Virological failure of patients on maraviroc-based antiretroviral therapy. (19th February 2015)

• Record Type: Journal Article
• Authors: Raymond, Stéphanie; Maillard, Anne; Amiel, Corinne; Peytavin, Gilles; Trabaud, Mary Anne; Desbois, Delphine; Bellecave, Pantxika; Delaugerre, Constance; Soulie, Cathia; Marcelin, Anne Geneviève; Descamps, Diane; Izopet, Jacques; Reigadas, S.; Bellecave, P.; Pinson-Recordon, P.; Fleury, H.; Masquelier, B.; Signori-Schmuck, A.; Morand, P.; Bocket, L.; Mouna, L.; André, P.; Tardy, J. C.; Trabaud, M. A.; Descamps, D.; Charpentier, C.; Peytavin, G.; Brun-Vézinet, F.; Haim-Boukobza, S.; Roques, A. M.; Soulié, C.; Lambert-Niclot, S.; Malet, I.; Wirden, M.; Fourati, S.; Marcelin, A. G.; Calvez, V.; Flandre, P.; Assoumou, L.; Costagliola, D.; Morand-Joubert, L.; Delaugerre, C.; Schneider, V.; Amiel, C.; Giraudeau, G.; Maillard, A.; Nicot, F.; Izopet, J.;
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 70:Number 6(2015:Jun.)
• Page Start: 1858
• Page End: 1864
• Publication Date: 2015-02-19
• Subjects: HIV-1 tropism determination -- entry -- phenotypic assay -- resistance to maraviroc -- CXCR4; Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkv026
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Objectives: Virological failure (VF) in patients on maraviroc-based treatment has been associated with altered HIV tropism and resistance to maraviroc. This multicentre study aimed to characterize VF in patients treated with maraviroc. Methods: We analysed 27 patients whose treatment failed between 2008 and 2011. They had been screened for HIV tropism before maraviroc initiation using population-based V3 genotyping. HIV-1 tropism and resistance of R5 viruses to maraviroc at VF and at baseline were determined retrospectively using an ultrasensitive recombinant virus assay (RVA). Results: Viruses from 27 patients given maraviroc on the basis of the R5 genotype were characterized at the time of treatment failure. The RVA indicated that 12 patients harboured CXCR4-using viruses and 15 (56%) had pure R5 viruses at failure. One-third of those harbouring CXCR4-using viruses (4/12) were infected with R5X4/X4 viruses according to the RVA before maraviroc initiation. We analysed the phenotypic resistance to maraviroc of four patients harbouring R5 viruses at failure; two harboured viruses whose maximum percentage inhibition was reduced by 65%–90%, while the other two were infected with susceptible viruses. All patients had effective concentrations of drugs. Conclusions: Half of the maraviroc-treated patients who experienced VF harboured CXCR4-using viruses at failure, one-third of them were detected by a phenotypic method before maraviroc initiation. Phenotypic assessment of R5 virus resistance to CCR5 antagonists at failure could help optimize antiretroviral therapy.