Effect of two different combinations of antiretrovirals (AZT+ddI and AZT+3TC) on cytokine production and apoptosis in asymptomatic HIV infection

Nineteen HIV-seropositive antiretroviral therapy-naive and asymptomatic ind ividuals (200-500 CD4/mu l) were enrolled in a prospective study aimed at a nalyzing the immunologic and virologic effects of two different combination s of nucleoside reverse transcriptase inhibitors (AZT + ddI and AZT + 3TC), and randomly assigned to one of the treatment group. Immunologic (CD4 and CD8 counts, mitogen-stimulated cytokine production, unstimulated and mitoge n-stimulated apoptosis) and virologic (HIV viral load) determinations were performed pre-therapy and 15, 30, 90, 200 and 360 days after initiation of therapy. Results showed that the two combinations had comparable effects on increasing CD4 counts and the CD4/CD8 ratio and in reducing HIV viral load . In contrast, AZT + 3TC was more efficient in improving interleukin-2 (IL- 2) and interferon gamma (IFN gamma) production as well as the type 1/type 2 cytokine ratio and in down modulating the susceptibility of peripheral blo od mononuclear cells to in vitro mitogen-stimulated apoptotic cell death. T hese data suggest that the combination of AZT + 3TC has a stronger effect o n potentially beneficial immune parameters (IL-2 production; reduction of a poptosis) than the one between AZT + ddl. The combination of AZT + 3TC coul d he more advantageous in the therapy of HIV infection even when used in as sociation with a protease inhibitor. (C) 2000 Elsevier Science B.V. All rig hts reserved.