Moderate inducers of CYP3A and P-gp, such as efavirenz, may significantly decrease plasma concentrations of lenacapavir, therefore co-administration is not recommended. Coadministration of lenacapavir (300 mg single oral dose) and efavirenz (600 mg once daily) decreased lenacapavir AUC and Cmax by 56% and 36%. If Sunlenca is discontinued, residual concentrations of lenacapavir may remain in the systemic circulation of patients for prolonged periods. These concentrations are not expected to affect the exposures of other antiretroviral agents that are initiated after discontinuation of Sunlenca.

Concomitant administration of efavirenz decreased lenacapavir concentrations and may result in loss of therapeutic effect and development of resistance. Concomitant administration with efavirenz is not recommended. Coadministration of lenacapavir (300 mg single oral dose) and efavirenz (600 mg once daily) decreased lenacapavir Cmax and AUC by 36% and 56%.