Abstract Background Lenacapavir (LEN) with an optimized background regimen (OBR) was evaluated in a French cohort of multidrug-resistant HIV participants via compassionate use. Methods Adults (n=42) with HIV-1 (PLWH1, n=33) or HIV-2 (PLWH2, n=9), receiving at least one dose of LEN plus OBR, were prospectively followed between January 2021 and December 2023. The primary endpoint was virological suppression (plasma HIV-1 RNA (VL) 50 copies/mL at week 26 (W26), using FDA Snapshot algorithm. Secondary endpoints included long-term VL, resistance emergence, LEN plasma concentration, and drug safety. Results At baseline, PLWH1 presented a median VL of 4.0 log10 copies/mL with 14/33 (42%) having VL below 50 copies/ml, while PLWH2 had 3.0 log10 copies/mL (with baseline VL50 copies/mL for 3). By W26, virological suppression was achieved or maintained in 67.0% (95% CI 48.2–82.0) of PLWH1, with a mean CD4+ increase of +86 cells/μL. In PLWH2, virological suppression occurred in only 22.0% (95% CI 2.8–60.0), with CD4+ counts rising by +27 cells/μL. Emergence of LEN resistance was documented in one PLWH1 (Q67H) and three PLWH2 (all N73D). The median LEN plasma concentration was 43 ng/mL after 26 weeks of subcutaneous injections. Tolerance was acceptable with 31% reported injection site reactions leading to discontinuation in two patients, and no grade 3/4 treatment-related adverse events occurred (two deaths unrelated to treatment). Conclusion LEN plus OBR showed robust efficacy and safety in PLWH1 but limited antiviral activity in PLWH2 due to limited OBR. These findings support LEN as an effective option in highly treatment-experienced PLWH1, while underscoring challenges for PLWH2.
Delaugerre et al. (Wed,) studied this question.