HCV genotypes, characterization of mutations conferring drug resistance to protease inhibitors, and risk factors among blood donors in São Paulo, Brazil.
BACKGROUND
Hepatitis C virus (HCV) infection is a global health problem estimated to affect almost 200 million people worldwide. The aim of this study is to analyze the subtypes and existence of variants resistant to protease inhibitors and their association with potential HCV risk factors among blood donors in Brazil.


METHODS
Repeat anti-HCV reactive blood donors are systematically asked to return for retest, notification, and counseling in which they are interviewed for risk factors for transfusion-transmitted diseases. We analyzed 202 donors who returned for counseling from 2007 to 2010 and presented enzyme immunoassay- and immunoblot-reactive results. The HCV genotypes and resistance mutation analyses were determined by the direct sequencing of the NS5b and NS3 regions, respectively. The HCV viral load was determined using an in-house real-time PCR assay targeting the 5'-NCR.


RESULTS
HCV subtypes 1b, 1a, and 3a were found in 45.5%, 32.0%, and 18.0% of the donors, respectively. The mean viral load of genotype 1 was significantly higher than that of the genotype 3 isolates. Subtype 1a was more frequent among young donors and 3a was more frequent among older donors. Protease inhibitor-resistant variants were detected in 12.8% of the sequenced samples belonging to genotype 1, and a higher frequency was observed among subtype 1a (20%) in comparison to 1b (8%). There was no difference in the prevalence of HCV risk factors among the genotypes or drug-resistant variants.


CONCLUSIONS
We found a predominance of subtype 1b, with an increase in the frequency of subtype 1a, in young subjects. Mutations conferring resistance to NS3 inhibitors were frequent in treatment-naïve blood donors, particularly those infected with subtype 1a. These variants were detected in the major viral population of HCV quasispecies, have replicative capacities comparable to nonresistant strains, and could be important for predicting the response to antiviral triple therapy.
Fundação Pró-Sangue/Hemocentro de São Paulo, São Paulo, Brazil ; Infectious Diseases Division (DIPA), Federal University of São Paulo, São Paulo, Brazil.
Anna S
AS
Nishiya
Fundação Pró-Sangue/Hemocentro de São Paulo, São Paulo, Brazil ; Discipline of Medical Science, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Cesar
C
de Almeida-Neto
Fundação Pró-Sangue/Hemocentro de São Paulo, São Paulo, Brazil ; Infectious Diseases Division (DIPA), Federal University of São Paulo, São Paulo, Brazil.
Suzete C
SC
Ferreira
Infectious Diseases Division (DIPA), Federal University of São Paulo, São Paulo, Brazil ; LIM 03 Lab. Medice Laboratory, Department of Pathology, HCFMUSP, São Paulo, Brazil.
Cecília S
CS
Alencar
University of São João del-Rei, Divinópolis, Minas Gerais, Brazil.
Claudia
C
Di-Lorenzo-Oliveira
Fundação Pró-Sangue/Hemocentro de São Paulo, São Paulo, Brazil.
José E
JE
Levi
Fundação Pró-Sangue/Hemocentro de São Paulo, São Paulo, Brazil.
Nanci A
NA
Salles
Fundação Pró-Sangue/Hemocentro de São Paulo, São Paulo, Brazil.
Alfredo
A
Mendrone
Infectious Diseases Division (DIPA), Federal University of São Paulo, São Paulo, Brazil ; Department of Infectious Disease, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Ester C
EC
Sabino
D000293:Adolescent; D000328:Adult; D001782:Blood Donors; D001938:Brazil / Q000453:epidemiology; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D055815:Young Adult
D011480:Protease Inhibitors