Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration

The functional recovery of the immune system in HIV-infected persons receiv ing HAART and the role of adjuvant immune therapy are still matters of inte nsive investigation. We analysed the effects of HAART combined with cytokin es in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6 ), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plu s rIL-2 after previous administration of granulocyte colony-stimulating fac tor (n = 8). After 3 months of therapy, increased CD4(+) T cell counts and diminished viral loads were observed in all patients, independently of cyto kine addition. A decreased expression of CD95 (Apo 1/Fas) was evident in al l groups when compared with values before therapy. The percentages of perip heral blood mononuclear cells (PBMC) expressing CD95 after therapy decrease d by 15%, 22% and 18% in the three treatment groups, respectively (P < 0.05 ). Analysis of PBMC subsets demonstrated that CD95 expression was significa ntly reduced on CD45RA(+)CD62L(+) naive T cells (25.3%, 22.4%, and 18.6%, r espectively; P < 0.05) in each group, after therapy. Accordingly, all patie nts showed a reduced rate of in vitro spontaneous apoptosis (P < 0.05). Ano ther effect induced by HAART was a significant increase in IL-2R alpha expr ession on total PBMC (P < 0.05), independently of cytokine addition. Altoge ther, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the i mmune system as regards HAART alone. The employment of higher doses of reco mbinant cytokines and/or different administration protocols in clinical tri als might however contribute to ameliorate the immune reconstitution in pat ients undergoing HAART.