV-1 RNA ≥ 50 copies/mL, stood at 1.4% (95% CI, -0.5 to 3.4; P = .16), meeting the trial’s noninferiority threshold.
• Weight gain was significantly greater in participants on the bictegravir regimen than those on the dolutegravir regimen, with a difference in mean weight change of 0.92 kg (P = .016).
• Grade 3-4 adverse events were also higher in the bictegravir group than in the dolutegravir group (3% vs 1%; P = .049). Three participants discontinued treatment due to adverse events; one in dolutegravir group (general discomfort with arthromyalgia) and two in bictegravir group (insomnia and sleep disturbances).
• No significant changes were observed in fasting glucose, A1c levels, HOMA-IR values, and fibrosis-4 scores within or between groups.

IN PRACTICE:

“The PASO-DOBLE trial provides important evidence for HIV practitioners and researchers by showing that dolutegravir and lamivudine — a key option for antiretroviral regimen optimization in people with HIV at risk of obesity — offers a modest but favorable impact on weight gain trajectories with noninferior virological efficacy,” the authors of a linked commentary wrote.

SOURCE:

This study was led by Pablo Ryan, PhD, Hospital Universitario Infanta Leonor, Madrid, Spain, and José L. Blanco, PhD, Hospital Clínic de Barcelona, Barcelona, Spain. It was published online on June 6, 2025, in The Lancet HIV.

LIMITATIONS:

Dolutegravir and lamivudine regimen was not recommended for pregnant women or people with hepatitis B, leading to their exclusion from the study. The open-label design potentially introduced bias due to the lack of masking for participants and investigators. The study population also lacked diversity, with limited representation of certain racial and ethnic groups, particularly Black or African individuals.

DISCLOSURES:

This study received funding from ViiV Healthcare, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, and Institut d’Investigacions Biomèdiques August Pi i Sunyer. One author reported being an employee of ViiV Healthcare and owning stocks or stock options in the company. Several other authors reported receiving financial support from various organizations and pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.