A French national real-world survey of people with multi-resistant HIV-1 viruses receiving an antiretroviral regimen including fostemsavir or ibalizumab

Abstract Background Attachment inhibitor fostemsavir (FTR) and post-attachment inhibitor ibalizumab (IBA), are used in highly treatment-experienced people with HIV-1 (PWH) harboring multidrug-resistant viruses, and real-world data remain limited. We describe population characteristics and pharmaco-virological outcomes of PWH initiating FTR- or IBA-based regimens. Methods We conducted a French retrospective observational study within the ANRS|MIE virology&pharmacology network. Virological failure (VF) was defined as two consecutive plasma viral loads (VL) ≥50 c/mL; non-virological response as a VL decrease <1 log10 c/mL or failure to achieve virological suppression. Results Among 70 PWH receiving FTR-based treatment, 50% were virologically-suppressed at initiation; median VL among viremic individuals was 3.6 log10 c/mL. Resistance to at least two ARVs was observed in 96%, 94%, 74%, and 64% of participants for NRTI, NNRTI, PI, and INSTI classes, respectively. Genotypic susceptibility score (GSS) was ≤1 in 47%, and median follow-up was 20 months. Eight VFs and eight non-virological responses occurred. At failure, emergence of FTR resistance-associated mutations occurred in one case. Suboptimal temsavir concentrations were observed in 2/8 participants in failure. Eleven viremic PWH initiated IBA-based treatment, GSS was ≤1 in four, and median follow-up was 7 months, with five VF and two non-virological responses. One new resistance mutation (N74D, capsid) was detected at VF; suboptimal plasma concentrations of oral ARV were observed in 3/5 participants. Conclusions PWH receiving FTR or IBA had extensive multidrug-resistance and limited therapeutic options. Virological success was achieved in 63% and 36% of viremic PWH initiating FTR- and IBA-based regimens, respectively, and maintained in 91% of virologically-suppressed PWH starting FTR-based regimen.