Ex vivo and in vitro effect of human immunodeficiency virus protease inhibitors on neutrophil apoptosis

Polymorphonuclear leukocytes (PMNL) from human immunodeficiency virus (HIV) -infected patients exhibit accelerated apoptosis and impaired functional ac tivity. HIV protease inhibitor-based therapy produces improvements in both acquired and innate immune responses, Ex vivo and in vitro effects of HIV p rotease inhibitors on apoptosis and chemotaxis of PMNL were evaluated. Afte r therapy, there was a rapid and significant decrease of PMNL apoptosis, wh ich correlated with increased chemotactic function. These findings were fou nd both in patients with immunological and virological response and in cont rol subjects who showed an increase in CD4(+) T cell counts but no concomit ant decline in HIV load, After in vitro treatment with ritonavir or indinav ir, apoptosis of both HIV-infected and -uninfected PMNL markedly decreased and correlated with significant enhancement of chemotaxis, These results su ggest that HIV protease inhibitors may improve the PMNL function by reducin g the apoptosis rate and that this effect may, at least in part, be indepen dent of their antiviral activity.