Oxford Academic: Resistance Analyses of Lenacapavir, Emtricitabine/Tenofovir Alafenamide and Emtricitabine/Tenofovir Disoproxil Fumarate in the PURPOSE 1 and 2 Studies
Background
Lenacapavir (LEN) is an HIV-1 capsid inhibitor being studied for pre-exposure prophylaxis (PrEP). The PURPOSE 1 and PURPOSE 2 trials evaluated LEN’s effectiveness compared to emtricitabine/tenofovir disoproxil fumarate (F/TDF), and also emtricitabine/tenofovir alafenamide (F/TAF) in cisgender women (P1). PURPOSE 2 included cisgender men, transgender individuals, and nonbinary persons. LEN showed superior efficacy over F/TDF in both studies. This report presents resistance data from both trials, marking the first insights into drug resistance related to LEN in a PrEP context.
Methods
HIV testing was conducted at screening, baseline, and each study visit. Participants who acquired HIV with a viral load ≥200 copies/mL were tested for resistance mutations in HIV-1 capsid, protease, reverse transcriptase, and integrase genes. Adherence to F/TDF and F/TAF was monitored via dried blood spot analysis.
Results
- No LEN resistance was found in P1 (0/2134 participants).
- In P2, 2 out of 2179 participants developed LEN resistance (N74D mutation).
- Eight participants had undiagnosed HIV at baseline; 4 of these developed the N74D mutation.
- In P1, 2 out of 37 participants on F/TAF had M184I and K65R mutations.
- In the F/TDF groups, M184M/I/V mutations were found in 1/16 (P1) and 1/9 (P2) participants.
Conclusions
HIV acquisition while on LEN was rare. However, when it occurred in individuals with undiagnosed HIV, it was associated with the emergence of the N74D mutation, indicating LEN resistance.