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.


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.
IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain.|Hospital Universitario Rey Juan Carlos, Móstoles, Spain.
Norma
N
Rallón
IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain.|Hospital Universitario Rey Juan Carlos, Móstoles, Spain.
Marcial
M
García
Hospital Universitario Carlos III-La Paz, Madrid, Spain.
Javier
J
García-Samaniego
IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain.|Hospital Universitario Rey Juan Carlos, Móstoles, Spain.
Noelia
N
Rodríguez
Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
Alfonso
A
Cabello
IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain.|Hospital Universitario Rey Juan Carlos, Móstoles, Spain.
Clara
C
Restrepo
Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
Beatriz
B
Álvarez
Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
Rosa
R
García
Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
Miguel
M
Górgolas
IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain.|Hospital Universitario Rey Juan Carlos, Móstoles, Spain.
José M
JM
Benito
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D060085:Coinfection / Q000209:etiology / Q000276:immunology*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000209:etiology / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018709:Statistics, Nonparametric; D019562:Viral Load / Q000276:immunology