Despite the success of potent combination therapy against HIV, a large prop
ortion 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 d
rug 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. Wh
ereas genotyping detects resistance-conferring mutations in the HIV reverse
transcriptase and protease genes, the recombinant virus assay is a newly d
eveloped phenotyping technique which determines drug-susceptibility in a vi
rus culture assay. With both methods, result interpretation remains challen
ging. Retrospective studies and randomized controlled clinical trials suppo
rt the clinical utility of resistance testing in the setting of treatment f
ailure. The optimal applications of resistance testing in a variety of othe
r clinical settings remain to be defined.