HIV Protease Inhibitors Impact on Apoptosis
- 1 January 2008
- journal article
- review article
- Published by Bentham Science Publishers Ltd. in Medicinal Chemistry
- Vol. 4 (1), 75-79
- https://doi.org/10.2174/157340608783331443
Abstract
Abstract: HIV protease inhibitors are the backbone of HIV therapy. In addition to blocking intracellular HIV protease and dramatically decreasing viral burden, the protease inhibitors also regulate apoptosis. A growing body of data has confirmed the immunomodulatory effects of HIV protease inhibitors which block CD4+ and CD8+ T cell death in models of HIV infection. The mechanism of this apoptosis inhibition is still under active investigation and supported by several proposed hypothesis for how they alter the fate of the cell. More recently, the anti-apoptotic effects of the HIV protease inhibitors has been extended to the non-HIV, non-immune cell, whereby protease inhibitors prevent apoptosis, and disease, in animal models of sepsis, hepatitis and stroke. Interestingly, when HIV protease inhibitors are used at supra-therapeutic concentrations, they exert pro-apoptotic effects. This has been demonstrated in a number of tumor models. Although it is unclear how HIV protease inhibitors can induce apoptosis at increased concentrations, future research will define the targets of the immunomodulation and reveal the full clinical potential of this intriguing class of drugs.Keywords
This publication has 45 references indexed in Scilit:
- HIV protease inhibitor therapy reverses neutrophil apoptosis in AIDS patients by direct calpain inhibitionApoptosis, 2006
- HIV‐1 protease inhibitor induces growth arrest and apoptosis of human prostate cancer LNCaP cells in vitro and in vivo in conjunction with blockade of androgen receptor STAT3 and AKT signalingCancer Science, 2005
- Ritonavir does not inhibit calpain in vitroBiochemical and Biophysical Research Communications, 2005
- HIV Type 1 Protease Inhibitors Enhance Bone Marrow Progenitor Cell Activity in Normal Subjects and in HIV Type 1-Infected PatientsAIDS Research and Human Retroviruses, 2005
- Improved survival in experimental sepsis with an orally administered inhibitor of apoptosisThe FASEB Journal, 2004
- Effect on CD4 T-cell count of replacing protease inhibitors in patients with successful HIV suppressionAIDS, 2004
- Mitochondrion-mediated apoptosis in HIV-1 infectionTrends in Pharmacological Sciences, 2003
- Effects of Antiretroviral Drugs on Human Immunodeficiency Virus Type 1-Induced CD4+T-Cell DeathJournal of Virology, 2002
- Efavirenz plus Zidovudine and Lamivudine, Efavirenz plus Indinavir, and Indinavir plus Zidovudine and Lamivudine in the Treatment of HIV-1 Infection in AdultsThe New England Journal of Medicine, 1999
- Dynamic correlation of apoptosis and immune activation during treatment of HIV infectionCell Death & Differentiation, 1999