title: Evolution of HVR-1 quasispecies after 1-year treatment in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy.
abstract: Hepatitis C virus (HCV) variability is mainly attributed to the ability of the virus to respond to host immune pressure, acting as a driving force for the evolution of quasispecies. This study was aimed at studying the changes in HVR-1 heterogeneity and the evolution of HCV quasispecies in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy (HAART). Sixteen HIV/HCV-coinfected patients harbouring HCV genotype 1 and who had been on HAART for at least 1 year, 8 showing increasing CD4+ T-cell counts (immunological responders) and 8 showing a stable or decreasing CD4+ T-cell counts (immunological nonresponders), were selected from a prospective cohort study. After 1 year of HAART, 11 patients showed HIV viral load <2.6 log10 cp/ml (virological responders), and 5 showed HIV viral load above this value (virological non-responders). Plasma samples, collected before starting therapy and after 1 year of HAART, underwent clonal sequence analysis for HVR-1 region of HCV. Nonsynonymous/synonymous substitutions ratio (Ka/Ks), aminoacidic complexity (normalized Shannon entropy) and diversity (p-distance), were considered as parameters of quasispecies heterogeneity. After 1 year of HAART, heterogeneity of HVR-1 quasispecies significantly decreased in virological non-responders, whereas the heterogeneity tended to increase in virological responders. The differences in the evolution were less stringent, when considering immunological response. On the other hand, profound qualitative modifications of HVR-1 quasispecies were observed only in patients with both immunological and virological HAART response. On the whole, these findings suggest that, in patients undergoing HAART, the extent of HCV variability and the evolution of HVR-1 quasispecies is influenced by the pattern of response to antiretroviral therapy.
authors.affiliation: National Institute of Infectious Diseases L Spallanzani, Rome.
authors.forename: Mariacarmela
authors.initials: M
authors.lastname: Solmone
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lalle
authors.forename: Isabella
authors.initials: I
authors.lastname: Abbate
authors.forename: Antonella
authors.initials: A
authors.lastname: D'Arminio Monforte
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Anna
authors.initials: A
authors.lastname: Alessandrini
authors.forename: Rita
authors.initials: R
authors.lastname: Piscopo
authors.forename: Francesca
authors.initials: F
authors.lastname: Ebo
authors.forename: Lucio
authors.initials: L
authors.lastname: Cosco
authors.forename: Giorgio
authors.initials: G
authors.lastname: Antonucci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.forename: Maria R
authors.initials: MR
authors.lastname: Capobianchi
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D019143:Evolution, Molecular; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load; D014764:Viral Proteins / Q000145:classification / Q000235:genetics*
chemical_list: C400562:HVR1 protein, Hepatitis C virus; D012367:RNA, Viral; D014764:Viral Proteins