Primary resistance to maraviroc in a large set of R5-V3 viral sequences from HIV-1-infected patients

• Published in: Journal of antimicrobial chemotherapy 2010-12, Vol.65 (12), p.2502-2504
• Main Authors: Seclén, Eduardo, González, María del Mar, Lapaz, Mariana, Rodríguez, Carmen, del Romero, Jorge, Aguilera, Antonio, de Mendoza, Carmen, Soriano, Vincent, Poveda, Eva
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Biological and medical sciences; Cyclohexanes - pharmacology; Cyclohexanes - therapeutic use; Drug resistance; Drug Resistance, Viral - genetics; HIV; HIV Envelope Protein gp120 - chemistry; HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp120 - metabolism; HIV Infections - drug therapy; HIV Infections - virology; HIV Seropositivity - drug therapy; HIV Seropositivity - virology; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; maraviroc; Medical sciences; Mutation; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptide Fragments - metabolism; Pharmacology. Drug treatments; Polymorphism; R5-tropic; Receptors, CCR5 - genetics; Receptors, CCR5 - metabolism; Sequence Analysis, DNA; Triazoles - pharmacology; Triazoles - therapeutic use; tropism; V3 loop; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Tropism
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkq381

Objectives Evaluation of the prevalence of V3 mutational patterns associated with maraviroc resistance in R5-using variants. Methods V3 sequences were obtained from 809 plasma specimens collected from maraviroc-naive HIV-1-infected individuals on regular follow-up at Hospital Carlos III. Sequences considered to harbour R5-tropic viruses were examined for the presence of primary maraviroc resistance mutational patterns, as found in both in vitro and in vivo studies. Results A total of 498 R5-V3 sequences were identified. They belonged to recent HIV-1 seroconverters (55.6%), chronically antiretroviral-naive subjects (20.1%) and antiretroviral-experienced patients (24.3%). Most individuals (93.8%) were infected with HIV-1 subtype B. The overall prevalence of maraviroc resistance mutational patterns was low (≤5%). Likewise, specific polymorphisms 4L, 11R or 19S, recently found to be associated with lower clinical response to maraviroc, were found in