Hepatitis C virus quasispecies in HIV-infected women: role of injecting drug use and highly active antiretroviral therapy (HAART).

Hepatitis C virus (HCV) coinfection is common among HIV-infected patients. In the United States and Europe 13% to 43% of HIV-positive persons are coinfected with HCV1 and this proportion can be as high as 85% among intravenous drug users (IDU).2 HIV coinfection increases the risk of HCV-related cirrhosis3–6 and because of highly active antiretroviral therapy (HAART)-related reduction in mortality, HCV-associated liver disease has become the primary cause of death among HIV-positive patients.7 This deleterious effect of HIV coinfection could be conveniently explained by increased HCV replication secondary to immunodeficiency. However, there is some emerging evidence that HCV replication may be enhanced by HIV infection more directly, although the mechanism behind this interaction remains unclear. Thus, plasma HCV RNA levels have been found to be more closely associated with HIV RNA levels than with CD4+ T cell count,8 and HIV seroconversion in HCV-infected patients has been associated with a rapid increase in HCV replication.9 It has also been reported that HIV infection may facilitate HCV infection/replication in in vitro cell culture systems.10 Interestingly, there is some emerging evidence that HCV infection may negatively affect HIV disease as well as response to HAART.11,12 The detrimental effects of HIV on the course of HCV infection are further compounded by its effect on treatment outcome. In 2 large clinical trials, the overall rate of sustained virological response among HIV/HCV coinfected patients treated with pegylated interferon plus ribavirin ranged from 27% to 40%, but the response rate was only 14% to 29% among those infected with the most common genotype 1, which is a markedly lower success rate than in HIV-negative patients.13,14 HCV is genetically heterogeneous because of low viral RNA polymerase fidelity resulting from lack of proofreading 3′-5′ exonuclease activity within the enzyme.15,16 Because of high mutation rates, HCV circulates as a population of closely related but nonidentical genomes, referred to as quasispecies.16–18 The N terminus of the E2 protein gene, which is the most variable part of the entire HCV genome, is called hypervariable region 1 (HVR1).19,20 This region encodes for a prominent B cell epitope and its high mutation rate could be important for viral evasion of the host immune system.19,21–23 HCV quasispecies heterogeneity and dynamics has been extensively studied in various settings, including in those with acute and chronic hepatitis C, those receiving anti-HCV therapy, and following liver transplantation for HCV-related liver disease.24–28 However, despite the high frequency of HCV/HIV coinfection, HCV quasi-species have rarely been analyzed in HIV-positive patients. In the few studies that were published, the number of analyzed patients was small and the role of associated factors could not be properly analyzed.29–31 The current study is the first systematic analysis of quasispecies complexity and dynamics in a large cohort of HIV-positive women taking into account the impact of multiple epidemiological factors and HAART.