title: Dynamic of Mixed HCV Infection in Plasma and PBMC of HIV/HCV Patients Under Treatment With Peg-IFN/Ribavirin.
abstract: The extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown.The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate.The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P-R). Ten individuals were nonresponder (NR) or relapser (RE) to P-R treatment and 9 had a sustained virological response (SVR).Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV-RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P-R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237).Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P-R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG.
authors.affiliation: Infectious Diseases Department, Scientific Institute Ospedale San Raffaele, Via Stamira d'Ancona 20, 20127 Milan, Italy (SB, CU-F, AA, HH, EM, MM, AL, GM); Vita-Salute University Via Olgettina 58, 20132 Milan, Italy (SB, AL); University Centre for Statistics in the Biomedical Sciences (CUSSB) Vita-Salute San Raffaele University, Via Olgettina 58, 20132 Milan, Italy (CDS, FT); L. Bocconi University, Via R. Sarfatti 25, 20136 Milan, Italy (FT); Mol Med Spa, Via Olgettina 58, 20132 Milan, Italy (LP).
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bagaglio
authors.forename: Caterina
authors.initials: C
authors.lastname: Uberti-Foppa
authors.forename: Clelia
authors.initials: C
authors.lastname: Di Serio
authors.forename: Filippo
authors.initials: F
authors.lastname: Trentini
authors.forename: Andrea
authors.initials: A
authors.lastname: Andolina
authors.forename: Hamid
authors.initials: H
authors.lastname: Hasson
authors.forename: Emanuela
authors.initials: E
authors.lastname: Messina
authors.forename: Marco
authors.initials: M
authors.lastname: Merli
authors.forename: Lucy
authors.initials: L
authors.lastname: Porrino
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Giulia
authors.initials: G
authors.lastname: Morsica
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D001825:Body Fluid Compartments / Q000821:virology; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000821:virology; D015658:HIV Infections / Q000150:complications; D016898:Interferon-alpha / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000821:virology; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C100416:peginterferon alfa-2a; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin