Spontaneous and anti-Fas-induced apoptosis in lymphocytes from HIV-infected patients undergoing highly active anti-retroviral therapy

Objective: The aim of this study was to investigate susceptibility to spont aneous or anti-fas-induced apoptosis in peripheral blood mononuclear cells (PBMC) from HIV-positive patients before and during highly active anti-retr oviral therapy (HAART). Design: A longitudinal study was performed on 12 evaluable patients on HAAR T. This cohort was analysed prior to and at week 2, 4, 8, 16 and 24 after b eginning HAART. Variations in CD4 and CD8 cells, viral load, susceptibility to spontaneous or anti-fas-induced apoptosis in the presence of IL-2, IL-4 or IL-12 were studied. Expression of Fas and Bcl-2 were also assessed. Methods: Levels of HIV RNA were determined by a quantitative reverse transc ription-PCR assay. Apoptosis was evaluated by staining isolated nuclei with propidium iodide followed by multiparameter flow cytometry analysis. Results: Spontaneous apoptosis of PBMC was promptly inhibited after the sta rt of treatment. Similarly, anti-fas-induced apoptosis diminished greatly d uring treatment. Expression of Fas decreased significantly, while that of B cl-2 remained statistically unchanged during the first 24 weeks of therapy. Levels of apoptosis correlated inversely to CD4 cell counts and directly t o viral load in a highly significant way. Expression of Fas was directly co rrelated to apoptosis. Interleukin (IL)-2, but not IL-4 or IL-12, protected PBMC of HIV-positive individuals from spontaneous or anti-Fas-induced apop tosis before and during HAART. Conclusion: These results suggest that regulation of apoptosis and of Fas e xpression are involved in immunoreconstitution during HAART. (C) 2000 Lippi ncott Williams & Wilkins.