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

Background: There is a continued need to expand the repertoire of effective single-tablet regimens to address the diverse needs of people with HIV-1. We aimed to evaluate the safety and efficacy of switching to bictegravir-lenacapavir compared with continuing bictegravir-emtricitabine-tenofovir alafenamide in virologically suppressed people with HIV-1. Methods: This double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial was conducted in 100 hospitals and HIV clinics across Argentina, Australia, Canada, 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, receiving bictegravir-emtricitabine-tenofovir alafenamide (for ≥6 months), and virologically suppressed (HIV-1 RNA <50 copies per mL for ≥6 months). Participants were randomly assigned (2:1) using an interactive response system (stratified by geographical region) to switch to bictegravir-lenacapavir (75-50 mg) or continue bictegravir-emtricitabine-tenofovir alafenamide (50-200-25 mg) once a day as single-tablet regimens for 48 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA of 50 copies per mL or higher at week 48 (as per the US Food and Drug Administration Snapshot algorithm) assessed in the full analysis set (defined as all randomly assigned participants who received any dose of the study drug), with a non-inferiority margin of 4%. This trial is registered with ClinicalTrials.gov, NCT06333808 (active, not recruiting). Findings: Between March 25 and Oct 30, 2024, 666 people with HIV-1 were assessed for eligibility, 89 were ineligible, and 577 were randomly assigned (384 to bictegravir-lenacapavir and 193 to continue bictegravir-emtricitabine-tenofovir alafenamide). 574 participants received at least one dose of the study drug (full analysis set). The median age was 49 years (IQR 39-58). 111 (19%) of 574 participants were female and 463 (81%) were male at birth. At baseline, the median duration of HIV-1 treatment was 12·0 years (6·5-18·7). At week 48, five (1·3%) of 383 participants in the bictegravir-lenacapavir group and two (1·0%) of 191 in the bictegravir-emtricitabine-tenofovir alafenamide group had HIV-1 RNA of 50 copies per mL or higher (percentage difference 0·3% [95·002% CI -1·9 to 2·4]), meeting the non-inferiority criteria. Drug-related adverse events occurred in 40 (10%) participants in the bictegravir-lenacapavir group versus 23 (12%) in the bictegravir-emtricitabine-tenofovir alafenamide group; and serious adverse events occurred in 27 (7%) versus 13 (7%), with none deemed related to treatment. One participant in the bictegravir-emtricitabine-tenofovir alafenamide group died due to coronary artery disease. Interpretation: Bictegravir-lenacapavir has the potential to be a novel single-tablet antiretroviral regimen option for virologically suppressed people with HIV-1. Funding: Gilead Sciences.