HCV coinfection contributes to HIV pathogenesis by increasing immune exhaustion in CD8 T-cells

BACKGROUND: There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. PATIENTS AND METHODS: Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study. All patients were untreated for both infections. Several CD4 and CD8 T-cell subsets involved in HIV-pathogenesis were investigated. Non-parametric tests were used to establish differences between groups and associations between variables. Multivariate linear regression was used to ascertain the variables independently associated with CD4 counts. RESULTS: HIV-patients presented significant differences compared to healthy controls in most of the parameters analyzed. Both HIV and HIV/HCV groups were comparable in terms of age, CD4 counts and HIV-viremia. Compared to HIV group, HIV/HCV group presented significantly higher levels of exhaustion (Tim3(+)PD1(-) subset) in total CD8(+) T-cells (p = 0.003), and higher levels of exhaustion in CD8(+)HLADR(+)CD38(+) (p = 0.04), CD8(+)HLADR(-)CD38(+) (p = 0.009) and CD8(+)HLADR(-)CD38(-) (p = 0.006) subsets of CD8(+) T-cells. Interestingly these differences were maintained after adjusting by CD4 counts and HIV-viremia. CONCLUSIONS: We show a significant impact of HCV-coinfection on CD8 T-cells exhaustion, an important parameter associated with CD8 T-cell dysfunction in the setting of chronic HIV-infection. The relevance of this phenomenon on immunological and/or clinical HIV progression prompts HCV treatment to improve management of coinfected patients.