Decreased HIV-associated T cell apoptosis by HIV protease inhibitors

Antiretroviral treatment of patients infected with HIV results in improveme nts in CD4(+) T cell number. Emerging evidence suggests that some of the im provements in CD4(+) T cell number that occur in response to protease inhib itor (PI) therapy may not be accounted for solely by enhanced viral suppres sion, implying that PI may directly affect T cell survival, Since HIV T cel l depletion is associated with enhanced apoptosis, we analyzed the effect o f PIs on T cell apoptosis, In vitro treatment of peripheral blood lymphocyt es (PBLs) from HIV-infected but untreated patients with reverse transcripta se 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-inf ected patients does not significantly alter plasma viremia, yet results in significant inhibition of CD4(+) and CD8(+) T cell apoptosis, The inhibitor y effects of PI on apoptosis have implications concerning the treatment of HIV and its pathogenesis.