Background
Lenacapavir (LEN) is a potent first-in-class, long acting, capsid inhibitor recently approved for the treatment of multidrug-resistant HIV, in combination with other antiretroviral agents, in heavily treatment-experienced (HTE) people with HIV (PWH). PWH initiated usual or simplified regimen combining oral loading tablets and subcutaneous (SC) dose then SC maintenance dose (927 mg) every 6 months.
The objective of this analysis was to describe the plasma concentrations (Cpl) of LEN in HTE adults.
Methods
A multicenter, cross-sectional, cohort was conducted from 2020 to 2023. PWH who were receiving LEN containing regimen were enrolled. Basic demographic data were recorded using NADIS database (NCT#02898987). Blood samples were collected during the routine clinic visits between week 2, every each 6 months, and month 24 if available.
LEN Cpl were determined by UPLC-MSMS (Waters Acquity) with LOQ<5 ng/mL and interpreted using a cutoff of 15 ng/mL corresponding to 4-fold protein-adjusted 95% effective concentration on WT HIV-1. Results are presented as median (IQR).
Results
A total of 61 PWH (57% male; age 56 (43-60) years old) were enrolled. All were receiving LEN as an add-on to their antiretroviral regimen. Among them, 28 received both CAB long-acting intramuscular injection q8w with an associated daily oral antiretroviral backbone. A total of 191 LEN Cpl were measured in these PWH. Over all PWH, median (IQR) LEN Cpl were 50 (28-74) ng/mL with a number of samples per PWH of 2 (1-5). The intra-individual coefficient of variation was 30%, while the inter-individual variability was 69%. LEN Cpl were 44 (15-95) ng/mL, 28 (23-67) ng/mL, 45 (27-63) and 47 (29-73) ng/mL at W2, M1, M6, M6 and M12, respectively. Among our PWH, only one presented a LEN Cpl below the cutoff of 15 ng/mL. Of note, 5 patients presented LEN Cpl above 150 ng/mL, corresponding to PWH with acute or chronic kidney disease and/or receiving ritonavir-boosted atazanavir containing regimens. To date, no specific adverse events have been reported in these PWH, except some injection site reactions.
Conclusions
In our population of HTE HIV patients, PWH had adequate LEN Cpl. No drug-drug interaction was reported and tolerance of antiretroviral multitherapy was acceptable.
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