A precautionary tale of lenacapavir drug-drug interactions: A case series of two persons living with HIV receiving long-acting injections

Lenacapavir is now approved for highly treatment experienced persons living with HIV (PLWH) and for HIV pre-exposure prophylaxis (PrEP). Limited lenacapavir clinical data exist with real-world drug-drug interactions. We report two possible drug-drug interactions with ambulatory lenacapavir subcutaneous injections in two PLWH prescribed long-acting injection therapy. Case 1 describes a PLWH prescribed clopidogrel after an acute cerebrovascular event receiving an antiretroviral (ARV) regimen including subcutaneous lenacapavir and ibalizumab biweekly infusions. The clopidogrel was discontinued with no harm noted. Case 2 is a highly treatment experienced PLWH prescribed an ARV regimen including subcutaneous lenacapavir and intramuscular cabotegravir/rilpivirine injections on concomitant inhaled and nasal fluticasone. Symptoms consistent with adrenal insufficiency were reported with immediate fluticasone discontinuation and transition to beclomethasone. The patient's baseline cortisol concentration was low with improvement after fluticasone discontinuation. The electronic medical record alerts were customized to note these possible lenacapavir drug-drug interactions, similar to protease inhibitors/pharmacokinetic boosters (ritonavir and cobicistat) to prevent future events. This case series highlights possible lenacapavir drug-drug interactions and is a precautionary tale to other institutions to consider customizing electronic medical alerts for this novel long-acting injection.