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

<div><p>Background</p><p>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.</p><p>Patients and methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p>