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Treatment of multi-drug resistant HIV-2 is an emerging issue, due to the rapid selection of mutations at time of virological failure and the low number of antiretrovirals active on HIV-2. The aim of this study was to determine the susceptibility of HIV-2 primary isolates to ibalizumab, a long-acting monoclonal antibody that binds to CD4, that is approved for the treatment of MDR HIV-1.In vitro phenotypic susceptibility of 16 HIV-2 primary isolates was measured using a modified version of the ANRS peripheral blood mononuclear cells (PBMC) assay. Susceptibility to ibalizumab was assessed through 50% inhibitory concentrations and maximum percent inhibitions (MPI), and gp105 was sequenced to look for determinants of reduced susceptibility.Ibalizumab inhibited viral replication of all 16 isolates, with a median IC50 value of 0.027 μg/mL (range = 0.001-0.506 μg/mL), and a median MPI of 93%. Although two isolates presented higher IC50 (above 0.1 μg/mL), they did not exhibit a loss of potential N-linked glycosylation sites in V5 loop, as reported in HIV-1 strains with reduced susceptibility. However, both presented shorter V1 and V2 loops than the HIV-2 reference strain.Ibalizumab inhibits HIV-2 replication, with IC50 and MPI in the range of those reported for HIV-1. These in vitro data support the use of ibalizumab in patients with MDR HIV-2, in combination with an optimized background regimen.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Citation

Quentin Le Hingrat, Gilles Collin, Antoine Bachelard, Jade Ghosn, Solayah Chalal, Jérôme Pacanowski, Gilles Peytavin, Steven Weinheimer, Christian Marsolais, Florence Damond, Sophie Matheron, Charlotte Charpentier, Diane Descamps, and the ANRS CO5 HIV-2 cohort. Ibalizumab shows in vitro activity against group A and group B HIV-2 clinical isolates. AIDS (London, England). 2022 Mar 08


PMID: 35262531

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