Research Summary

Bictegravir–Lenacapavir Switch Maintains Viral Suppression in HIV-1, Phase 3 Trial Finds

Edited by:
Ashton L. Stahl

Key Highlights

  • Bictegravir–lenacapavir met noninferiority criteria vs continued bictegravir–emtricitabine–tenofovir alafenamide at week 48.
  • The phase 3 ARTISTRY-2 trial included 574 treated participants with virologically suppressed HIV-1.
  • HIV-1 RNA of 50 copies/mL or higher occurred in 1.3% vs 1.0% of participants, respectively.
  • Drug-related adverse events and serious adverse events were similar between treatment groups.

Switching to once-daily bictegravir–lenacapavir was noninferior to continuing bictegravir–emtricitabine–tenofovir alafenamide for maintaining viral suppression in adults with HIV-1, according to findings from the phase 3 ARTISTRY-2 trial published in The Lancet HIV. The study was designed to assess the safety and efficacy of a novel single-tablet antiretroviral regimen in people who were already virologically suppressed while receiving bictegravir–emtricitabine–tenofovir alafenamide.

Researchers conducted a double-blind, multicenter, randomized, controlled, phase 3 noninferiority trial across 100 hospitals and HIV clinics in Argentina, Australia, Canada, the Dominican Republic, Germany, Italy, Japan, Mexico, Puerto Rico, South Korea, Spain, Taiwan, the UK, and the USA. Eligible participants were aged 18 years or older, had received bictegravir–emtricitabine–tenofovir alafenamide for at least 6 months, and had HIV-1 RNA below 50 copies/mL for at least 6 months. Participants were randomly assigned 2:1 to switch to bictegravir–lenacapavir 75–50 mg or continue bictegravir–emtricitabine–tenofovir alafenamide 50–200–25 mg once daily as single-tablet regimens for 48 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA of 50 copies/mL or higher at week 48, assessed using the FDA Snapshot algorithm, with a noninferiority margin of 4%.

Study Findings

Between March 25 and October 30, 2024, 666 people with HIV-1 were assessed for eligibility. Of these, 89 were ineligible, and 577 were randomly assigned, including 384 to bictegravir–lenacapavir and 193 to continued bictegravir–emtricitabine–tenofovir alafenamide. The full analysis set included 574 participants who received at least 1 dose of the study drug.

The median participant age was 49 years, with an IQR of 39 to 58 years. Of the 574 participants, 111 (19%) were female, and 463 (81%) were male at birth. At baseline, the median duration of HIV-1 treatment was 12 years.

At week 48, HIV-1 RNA of 50 copies/mL or higher occurred in 5 of 383 participants (1.3%) in the bictegravir–lenacapavir group and 2 of 191 participants (1%) in the bictegravir–emtricitabine–tenofovir alafenamide group. The percentage difference was 0.3% (95.002% CI, –1.9 to 2.4), meeting the prespecified noninferiority criteria.

Safety outcomes were comparable between groups. Drug-related adverse events occurred in 40 participants (10%) in the bictegravir–lenacapavir group and 23 participants (12%) in the bictegravir–emtricitabine–tenofovir alafenamide group. Serious adverse events occurred in 27 participants (7%) and 13 participants (7%), respectively, and none were deemed related to treatment. One participant in the bictegravir–emtricitabine–tenofovir alafenamide group died due to coronary artery disease.

Clinical Implications

According to the study authors, the findings suggest that bictegravir–lenacapavir could expand the repertoire of effective single-tablet antiretroviral regimen options for virologically suppressed people with HIV-1.

Expert Commentary

“Bictegravir–lenacapavir has the potential to be a novel single-tablet antiretroviral regimen option for virologically suppressed people with HIV-1,” the researchers concluded.

Reference

Meissner EG, Ramgopal M, Ruane PJ, Sanchez W, Crofoot G, Routy JP, et al. Safety and efficacy of switching to bictegravir-lenacapavir versus continuing bictegravir-emtricitabine-tenofovir alafenamide in virologically suppressed people with HIV-1 (ARTISTRY-2): a double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet HIV. Published online 2026. doi:10.1016/S2352-3018(26)00078-0