Hepatitis C virus (HCV) genomic characterization at 5’ UTR in HIV-HCVcoinfected subjects under highly active antiretroviral therapy: 4-8 yrs follow-up.

FRANCO MORETTI; FEDERICO BOLCIC; NATALIA LAUFER; JORGE QUARLERI

Lisboa, Portugal

Workshop; 5th International Workshop on HIV and Hepatitis Co-infection; 2009

BACKGROUND Due to the increased mortality and reduced treatment response rates in subjects coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), understanding the selection pressures underlying the evolution of HCV is important for the development of strategies to control both viruses. The HCV genome contains a highly conserved region, the 5´ untranslated region (5´ UTR), where mutations are rare, preserving the base-pairing pattern in order to conserve structural properties related to translation efficiency. We therefore investigated diversity of HCV in HIV coinfection for 4-8 years of highly active antiretroviral therapy (HAART). PATIENTS & METHODS Eleven patients chronically coinfected with HCV and HIV were retrospectively studied for 4 to 8 years previous to anti-HCV therapy based on peg-IFN plus ribavirin (3 for 4 years; 1 for 5 years; 1 for 7 years and 6 for 8 years). For each patient, one serum sample/year was analyzed. All the patients were under HAART from the beginning of the follow-up. HCV RNA was isolated from serum samples and amplified using RT-nested PCR, producing a 250 bp amplicon, which was further sequenced to establish phylogenetic relatedness based on distance methods. RESULTS HCV RNA was found in 66 out of 72 samples from 11 patients. The HCV genotypic distribution was 6/11 (54.54%) genotype (Gt) 1; 1/11 (9.09%) Gt2; 2/11 (18.18%) Gt3 and 2/11 (18.18%) both Gt1 and Gt2. A high degree of genomic conservation was observed among 5’ UTR sequences from each patient during the follow-up regardless of the HAART regimen, CD4 T cell count, and HCV genotype. CONCLUSIONS The present data showed that no shift in the hepatitis C virus population occurs based on 5´ UTR genomic sequence under HAART pressure. Variations in the 5´ UTR were limited and steadily preserved during the follow-up for each patient. As extensively reported, the HCV 5’ UTR is highly conserved in monoinfected patients without previous interferon-based therapy. In this study, this was also found even during prolonged HAART in HIV-coinfection.