Genetic Variability of Hepatitis C Virus (HCV) 5' Untranslated Region in HIV/HCV Coinfected Patients Treated with Pegylated Interferon and Ribavirin.
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.
Department of Immunopathology, Warsaw Medical University, Warsaw, Poland.
Iwona
I
Bukowska-Ośko
Department of Immunopathology, Warsaw Medical University, Warsaw, Poland.
Agnieszka
A
Pawełczyk
Department of Immunopathology, Warsaw Medical University, Warsaw, Poland.
Karol
K
Perlejewski
Department of Immunopathology, Warsaw Medical University, Warsaw, Poland.
Natalia
N
Kubisa
Department of Immunopathology, Warsaw Medical University, Warsaw, Poland.
Kamila
K
Caraballo Cortés
Department of Epidemiology, National Institute of Hygiene, Warsaw, Poland.
Magdalena
M
Rosińska
Department of the Medical Genetics, Warsaw Medical University, Warsaw, Poland.
Rafał
R
Płoski
Department of Immunopathology, Warsaw Medical University, Warsaw, Poland.
Maria
M
Fic
Department of Immunopathology, Warsaw Medical University, Warsaw, Poland.
Justyna
J
Kaźmierczak
Department of Immunopathology, Warsaw Medical University, Warsaw, Poland.
Marta
M
Popiel
Hospital of Infectious Diseases, Warsaw, Poland.
Piotr
P
Ząbek
Hospital of Infectious Diseases, Warsaw, Poland.
Andrzej
A
Horban
Department of Immunopathology, Warsaw Medical University, Warsaw, Poland.
Marek
M
Radkowski
Department of Immunopathology, Warsaw Medical University, Warsaw, Poland.
Tomasz
T
Laskus
D020121:5' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D001483:Base Sequence; D060085:Coinfection / Q000188:drug therapy* / Q000821:virology*; D005260:Female; D014644:Genetic Variation; D006678:HIV / Q000187:drug effects / Q000235:genetics*; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D016415:Sequence Alignment; D016896:Treatment Outcome; D055815:Young Adult
D020121:5' Untranslated Regions; D000998:Antiviral Agents; D016898:Interferon-alpha; D007378:Interleukins; D012254:Ribavirin