BACKGROUND: Lenacapavir (LEN) is a first-in-class, long-acting, HIV-1 capsid inhibitor, recently approved, in combination with other antiretrovirals, for treatment of multidrug-resistant (MDR) HIV-1. Subcutaneous (SC) LEN provides a Q6M treatment option for HIV-1; however, potential SC treatment interruptions may lead to management challenges due to SC treatment gaps. This subanalysis investigated the efficacy and safety of an oral bridging (OB) regimen (LEN 300 mg PO QW) in participants with MDR HIV-1 as well as treatment-naïve people with HIV-1 (PWH) enrolled in the CAPELLA and CALIBRATE studies, respectively, when SC LEN dosing was interrupted due to its clinical hold.
METHODS: Virologic suppression, CD4+ cell counts, and safety outcomes were assessed from available data at baseline (time of initiation of OB) and until SC resumption or early discontinuation from OB due to FDA clinical hold (12/2021–05/2022).
RESULTS: Of 72 participants who received SC LEN in CAPELLA, 57 received OB (79%) and were included in this analysis. Of 105 participants who received SC LEN in CALIBRATE, 82 received OB (78%). In both studies, demographic and baseline characteristics were similar between OB and overall analysis sets. Median OB exposure was 19 weeks, and OB adherence (by pill count) was =95% in most participants. Results were consistent across both subanalyses. High virologic suppression rates were maintained among those already suppressed (HIV-1 RNA <50 copies/mL) at OB baseline in CAPELLA and in all participants in CALIBRATE (Table). CD4 (abs/%) remained stable or increased from OB baseline. One participant (CAPELLA) who missed 2 non-consecutive oral LEN doses did not maintain virologic suppression during OB. Treatment-emergent AEs were similar to SC LEN. Two participants in CAPELLA (3.5%) and 1 participant in CALIBRATE (1.2%) experienced treatment-related diarrhea.

Table: Number and Proportion of Participants With HIV-1 RNA < 50 copies/mL by Visit, Missing = Excluded
OB Baseline46/46 (100)82/82 (100)
OB Week 1044/45 (98)77/77 (100)
OB Week 2030/31 (97)58/58 (100)
OB Week 30 10/10 (100)5/5 (100)
aParticipants had virologic suppression at OB Baseline bDenominators reflect participants who reached the specified duration of OB.

CONCLUSIONS: High rates of virologic suppression, and stable or increased CD4, support efficacy of OB in PWH, including those with MDR HIV-1 whose SC LEN treatment was interrupted. During OB, LEN was generally safe and well tolerated.