title: Effects of HCV co-infection on apoptosis of CD4+ T-cells in HIV-positive patients.
abstract: Apoptosis importantly contributes to loss of CD4+ T-cells in HIV infection, and modification of their apoptosis may explain why HIV/HCV (hepatitis C virus)-co-infected patients are more likely to die from liver-related causes, although the effects of HCV on HIV infection remain unclear. In the present study, 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 (highly active antiretroviral therapy). Apoptosis of peripheral blood CD4+ T-cells was measured by both a PARP [poly(ADP-ribose) polymerase] and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay to detect cells with irreversible apoptosis. Although 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 with 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 patient 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. The results of the present study 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.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Germany, Sigmund-Freud-Str. 25, Bonn 53127, Germany. christian.koerner@ukb.uni-bonn.de
authors.forename: Christian
authors.initials: C
authors.lastname: Körner
authors.forename: Benjamin
authors.initials: B
authors.lastname: Krämer
authors.forename: Daniela
authors.initials: D
authors.lastname: Schulte
authors.forename: Martin
authors.initials: M
authors.lastname: Coenen
authors.forename: Stefan
authors.initials: S
authors.lastname: Mauss
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D055815:Young Adult