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.

1. To study the metabolism of α 1 -antitrypsin in man, radioiodinated purified α 1 -antitrypsin of protease inhibitor type MM was injected intravenously into seven normal volunteer subjects of protease inhibitor type MM and plasma and urine radioactivity data were analysed. The purified glycoprotein inhibited trypsin and exhibited micro-heterogeneity characteristic of α 1 -antitrypsin on acid starch-gel electrophoresis. 2. The intravascular mass was 116 ± 16.1 mg/kg (mean ± sem); extravascular/intravascular pool ratio was 1.07 ± 0.067; the fractional catabolic rate was 33.3 ± 1.37% of the intravascular pool/day; half-life was 4.6 ± 0.21 days; synthetic rate was 33.8 ± 6.3 mg day −1 kg −1 . 3. The data indicated that the serum concentration of α 1 -antitrypsin varies independently of its fractional catabolic rate and that it is catabolized in, or in close relationship to, the intravascular compartment. 4. Plasma curves of protein-bound radioactivity were also defined after the intravenous administration of 131 I-labelled desialylated α 1 -antitrypsin to two additional subjects. The fractional plasma disappearance rates were approximately 150 times as great as those for the intact protein. The rapid disappearance of 131 I-labelled desialylated α 1 -antitrypsin from plasma coincided with an equally rapid uptake of radioactivity by the liver. 5. The results are compatible with the existence of receptor sites for desialylated glycoproteins in the surface membrane of human hepatocytes and emphasize that the catabolism of α 1 -antitrypsin can be influenced by the structure of its carbohydrate moiety.