HCV drug resistance mutations in HIV-infected patients

Abstract

The aim of our work was to assess prevalence in the HCV drug resistance mutations in the NS3, NS5A, NS5B genes in HIV-infected patients. The material of the study was 157 blood plasma samples collected from HIV patients living in the Leningrad Region, with virological inefficiency of antiretroviral therapy. Samples were examined for the presence of anti-HCV antibodies and HCV RNA using commercial test systems in accordance with the manufacturer’s recommendations. In the case of detecting HCV RNA, amplification reaction was carried out using a set of primers co-flanking the NS3, NS5A, and NS5B genes. After sequencing the nucleotide sequences of the above genes, the virus subtype was determined. To assess HCV drug resistance mutations to direct-acting antiviral agents (DAAs), the Geno2pheno HCV resistance software (https:// hcv.geno2pheno.org) was used. The age of the patients varied from 18 to 65 and averaged 34.3±7.27 years. The number of males vs females prevailed comprising 71% and 28%, respectively. Antibodies against HCV were detected in 94.2% cases, whereas HCV RNA — in 98 (61.7%) HIV-infected persons. The distribution of HCV genotypes in this group was as follows: 1a — 7% (n = 7), 1b — 53% (n = 52), 2 — 2% (n = 2), 3a — 38% (n = 37). The results of determining the viral load varied from 5.3 × 103 to 2.3 × 108 IU/ml. The nucleotide sequence of all three regions NS3, NS5A, NS5B was determined in 73 samples. Analysis of drug resistance mutations in the NS3 region was performed for 82 HCV isolates of genotypes 1b (n = 46), 3a (n = 31), 1a (n = 4), 2 (n = 1). In total, the proportion of strains containing mutations in the NS3 region was 9.8%. The presence of significant amino acid substitutions in the NS5A region was tested for 83 HCV isolates of genotypes 1b (n = 47), 3a (n = 30), 1a (n = 6). The percentage of strains containing mutations in the NS5A region was 19.3%. Resistance mutations in the NS5B region were analysed for 87 HCV isolates of genotypes 1b (n = 48), 3a (n = 32), 2 (n = 2), 1a (n = 5). The proportion of strains containing mutations in the NS5B region was 11.5%. In the study group, mutations associated with hepatitis C virus resistance to DAAs in all regions were found in 16.6% (95% CI: 11.11–23.32%) cases (n = 26). In the NS3, NS5A and NS5B, there have been identified 6, 15 and 10 significant amino acid substitutions, respectively.