Decreased HIV-associated T cell apoptosis by HIV protease inhibitors

Antiretroviral treatment of patients infected with HIV results in improvements in CD4⁺ T cell number. Emerging evidence suggests that some of the improvements-in CD4⁺ T cell number that occur in response to protease inhibitor (PI) therapy may not be accounted for solely by enhanced viral suppression, implying that PI may directly affect T cell survival. Since HIV T cell depletion is associated with enhanced apoptosis, we analyzed the effect of PIs on T cell apoptosis. In vitro treatment of peripheral blood lymphocytes (PBLs) from HIV-infected but untreated patients with reverse transcriptase inhibitors (RTIs) does not alter apoptosis, whereas PI treatment rapidly reduces CD4⁺ and CD8⁺ T cell apoptosis. In contrast, PI treatment does not alter apoptosis in PBL blasts from HIV-negative patients, or in Jurkat T cells. Consistent with this observation, 8 days of PI therapy in HIV-infected patients does not significantly alter plasma viremia, yet results in significant inhibition of CD4⁺ and CD8⁺ T cell apoptosis. The inhibitory effects of PI on apoptosis have implications concerning the treatment of HIV and its pathogenesis.