Abstract
BACKGROUND: Lenacapavir is a twice-yearly HIV-1 capsid inhibitor approved, in combination with other antiretrovirals, for the treatment of heavily treatment-experienced people with multidrug-resistant HIV, based on the Phase 2/3 CAPELLA study. Here, we report week 156 efficacy and safety results. METHODS: In CAPELLA (NCT04150068), participants received 2-week oral lenacapavir lead-in doses, followed by subcutaneous lenacapavir every 6 months, combined with an investigator-selected optimized background regimen. Endpoints included virologic outcomes, CD4 cell count trends, adverse events, and treatment-emergent resistance. RESULTS: CAPELLA enrolled 72 participants: 25% female; 38% Black; median age, 52 years; CD4 cell count <200 cells/μL, 64% (<50 cells/μL, 22%). At week 156, 61% (43/70) had HIV RNA <50 copies/mL by FDA Snapshot Algorithm, 16% (11/70) had ≥50 copies/mL, and 23% (16/70) had missing data; by missing = excluded analysis, 85% (44/52) had HIV RNA <50 copies/mL. Mean CD4 cell count increase from baseline to week 156 was 164 cells/μL (95% CI: 116-211). Through week 156, 14/72 participants developed emergent LEN resistance. Injection site reactions were mostly Grade 1/2, and frequency declined over time. Through week 156, two participants discontinued lenacapavir due to Grade 1 injection site nodules. CONCLUSIONS: Lenacapavir plus an optimized background antiretroviral regimen maintained a high rate of virologic suppression at week 156 with continued increases in CD4 counts. Lenacapavir was well tolerated with a favorable safety profile and very low rates of lenacapavir discontinuation. These data demonstrate longer-term efficacy and safety of lenacapavir for heavily treatment-experienced people with multidrug-resistant HIV.