scholarly journals Combinative interactions of a human immunodeficiency virus (HIV) Tat antagonist with HIV reverse transcriptase inhibitors and an HIV protease inhibitor.

1994 ◽  
Vol 38 (2) ◽  
pp. 348-352 ◽  
Author(s):  
E V Connell ◽  
M C Hsu ◽  
D D Richman
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Reverse Transcriptase ◽  
Hiv Protease ◽  
Hiv Reverse Transcriptase ◽  
Reverse Transcriptase Inhibitors ◽  
Hiv Protease Inhibitor ◽  
Hiv Tat ◽  
Immunodeficiency Virus

scholarly journals Evaluation of reverse transcriptase and protease inhibitors in two-drug combinations against human immunodeficiency virus replication.

1996 ◽  
Vol 40 (6) ◽  
pp. 1346-1351 ◽  
Author(s):  
C A Deminie ◽  
C M Bechtold ◽  
D Stock ◽  
M Alam ◽  
F Djang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Combination Therapy ◽  
Protease Inhibitor ◽  
Reverse Transcriptase ◽  
Protease Inhibitors ◽  
Nucleoside Analogs ◽  
Drug Combinations ◽  
Hiv Protease ◽  
Human Immunodeficiency Virus Replication ◽  
Immunodeficiency Virus

Current treatments for human immunodeficiency virus (HIV) include both reverse transcriptase and protease inhibitors. Results from in vitro and clinical studies suggest that combination therapy can be more effective than single drugs in reducing viral burden. To evaluate compounds for combination therapy, stavudine (d4T), didanosine (ddI), or BMS-186,318, an HIV protease inhibitor, were combined with other clinically relevant compounds and tested in a T-cell line (CEM-SS) that was infected with HIV-RF or in peripheral blood mononuclear cells infected with a clinical HIV isolate. The combined drug effects were analyzed by the methods described by Chou and Talalay (Adv. Enzyme Regul. 22:27-55, 1984) as well as by Prichard et al. (Antimicrob. Agents Chemother. 37:540-545, 1993). The results showed that combining two nucleoside analogs (d4T-ddI, d4T-zidovudine [AZT], and d4T-zalcitabine [ddC]), two HIV protease inhibitors (BMS-186,318-saquinavir, BMS-186,318-SC-52151, and BMS-186,318-MK-639) or a reverse transcriptase and a protease inhibitor (BMS-186,318-d4T, BMS-186,318-ddI, BMS-186,318-AZT, d4T-saquinavir, d4T-MK-639, and ddI-MK-639) yielded additive to synergistic antiviral effects. In general, analysis of data by either method gave consistent results. In addition, combined antiviral treatments involving nucleoside analogs gave slightly different outcomes in the two cell types, presumably because of a difference in phosphorylation patterns. Importantly, no strong antagonism was observed with the drug combinations studied. These data should provide useful information for the design of clinical trials of combined chemotherapy.

scholarly journals In vitro anti-human immunodeficiency virus (HIV) activity of XM323, a novel HIV protease inhibitor.

1993 ◽  
Vol 37 (12) ◽  
pp. 2606-2611 ◽  
Author(s):  
M J Otto ◽  
C D Reid ◽  
S Garber ◽  
P Y Lam ◽  
H Scarnati ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Hiv Protease ◽  
Hiv Protease Inhibitor ◽  
Immunodeficiency Virus

scholarly journals The human immunodeficiency virus (HIV) protease inhibitor indinavir directly affects the opportunistic fungal pathogenCryptococcus neoformans

2004 ◽  
Vol 42 (2) ◽  
pp. 187-195 ◽  
Author(s):  
Elisabetta Blasi ◽  
Bruna Colombari ◽  
Carlotta Francesca Orsi ◽  
Marcello Pinti ◽  
Leonarda Troiano ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Hiv Protease ◽  
Hiv Protease Inhibitor ◽  
Immunodeficiency Virus

scholarly journals Nucleoside reverse transcriptase inhibitors prevent HIV protease inhibitor-induced atherosclerosis by ubiquitination and degradation of protein kinase C

2006 ◽  
Vol 291 (6) ◽  
pp. C1271-C1278 ◽  
Author(s):  
Emily L. Bradshaw ◽  
Xiang-An Li ◽  
Theresa Guerin ◽  
William V. Everson ◽  
Melinda E. Wilson ◽  
...  
Keyword(s):  
Side Effects ◽  
Protein Kinase ◽  
Protease Inhibitor ◽  
Reverse Transcriptase ◽  
Protease Inhibitors ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Reverse Transcriptase Inhibitors ◽  
Hiv Protease Inhibitor ◽  
Cholesterol Accumulation

HIV protease inhibitors are important pharmacological agents used in the treatment of HIV-infected patients. One of the major disadvantages of HIV protease inhibitors is that they increase several cardiovascular risk factors, including the expression of CD36 in macrophages. The expression of CD36 in macrophages promotes the accumulation of cholesterol, the development of foam cells, and ultimately atherosclerosis. Recent studies have suggested that α-tocopherol can prevent HIV protease inhibitor-induced increases in macrophage CD36 levels. Because of the potential clinical utility of using α-tocopherol to limit some of the side effects of HIV protease inhibitors, we tested the ability of α-tocopherol to prevent ritonavir, a common HIV protease inhibitor, from inducing atherosclerosis in the LDL receptor (LDLR) null mouse model. Surprisingly, α-tocopherol did not prevent ritonavir-induced atherosclerosis. However, cotreatment with the nucleoside reverse transcriptase inhibitors (NRTIs), didanosine or D4T, did prevent ritonavir-induced atherosclerosis. Using macrophages isolated from LDLR null mice, we demonstrated that the NRTIs prevented the upregulation of CD36 and cholesterol accumulation in macrophages. Treatment of LDLR null mice with NRTIs promoted the ubiquitination and downregulation of protein kinase Cα (PKC). Previous studies demonstrated that HIV protease inhibitor activation of PKC was necessary for the upregulation of CD36. Importantly, the in vivo inhibition of PKC with chelerythrine prevented ritonavir-induced upregulation of CD36, accumulation of cholesterol, and the formation of atherosclerotic lesions. These novel mechanistic studies suggest that NRTIs may provide protection from one of the negative side effects associated with HIV protease inhibitors, namely the increase in CD36 levels and subsequent cholesterol accumulation and atherogenesis.

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