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 individuals (200-500 CD4/microl) were enrolled in a prospective study aimed at analyzing the immunologic and virologic effects of two different combinations 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 mitogen-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 (IFNgamma) production as well as the type 1/type 2 cytokine ratio and in down modulating the susceptibility of peripheral blood mononuclear cells to in vitro mitogen-stimulated apoptotic cell death. These data suggest that the combination of AZT+3TC has a stronger effect on potentially beneficial immune parameters (IL-2 production; reduction of apoptosis) than the one between AZT+ddI. The combination of AZT+3TC could be more advantageous in the therapy of HIV infection even when used in association with a protease inhibitor.
Piconi
S
S
Ia Divisione di Malattie Infettive, Ospedale L. Sacco, Milano, Italy.
Trabattoni
D
D
Fusi
M L
ML
Milazzo
F
F
Dix
L P
LP
Rizzardini
G
G
Colombo
F
F
Bray
D
D
Clerici
M
M
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D016207:Cytokines / Q000096:biosynthesis*; D016049:Didanosine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000502:physiology; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D018417:Th1 Cells / Q000276:immunology; D014766:Viremia; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D016207:Cytokines; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D016049:Didanosine