Switch to single-tablet bictegravir–lenacapavir from a complex HIV regimen (ARTISTRY-1): a randomised, open-label, phase 3 clinical trial

Background Single-tablet regimens (STRs) revolutionised HIV-1 treatment, improving adherence and clinical outcomes; however, many people cannot take these due to resistance, contraindications, or drug–drug interactions, instead relying on complex multi-tablet regimens. Novel STRs are therefore needed. We aimed to evaluate the efficacy and safety of a novel STR, bictegravir–lenacapavir, in people with HIV-1. Methods ARTISTRY-1 was a randomised, open-label, active-controlled, non-inferiority phase 3 trial conducted at hospitals and clinics across 15 countries that enrolled people with HIV-1 with virological suppression on complex regimens. Participants were randomly assigned (using interactive technology, 2:1, stratified by geographical region) to switch to once-daily oral bictegravir–lenacapavir 75 mg/50 mg STR or continued complex regimen. The primary outcome was the proportion of participants with an HIV-1 RNA viral load of 50 copies per mL or higher at week 48 (US Food and Drug Administration Snapshot algorithm), assessed in all randomly assigned participants who received any dose of assigned treatment. This trial (active; enrolment complete) was registered with ClinicalTrials.gov ( NCT05502341 ). Findings Between Jan 29 and Sept 26, 2024, 729 participants were screened; 557 were randomly assigned and treated (bictegravir–lenacapavir n=371; complex regimen n=186). At baseline, median age was 60 years (range 22–84), HIV treatment duration was 28 years (IQR 22–32); participants were taking a median of three antiretroviral pills per day (range 2–11). At week 48, an HIV-1 RNA viral load of 50 copies per mL or higher was observed in three (1%) participants receiving bictegravir–lenacapavir and two (1%) receiving a complex regimen (difference −0·3%; 95·002% CI −2·3 to 1·8), meeting the non-inferiority margin of 4%. No resistance emerged. Adverse event rates were similar between groups. Six (2%) participants discontinued bictegravir–lenacapavir and one (1%) discontinued their complex regimen due to adverse events. There were five deaths in the bictegravir–lenacapavir group, none of which were deemed related to study drug. Participants reported increased treatment satisfaction after switching to bictegravir–lenacapavir. Interpretation Bictegravir–lenacapavir STR demonstrated non-inferior efficacy to complex regimens, with a similar safety profile and increased treatment satisfaction. Bictegravir–lenacapavir offers new opportunities for HIV-1 treatment optimisation for people taking complex regimens. Funding Gilead Sciences.