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.
Phenix
B N
BN
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ontario, Canada.
Angel
J B
JB
Mandy
F
F
Kravcik
S
S
Parato
K
K
Chambers
K A
KA
Gallicano
K
K
Hawley-Foss
N
N
Cassol
S
S
Cameron
D W
DW
Badley
A D
AD
D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D016049:Didanosine / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006679:HIV Seropositivity; D015497:HIV-1; D006801:Humans; D019169:Jurkat Cells; D019888:Nelfinavir / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology; D019258:Saquinavir / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D019562:Viral Load; D015215:Zidovudine / Q000494:pharmacology
D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019888:Nelfinavir; D016049:Didanosine; D019258:Saquinavir; D019438:Ritonavir