Isolation of drug-resistant mutant HIV variants using tissue culture drug selection

Abstract

The life cycle of HIV-1 can be affected in different manners by the various classes of antiviral agents. Genetic heterogeneity is a characteristic of this virus, which contributes significantly to the ability of the virus to generate mutations which overcome the efficacy of the drug therapy. The selection of drug resistant mutants in vitro can be readily accomplished by maintaining the virus in a state of sub-optimal growth, regulated by slowly increasing the amount of drug pressure applied. This technique is thought to mimic the consequences of drug therapy in patients. Therefore, in this way, novel compounds can be assessed for their selection profile in order to preview the likelihood of emergence of HIV-1 drug resistance in future clinical trials. In addition, combinations of drugs can be investigated in the same manner. © 2009 Humana Press.