HIV Infection and Antiretroviral Therapy: Effect on Hepatitis C Virus Quasispecies Variability

Abstract

Hepatitis C virus (HCV) quasispecies variability has been associated with liver disease progression. The effects of human immunodeficiency virus (HIV) coinfection and highly active antiretroviral therapy (HAART) on HCV quasispecies variability have not been firmly established. We determined HCV quasispecies complexity and diversity in 69 subjects, 28 of whom were HIV infected, using clonal frequency analysis via heteroduplex mobility analysis of the second envelope gene hypervariable region. Nucleotide sequencing was performed for a small subset of subjects. HIV-positive, HAART-naive subjects had significantly lower HCV quasispecies complexity and diversity than did both HIV-negative and HIV-positive HAART-treated subjects. In multivariate analysis, HIV infection predicted decreased complexity (P < .0001) and diversity (P = .001) of HCV quasispecies, whereas HAART predicted increased complexity (P = .013) and diversity (P = .026). For 4 of 6 patients, sequence analysis yielded data supporting the model that positive host pressure drives HCV quasispecies heterogeneity, although data favoring the hypothesis of selective outgrowth of the most fit variants were also observed. HIV coinfection is associated with decreased HCV quasispecies variability, which appears to be reversed by effective HAART. Although HIV- and HAART-related effects on host immune pressure are likely to play a role in the observed differences in HCV genetic heterogeneity, other mechanisms may be operative.