Karl Stefic, Camille Tumiotto, Anne de Monte, Marc Wirden, Audrey Rodallec, Djeneba Fofana, Marie-Laure Chaix, Pantxika Bellecave, Elisabeth Garnier, Justine Sourice, Camille Vellas, Stéphanie Raymond, Sidonie Lambert-Niclot, Enagnon Kazali Alidjinou, Pauline Coulon, Véronique Avettand-Fenoel, Gilbert Mchantaf, Lynda Handala, Elodie Alessandri-Gradt, Alice Moisan, Minh Lê, Constance Delaugerre, Anne-Geneviève Marcelin, Gilles Peytavin, Vincent Calvez, Diane Descamps, Charlotte Charpentier, Entry Inhibitors Observatory Study Group, Entry Inhibitors Observatory Study Group
PWH receiving FTR or IBA had extensive multidrug resistance and limited therapeutic options. Among PWH who were viremic and initiating FTR- and IBA-based regimens, virologic success was achieved in 63% and 36%, respectively, and maintained in 91% who were virologically suppressed and starting an FTR-based regimen.
BACKGROUND: Attachment inhibitor fostemsavir (FTR) and postattachment inhibitor ibalizumab (IBA) are used in people with HIV-1 (PWH) who are highly treatment experienced and harboring multidrug-resistant viruses, and real-world data remain limited. We describe population characteristics and pharmacovirologic outcomes of PWH initiating FTR- or IBA-based regimens.
METHODS: We conducted a French retrospective observational study within the AIDS Research National Agency | Emerging Infectious Diseases virology and pharmacology network. Virologic failure (VF) was defined as 2 consecutive plasma viral loads (VLs) ≥50 copies/mL; nonvirologic response was considered a VL decrease <1 log10 copies/mL or failure to achieve virologic suppression.
RESULTS: Among 70 PWH receiving FTR-based treatment, 50% were virologically suppressed at initiation; median VL among viremic cases was 3.6 log10 copies/mL. Resistance to at least 2 antiretrovirals was observed among participants by inhibitor class: 96%, nucleoside reverse transcriptase inhibitor; 94%, nonnucleoside reverse transcriptase inhibitor; 74%, protease inhibitor; and 64%, integrase strand transfer inhibitor. The genotypic susceptibility score was ≤1 in 47%, and median follow-up was 20 months. Eight VFs and 8 nonvirologic responses occurred. At failure, emergence of FTR resistance-associated mutations occurred in 1 case. Suboptimal temsavir concentrations were observed in 2 of 8 participants in failure. Eleven PWH who were viremic initiated IBA-based treatment: the genotypic susceptibility score was ≤1 in 4, and median follow-up was 7 months with 5 VFs and 2 nonvirologic responses. One new resistance mutation (N74D, capsid) was detected at VF; suboptimal plasma concentrations of oral antiretrovirals were observed in 3 of 5 participants.
CONCLUSIONS: PWH receiving FTR or IBA had extensive multidrug resistance and limited therapeutic options. Among PWH who were viremic and initiating FTR- and IBA-based regimens, virologic success was achieved in 63% and 36%, respectively, and maintained in 91% who were virologically suppressed and starting an FTR-based regimen.