Open AccessHCV coinfection contributes to HIV pathogenesis by increasing immune exhaustion in CD8 T-cells
Author(s) -
Norma Rallón,
Marcial García,
Javier García-Samaniego,
Noelia Rodríguez,
Alfonso Cabello,
Clara Restrepo,
Beatriz Álvarez,
R. Garcı́a,
Miguel Górgolas,
José M. Benito
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0173943
Subject(s) - viremia , pathogenesis , cd38 , coinfection , immunology , cd8 , immune system , viral load , biology , population , medicine , virology , virus , genetics , stem cell , environmental health , cd34
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.