Evaluating the impact of hepatitis C virus (HCV) on highly active antiretroviral therapy-mediated immune responses in HCV/HIV-coinfected women : Role of HCV on expression of primed/ memory T cells

Between 30% and 100% of HIV-infected patients are coinfected with hepatitis C virus (HCV) [1–4]. A number of studies have negatively associated HIV with the progression of HCV disease [5–7]. HIV accelerates HCV-associated complications, such as liver cirrhosis, end-stage liver disease, and hepatocellular carcinoma. The impact of HCV on the progression of HIV disease is less clear—there have been a number of discordant findings. Some studies have reported that HCV accelerates the progression of HIV disease [8–11], whereas others found no impact [12, 13]. Variation in the definition of the progression of HIV disease—based on incidences of opportunistic infections or decreases in CD4+ T cell count, sample size, duration of follow-up, and other cofounding variables—may have contributed to these conflicting findings. Few studies have evaluated the effect of HCV co-infection on immune recovery after the initiation of highly active antiretroviral therapy (HAART). In those studies, immune recovery was defined by either the magnitude or rate of increases in CD4+ T cell counts over time, with controversial findings. Some studies have reported that the level and rate of increases in CD4+ T cell counts are lessened and slower in coinfected than in monoinfected patients [10, 14, 15], whereas others did not find a negative association between HCV coinfection and CD4+ T cell responses after the initiation of HAART [16–18]. None of these studies, however, evaluated a larger breadth of immunophenotypic markers relevant to immune function. Through the Women’s Interagency HIV Study (WIHS), a multicenter cohort established in 1993 in the United States, where ~39% of HIV-infected women are coinfected with HCV, we retrospectively evaluated the impact of HIV/HCV coinfection on immune recovery after the initiation of HAART between HIV-monoinfected women and women coinfected with HCV who have either cleared or did not clear HCV. Immune recovery was evaluated by examining alterations in CD4+ and CD8+ T cell counts and alterations in the dynamics of activation and naive/memory T cell status within the CD4+ and CD8+ T cell compartments.