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Journal Articles Journal of Antimicrobial Chemotherapy Year : 2015

Virological failure of patients on maraviroc-based antiretroviral therapy

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

Dates and versions

hal-01274888 , version 1 (16-02-2016)

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Stéphanie Raymond, Anne Maillard, Corinne Amiel, Gilles Peytavin, Mary Anne Trabaud, et al.. Virological failure of patients on maraviroc-based antiretroviral therapy. Journal of Antimicrobial Chemotherapy, 2015, 70 (6), pp.1858--1864. ⟨10.1093/jac/dkv026⟩. ⟨hal-01274888⟩
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