title: Hepatitis C virus long-term persistence in peripheral blood mononuclear cells in patients with haemophilia. Detection of occult genotype 1.
abstract: Peripheral blood mononuclear cells (PBMC) from chronic hepatitis C virus-infected persons can harbour viral variants that are not detected in plasma samples. We explored the presence and persistence of HCV genotypes in plasma and PBMC cultures from 25 HCV-monoinfected and 25 HIV/HCV-coinfected patients with haemophilia. Cell cultures were performed at different time points between 1993 and 2010-2011, and the HCV genome was examined in culture supernatants. Sequential plasma samples were studied during the same time period. Analysing sequential plasma samples, 21% of patients had mixed-genotype infections, while 50% had mixed infections determined from PBMC culture supernatants. HIV coinfection was significantly associated with the presence of mixed infections (OR = 4.57, P = 0.02; 95% CI = 1.38-15.1). In our previous study, genotype 1 was found in 72% of 288 patients of this cohort. Similar results were obtained with the sequential plasma samples included in this study, 69% had genotype 1. However, when taking into account plasma samples and the results from PBMC supernatants, genotype 1 was identified in 94% of the population. The PBMC-associated variants persisted for 10 years in some subjects, emphasizing their role as long-term reservoirs. The presence of genotype 1 in PBMC may be associated with therapeutic failure and should not be disregarded when treating haemophilic patients who have been infected by contaminated factor concentrates. The clinical implications of persistent lymphotropic HCV variants deserve further examination among multiple exposed groups of HCV-infected patients.
authors.affiliation: Virology Laboratory, Instituto de Investigaciones Hematológicas, Instituto de Medicina Experimental, CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Parodi
authors.affiliation: Cátedra de Virología. Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: García
authors.affiliation: Virology Laboratory, Instituto de Investigaciones Hematológicas, Instituto de Medicina Experimental, CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: M C
authors.initials: MC
authors.lastname: Monzani
authors.affiliation: Cátedra de Virología. Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Culasso
authors.affiliation: Virology Laboratory, Instituto de Investigaciones Hematológicas, Instituto de Medicina Experimental, CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: N
authors.initials: N
authors.lastname: Aloisi
authors.affiliation: Fundación Argentina de la Hemofilia, Buenos Aires, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Corti
authors.affiliation: Cátedra de Virología. Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: R
authors.initials: R
authors.lastname: Campos
authors.affiliation: Virology Laboratory, Instituto de Investigaciones Hematológicas, Instituto de Medicina Experimental, CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: M M
authors.initials: MM
authors.lastname: de E de Bracco
authors.affiliation: Virology Laboratory, Instituto de Investigaciones Hematológicas, Instituto de Medicina Experimental, CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: P
authors.initials: P
authors.lastname: Baré
mesh_terms: D000328:Adult; D000368:Aged; D060085:Coinfection / Q000821:virology; D005838:Genotype; D015658:HIV Infections / Q000150:complications; D006467:Hemophilia A / Q000150:complications*; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000150:complications* / Q000821:virology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D008875:Middle Aged
keywords: HCV mixed genotypes; HIV/HCV coinfection; Hepatitis C virus; peripheral blood mononuclear cells; persistence