Previous failure to interferon-based therapy does not alter the frequency of HCV NS3-protease or NS5B-polymerase inhibitors resistance variants: longitudinal analysis in HCV/HIV coinfected patients

SEDE M, LAUFER NL, QUARLERI J

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015

0924-8579

Background. Since 2011 treatment of chronic HCV includes direct antiviral agents (DAA) in addition to pegylated interferon-α and ribavirin (peg-IFN+RBV). IFN-based treatment induces a strong cytotoxic T lymphocyte activity directed to the protease and polymerase-derived epitopes. This enhanced immunological pressure could favor the emergence of viral epitope variants able to evade immune surveillance and when RAVs are implied, could also be co-selected as a hitchhiking effect. Objective. To analyze the dynamics of the frequency of protease and polymerase inhibitors RAVs that could affect future HCV treatment in HIV-coinfected patients on stable antiretroviral therapy with previous IFN-based treatment failure. Methods. HCV genotype 1a RNA was extracted from plasma samples of 18 patients previous and during (24h, and 4, 12, 24, and 48 weeks) peg-IFN+RBV therapy. Next-generation sequencing (454 FLX, Roche) was performed on HCV RNA populations using NS3 and NS5B PCR-amplified coding region. Two measures of genetic diversity were used to compare virus populations: average pairwise nucleotide diversity (π) and Tajima?s D statistic. Results. Several protease and polymerase RAVs were detected in all subjects at very low frequencies (