Lenacapavir-Containing Antiretroviral Therapy in the OPERA Cohort: Patterns of Use and Treatment Outcomes

Lenacapavir (LEN), a twice-yearly injectable long-acting capsid inhibitor used in combination with an optimized background regimen, is indicated for heavily treatment-experienced adults with multi-drug-resistant HIV-1 infection. From the US Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort, 116 adults with HIV with ≥1 set of LEN injections were included [baseline viral load (VL) <200 copies/mL = 74; ≥200 copies/mL = 42]. Many (56%) simplified their regimen at LEN initiation and/or later, and 31% maintained all the antiretrovirals (ARVs) from their prior regimen throughout LEN use. Among those with a baseline VL <200 copies/mL, the cumulative probability (Kaplan-Meier) of maintaining suppression to <200 copies/mL was 92% [95% confidence interval (CI): 80, 96]. Among those with a baseline VL ≥200 copies/mL, the cumulative probability of achieving suppression was 73% (95% CI: 59, 86). Among 78 individuals who received ≥2 sets of LEN injections, 82% received all sets of injections on time or early (≤28 weeks after the prior set) and 18% received ≥1 set late (>28 weeks after the prior set). The median delay was 11 days past the injection window (interquartile range: 4, 118). At study end, 91% remained on a LEN-containing regimen. In this cohort representative of routine clinical care in the United States, factors other than virologic control may be driving the decision to start LEN (e.g., safety, tolerability, resistance, simplification). Most people experienced favorable virologic outcomes and good adherence to LEN, which may serve as an effective option for those who could benefit from a long-acting injectable agent from a novel ARV class.