title: In vitro phenotypic susceptibility of HIV-2 clinical isolates to CCR5 inhibitors.
abstract: HIV-2 is naturally resistant to nonnucleoside reverse transcriptase inhibitors, to a fusion inhibitor, and to some of the protease inhibitors. Maraviroc is the first drug of the new anti-CCR5 drug class and is effective only on CCR5-tropic (R5) HIV-1. No previous studies concerning HIV-2 susceptibility to maraviroc have been reported yet. We developed a phenotypic maraviroc susceptibility test using a peripheral blood mononuclear cell (PBMC) model. We analyzed the maraviroc susceptibility of 13 R5 HIV-2, 2 X4R5 (dual) HIV-2, and 2 CXCR4-tropic (X4) HIV-2 clinical isolates. We also tested, with the same protocol, 1 X4 HIV-1 and 4 R5 HIV-1 clinical isolates. For the R5 HIV-2 clinical isolates, the 50% effective concentration (EC(50)) for maraviroc was 0.80 nM (interquartile range [IQR], 0.48 to 1.39 nM), similar to that observed for the R5 HIV-1 isolates. The median maximum percentage of inhibition in the R5 HIV-2 isolates was 93% (IQR, 84 to 98%), similar to that observed in the R5 HIV-1 isolates. As expected, both X4 HIV-1 and HIV-2 were highly resistant to maraviroc. Our study showed for the first time that maraviroc is active in vitro against R5 HIV-2. The new tools we developed will allow identification of HIV-2-infected patients eligible for CCR5 inhibitor use and management of virological failure when receiving a maraviroc-based regimen.
authors: Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Université Paris Diderot, Sorbonne Paris Cité, EA4409, Paris, France.
authors: Benoit
authors: B
authors: Visseaux
authors: Charlotte
authors: C
authors: Charpentier
authors: Margarita
authors: M
authors: Hurtado-Nedelec
authors: Alexandre
authors: A
authors: Storto
authors: Romain
authors: R
authors: Antoine
authors: Gilles
authors: G
authors: Peytavin
authors: Florence
authors: F
authors: Damond
authors: Sophie
authors: S
authors: Matheron
authors: Françoise
authors: F
authors: Brun-Vézinet
authors: Diane
authors: D
authors: Descamps
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D002478:Cells, Cultured; D003510:Cyclohexanes / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D015498:HIV-2 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D000077592:Maraviroc; D008954:Models, Biological; D010835:Phytohemagglutinins / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013045:Species Specificity; D014230:Triazoles / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; C527276:CXCR4 protein, human; D003510:Cyclohexanes; D010835:Phytohemagglutinins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014230:Triazoles; D000077592:Maraviroc