Structure-based phenotyping predicts HIV-1 protease inhibitor resistance

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HIV-1 protease mutations and protease inhibitor cross-resistance.

The effects of many protease inhibitor (PI)-selected mutations on the susceptibility to individual PIs are unknown. We analyzed in vitro susceptibility test results on 2,725 HIV-1 protease isolates. More than 2,400 isolates had been tested for susceptibility to fosamprenavir, indinavir, nelfinavir, and saquinavir; 2,130 isolates had been tested for susceptibility to lopinavir; 1,644 isolates ha...

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Protease inhibitors (PIs) were initially introduced in the mid-1990s and when used in combination with nucleoside reverse transcriptase inhibitors (NRTI), ushered in the era of highly active antiretroviral therapy (HAART). These agents dramatically altered the treatment of HIV infection, enabling suppression of viral replication to undetectable levels and significantly impacting disease progres...

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A Novel Substrate-Based HIV-1 Protease Inhibitor Drug Resistance Mechanism

BACKGROUND HIV protease inhibitor (PI) therapy results in the rapid selection of drug resistant viral variants harbouring one or two substitutions in the viral protease. To combat PI resistance development, two approaches have been developed. The first is to increase the level of PI in the plasma of the patient, and the second is to develop novel PI with high potency against the known PI-resist...

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ژورنال

عنوان ژورنال: Protein Science

سال: 2003

ISSN: 0961-8368,1469-896X

DOI: 10.1110/ps.0301103