Background:
Lenacapavir (LEN), a potent first-in-class long-acting inhibitor of HIV-1 capsid function, is in development for treatment and prevention of HIV-1. CAPELLA is an ongoing Phase 2/3 study in people with HIV-1 (PWH) who are heavily treatment-experienced (HTE) and who are viremic on their current regimen with multidrug resistance (MDR). At Week 52, LEN in combination with an optimized background regimen (OBR) led to high rates of virologic suppression (78%, 56/72) and CD4 increase (median 84 cells/µL). We report subgroup analyses of Week 52 efficacy by baseline HIV-1 RNA, CD4, INSTI resistance, and OBR in both cohorts.
Methods:
The study included randomized and nonrandomized cohorts. In the randomized cohort, participants were randomized (2:1) to add oral LEN (600 mg on Days 1 and 2, 300 mg on Day 8) or placebo to their failing regimen. At Day 15 (D15), those on oral LEN received subcutaneous (SC) LEN 927 mg every 6 months (Q6M); those on placebo started the oral lead-in, followed by SC Q6M. Randomized participants discontinued the failing regimen and initiated an investigator-selected OBR at D15. In the nonrandomized cohort, participants initiated OBR concurrent with LEN (OBR concurrent with LEN oral lead-in). Week 52 efficacy was assessed in both cohorts using FDA snapshot algorithm.
Results:
72 participants enrolled (36 in each cohort). 46% (33/72) had 4-class resistance (NRTI, NNRTI, PI, and INSTI); 17% (12/72) had no fully active agents in the OBR. High rates of virologic suppression were achieved among participants who had baseline high HIV-1 RNA, low CD4, INSTI resistance, suboptimal OBR, and regardless of use of DTG and DRV in the OBR (Table).
Conclusions:
In this population of PWH who were heavily treatment-experienced with limited treatment options due to MDR HIV, LEN in combination with OBR led to high rates of virologic suppression, regardless of baseline HIV-1 RNA, CD4 count, INSTI resistance, and number of fully active OBR agents.
Table: HIV-1 RNA < 50 copies/mL at Week 52 (Snapshot Algorithm) by Subgroup