Lenacapavir, a first-in-class inhibitor of HIV-1 capsid function, can be administered twice yearly subcutaneously (SC). In the ongoing Phase 2/3 CAPELLA study (NCT04150068), the addition of SC lenacapavir to an optimized background regimen led to high rates of virologic suppression and was generally well tolerated. We describe participant-reported, health-related quality-of-life (HRQoL) outcomes with lenacapavir among heavily treatment-experienced people with HIV (PWH) from CAPELLA. Scores from EQ-5D-5L index and visual analogue scale (VAS), Short Form 36 (SF-36), HIV-Symptom Index (HIV-SI), and Numeric Pain Rating Scale (NPRS) at injection were collected. Mean baseline and week (W) 52 scores were: EQ-5D-5L index, 0.87 and 0.83
EQ-5D-5L VAS, 81 and 86
SF-36 physical component, 48.5 and 49.9
SF-36 mental component, 48.4 and 48.0. Scores remained stable over time (<
7% change), with values near US norms. For 15 of 20 HIV-SI symptoms, fewer participants reported them as bothersome at W52 than at baseline. Mean NPRS scores on injection were 3.9, 5.1, and 4.4 at first (W0), second (W26), and third injection (W52). Participants on lenacapavir-based regimens demonstrated stability or improvement in HRQoL and other outcomes, with fewer participants reporting bothersome HIV symptoms. These data can help clinicians address individuals' needs and medication preferences while achieving sustained virologic suppression in heavily treatment-experienced PWH.