Longitudinal analysis of the 5′UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients

• Published in: Antiviral research 2012-08, Vol.95 (2), p.72-81
• Main Authors: Bolcic, Federico, Laufer, Natalia, Torres, Carolina, Cassino, Lucila, Reynoso, Rita, Quarleri, Jorge
• Format: Article
• Language: English
• Subjects: Genotype 1a; HCV; HIV; Pegylated interferon; Ribavirin
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2012.05.015

► Longitudinal analysis of IFN non-responsiveness on HIV-HCV and HCV infection. ► The number amino acid mutation at NS5A-ISDR was higher when HIV coexists. ► IFN-based therapy did not affect diversity of HCV-1a 5′UTR, E2-PePHD, NS5A-PKRBD. The rate of non-response to pegylated interferon plus ribavirin (peg-IFN+RBV) in HCV/HIV coinfected patients is higher than in HCV-monoinfected patients. In this sense, the contribution of HCV genetic variability is unknown. The 5′ untranslated (5′UTR), the nonstructural 5A (NS5A) and the second envelope (E2) HCV genomic regions have been implicated to peg-IFN therapy response. The proteins appear to block interferon (IFN)-induced RNA-dependent protein kinase (PKR) and the 5′UTR may influence the viral lymphotropism. We examined comparatively the pretreatment HCV variability between HIV coinfected and HCV monoinfected patients as well as assessed longitudinally the impact of peg-IFN+RBV on HCV variability when HIV is co-present. For this purpose, 15 HIV coinfected and 20 HCV monoinfected patients were compared. They were peg-IFN+RBV non-responders and infected with HCV 1a. Irrespectively of the HIV-coexistence, at baseline the amino acid variation in the NS5A-related domains was significantly higher than in the E2-PePHD (p