The following is a summary of “Resistance Analyses in Highly Treatment-Experienced People With Human Immunodeficiency Virus (HIV) Treated With the Novel Capsid HIV Inhibitor Lenacapavir,” published in the 1 December 2022 issue of Infectious Diseases by Margot, et al.

Lenacapavir (LEN), a first-in-class inhibitor of the human immunodeficiency virus type 1 (HIV-1) capsid function, was being tested in humans for the treatment of heavily treatment-experienced (HTE) people with HIV (PWH) who are harboring MDR in conjunction with an improved background regimen (OBR). For a study, researchers sought to discuss the resistance analyses that were carried out for the crucial phase 2/3 CAPELLA trial.

Viremic HTE PWH with resistance to ≥2 ARVs per class and to ≥3 of the 4 major antiretroviral (ARV) classes were included in the CAPELLA study. Commercial assays were utilized for baseline resistance assessments (integrase genotypic/phenotypic testing, reverse transcriptase, and HIV-1 protease). Participants virologically failing were examined for postbaseline resistance.

At the outset, 46% of participants had developed resistance to at least ≥3 of the 4 main classes of ARV medications, and 33% had used up all available medication from those classes. 81% of subjects experienced viral suppression after receiving LEN + OBR treatment for 26 weeks. Eight patients (6 with M66I, 1 with K70H, and 1 with Q67H + K70R) who were receiving unexpected functional LEN monotherapy at the time of resistance selection had postbaseline resistance mutations to lenacapavir.

In the HTE patient group with MDR, LEN added to OBR resulted in good effectiveness, but it might select for resistance when administered accidentally as functional monotherapy.