Genetic Variability of Hepatitis C Virus (HCV) 5’ Untranslated Region in HIV/HCV Coinfected Patients Treated with Pegylated Interferon and Ribavirin

Abstract

Association between hepatitis C virus (HCV) quasispecies and treatment outcome among patients with chronic hepatitis C has been the subject of many studies. However, these studies focused mainly on viral variable regions (E1 and E2) and usually did not include human immunodeficiency virus (HIV)-positive patients. The aim of the present study was to analyze heterogeneity of the 5'untranslated region (5'UTR) in HCV/HIV coinfected patients treated with interferon and ribavirin. The HCV 5’UTR was amplified from serum and peripheral blood mononuclear cells (PBMC) samples in 37 HCV/HIV coinfected patients treated for chronic hepatitis C. Samples were collected right before treatment, and at 2, 4, 6, 8, 12, 20, 24, 36, 44, 48, 60, and 72 weeks. Heterogeneity of the 5'UTR was analyzed by single strand conformational polymorphism (SSCP), cloning and sequencing. Sustained virological response (SVR) was achieved in 46% of analyzed HCV/HIV co-infected patients. Stable SSCP band pattern was observed in 22 patients (62.9%) and SVR rate among these patients was 23%. Decline in the number of bands and/or shift in band positions were found in 6 patients (17.1%), 5 (83%) of whom achieved SVR (p=0.009). A novel viral genotype was identified in all but one of these patients. In 5 of these 6 patients a new genotype was dominant. 5'UTR heterogeneity may correlate with interferon and ribavirin treatment outcome. In the analyzed group of HCV/HIV coinfected patients, viral quasispecies stability during treatment favored viral persistence, whereas decrease in the number of variants and/or emergence of new variants was associated with SVR. Among injection drug users (IDU) patients, a new genotype may become dominant during treatment, probably due to the presence of mixed infections with various strains, which have different susceptibility to treatment.

Treatment Response and Drug Resistance Profiling of Genotype 6 of Hepatitis C Virus in HCV/HIV Co-Infected Patients: A Pilot Study from INDIA

“…In Asian countries, infection from HCV GT6 is most prevalent in Thailand, Myanmar, China, and Hong Kong [ 14 ]. HCV/HIV co-infection is often associated with increased genetic diversity in the HCV structural genes, probably due to immune pressure or viral persistence [ 4 , 15 ]. GT6 is the most prevalent genotype in the HCV/HIV co-infected cohort.…”

Inhibition of hepatitis C virus using siRNA targeted to the virus and Hsp90

“…Still on the efficiency difference observed in long-term treatment with siRNAs Hsp90 and 361 or 278, although the viral molecules are directed to the 5′UTR region of the virus, a highly conserved part of the genome, this site is also subject to mutation (Araujo et al 2008;Bukowska-Osko et al 2015), and therefore, an siRNA targeted to specific mutated region could have its efficiency decreased. Consequently, a mutation in the target region of the molecule 278 may have impaired this siRNA in the long-term test.…”

Phylogenetic Analysis and Genotyping Distribution of Hepatitis C Virus Isolates Based on the 5`Untranslated Region among some Egyptian Populations

“…The performance of diagnostic assays all may differentiated according to genotype (Costafreda et al, 2006). 5'UTR heterogeneity correlates with interferon and ribavirin treatment outcome as its stability correlated with non-response, whereas changes in this region were associated with Sustained virologic response (SVR) (Bukowska-Ośko et al, 2015) .…”