Abstract: Antiretroviral therapy (ART) significantly reduced the CD8+ cell noncytotoxic anti-HIV response in 12 HIV-1–infected subjects (P < 0.0001). In separate experiments, CD8+ cells from long-term survivors were cocultured with HIV-infected CD4+ cells using varying concentrations of anti-HIV drugs. The antiviral function of CD8+ cells from 4 of the 14 LTSs was reduced with exposure to 10 μM of nevirapine (P < 0.05). The antiviral activity of CD8+ cells from 2 LTSs was inhibited by 5 μM of zidovudine. These studies indicate that nevirapine and probably zidovudine can inhibit the anti-HIV activity of CD8+ cells and thus could influence the effectiveness of antiretroviral therapy.