Open AccessTackling the problem of HIV drug resistance
Author(s) -
Irene T. Weber,
Robert W. Harrison
Publication year - 2016
Publication title -
postępy biochemii
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.244
H-Index - 15
ISSN - 0032-5422
DOI - 10.18388/pb.2016_26
Subject(s) - drug resistance , genotyping , protease , drug , mutant , human immunodeficiency virus (hiv) , hiv 1 protease , virology , computational biology , genotype , hiv drug resistance , phenotype , biology , medicine , pharmacology , enzyme , genetics , antiretroviral therapy , viral load , gene , biochemistry
The virally-encoded HIV-1 protease is an effective target for antiviral drugs, however, treatment for HIV infections is limited by the prevalence of drug resistant viral mutants. In this review, we describe our three-pronged approach to analyze and combat drugresistance. Understanding the molecular basis for resistance due to protease inhibitors is a key initial step in this approach. This knowledge is being employed for the design of new, improved inhibitors with high affinity for resistant mutants as well as wild type enzyme. In parallel with experimental studies of diverse mutants and inhibitory compounds, we are developing efficient algorithms to predict drug resistance phenotype from genotype data. This approach has important practical applications in the clinic where genotyping is recommended for individuals with new infections.