EFFECT OF ZIDOVUDINE THERAPY ON CD8+ T-CELL ANTI-HIV ACTIVITY

CD8(+) T cell suppression of HIV replication in vitro was evaluated over 1-2 years in 12 HIV-infected individuals receiving daily dosages of Zidovudine (AZT) and in 9 untreated subjects. In the 12 AZT-treated patients, the level of CD8(+) cell antiviral activity increased an average of 6.6-fold above pretreatment levels. These increases in antiviral activity observed were only transient in 6 of the subjects, returning to pretreatment levels, or lower, over the study period. In the other 4 subjects, the CD8(+) cell antiviral response remained elevated at the end of the study period. The changes in CD8(+) cell responses did not correlate with observed alterations in the absolute number or the percentage of CD4(+) or CD8(+) peripheral blood lymphocytes. Untreated HIV-infected subjects generally showed a gradual decrease in the CD8(+) cell response over time to as much as 16-fold below baseline and in contrast to the treated group, these changes correlated with similar changes in CD4(+) cell counts (P = 0.02). The average level of CD8(+) cell antiviral activity observed over the entire study period was more than 2-fold above baseline in the 12 AZT-treated subjects, whereas it was more than 3-fold below baseline in the untreated subjects (P = 0.0001). Culturing CD8(+) cells in the continued presence of AZT (1 mu M) showed no effect on the ability of the cells to inhibit replication of an AZT-resistant HIV-1 strain. The results suggest that AZT therapy can have a beneficial effect. albeit often of limited duration, on CD8(+) T cell function in HIV-infected individuals. (C) 1994 Academic Press, Inc.