Effects of HCV co-infection on apoptosis of CD4+ T cells in HIV-positive patients
Résumé
Background: Apoptosis importantly contributes to loss of CD4+ T cells in HIV infection, and modification of their apoptosis may explain why HIV/HCV-co-infected patients are more likely to die from liver-related causes, while effects of HCV on HIV infection remain unclear. Methods: We studied in a cross-sectional and serial analysis spontaneous ex vivo CD4+ T cell apoptosis in HIV/HCV-co-infected and HIV-mono-infected patients before and after HAART. Apoptosis of peripheral blood CD4+ T cells was measured by both, a Poly (ADP-ribose) polymerase (PARP) and TdT-mediated dUTP-FITC nick end labelling (TUNEL) assay to detect cells with irreversible apoptosis. Results: While hepatitis C alone did not increase CD4+ T cell apoptosis, HCV co-infection disproportionately increased elevated rates of apoptosis in CD4+ T cells from untreated HIV-positive patients. Increased CD4+ T cell apoptosis was closely correlated to HIV but not HCV viral loads. Under HAART increased rates of CD4+ T cell apoptosis rapidly decreased both in HIV-mono-infected and HIV/HCV-co-infected patients, without any significant difference in apoptosis rates between the two patients groups after 4 weeks of therapy. Nevertheless residual CD4+ T cell apoptosis did not reach the normal levels seen in healthy controls and remained higher in HIV patients receiving protease inhibitors than in patients with other antiretroviral regimens. Conclusions: Our results suggest that HCV co-infection sensitizes CD4+ T cells towards apoptosis in untreated HIV-positive patients. However, this effect is rapidly lost under effective antiretroviral therapy.
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