Resistance of human immunodeficiency virus type 1 to reverse transcriptaseand protease inhibitors: genotypic and phenotypic testing

Treatment of HIV-l-infected persons with antiretroviral drugs including rev erse transcriptase (RT) and protease inhibitors has significantly reduced t he rate of HIV and AIDS-related morbidity and mortality. However, these tre atments can select for drug-resistant viruses which are associated with poo r virologic responses to the antiretroviral therapies and loss of clinical benefit. Drug resistance is conferred by single or several amino acid chang es in the pol gene. These mutations can be classified as primary when they directly confer reduced drug susceptibility, or secondary when their influe nce is primarily on replication capabilities of resistant viruses. Both gen otypic and phenotypic methods are used for drug resistance testing. Genotyp ic assays detect resistance-related mutations by sequence analysis or point mutations assays. Phenotypic testing measures drug susceptibility of patie nt-derived viruses in culture assays. Viruses can be conventionally isolate d from peripheral blood lymphocytes, or generated more rapidly through reco mbination of plasma-derived RT/protease sequences and modified HIV-1 vector s. Phenotypic testing provides direct evidence of resistance, is easy to in terpret, but is laborious and expensive. In contrast, genotypic testing pro vides indirect evidence of resistance, is relatively faster and cheaper, bu t some complex mutation patterns may be difficult to interpret. Non-culture based phenotypic assays that measure susceptibility of RT activity in plas ma to RT inhibitors have been described recently, and provide new tools for rapid phenotypic testing. Resistance testing is currently recommended to h elp guide the choice of new regimens after treatment failure and for guidin g therapy in pregnant women. (C) 2001 Elsevier Science B.V. All rights rese rved.