Virological failure of patients on maraviroc-based antiretroviral therapy

Stéphanie Raymond (1, 2, 3) , Anne Maillard (4, 5) , Corinne Amiel (6) , Gilles Peytavin (7, 8) , Mary Anne Trabaud , Delphine Desbois , Pantxika Bellecave (9, 10) , Constance Delaugerre (11) , Cathia Soulie (12, 13) , Anne Geneviève Marcelin (13) , Diane Descamps (7) , Jacques Izopet (3)

1 CPTP - Centre de Physiopathologie Toulouse Purpan
2 UT3 - Université Toulouse III - Paul Sabatier
3 Laboratoire Virologie [CHU Toulouse]
4 CHU Pontchaillou [Rennes]
5 CIC - Centre d'Investigation Clinique [Rennes]
6 CHU Tenon [AP-HP]
7 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
8 Service de pharmacocinétique clinique
9 MFP - Microbiologie Fondamentale et Pathogénicité
10 Service de virologie et d'immunologie biologique
11 Service de microbiologie [Saint-Louis]
12 Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH
13 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique

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

Keywords: Adult; Aged; Anti-Retroviral Agents; Antiretroviral Therapy; Highly Active; CXCR4; Cyclohexanes; Drug Resistance; Viral; entry; Female; HIV-1; HIV-1 tropism determination; HIV Infections; Humans; Male; Middle Aged; phenotypic assay; resistance to maraviroc; Retrospective Studies; Treatment Failure; Triazoles; Viral Load; Viral Tropism

Domains: Life Sciences [q-bio]

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⟩