Antiretroviral resistance in clinical practice

Despite the success of potent combination therapy against HIV, a large proportion of patients experiences treatment failure. Due to the high degree of plasticity of the HIV genome, ongoing virus replication in the presence of drug pressure will result in the selection of virus mutants with reduced drug susceptibility. As a result, antiretroviral drug-resistance is a common denominator in treatment failure. Two methods, genotyping and phenotyping, are commercially available for measuring resistance in clinical samples. Whereas genotyping detects resistance-conferring mutations in the HIV reverse transcriptase and protease genes, the recombinant virus assay is a newly developed phenotyping technique which determines drug-susceptibility in a virus culture assay. With both methods, result interpretation remains challenging. Retrospective studies and randomized controlled clinical trials support the clinical utility of resistance testing in the setting of treatment failure. The optimal applications of resistance testing in a variety of other clinical settings remain to be defined.