Genotypic resistance testing in routine clinical care

Abstract

Genotypic resistance testing has become part of routine clinical management of HIV-infected patients. Focussing on observational studies, this review looks at recent advances in this area. Translation of the nucleotide sequence generated by the resistance test into clinically useful information remains a major challenge. A recent key development is the availability of therapy optimization tools to predict regimens that are most likely to achieve virological suppression. Standard genotypic resistance testing only examines protease and part of reverse transcriptase; as drugs are licensed to further targets, it has become necessary to expand the repertoire for testing. Traditionally, genotypic testing has not been attempted at viral loads less than 1000 copies/ml, but recent studies indicate that major mutations are often detected at much lower levels. Similarly, various methods have been developed for the detection of minority variants including allele-specific PCR, single-genome sequencing, and ultra-deep sequencing. The technology and interpretation of genotypic resistance tests is in a phase of rapid development. It remains uncertain which of these developments will become part of routine clinical practice.