New technology to detect low-level drug-resistant HIV variants

Abstract

Genotypic assays to detect HIV drug resistance are recommended for use in the routine clinical care of HIV-infected persons. Genotypic resistance assays have demonstrated good clinical utility, instructing antiretroviral drug selection and improving therapy outcomes. However, a major limitation of clinically available genotypic assays is the inability to detect low-level drug-resistant variants that exist at low levels within the circulating viral population. Recent data from multiple groups have demonstrated that low-level resistant viral variants are clinically important as they can rapidly grow under drug selection pressure and lead to therapy failure. This article will discuss how ultra-deep sequencing and other new sensitive genotyping technologies can be used to detect low-level drug-resistant HIV variants. It will also address the biological and clinical questions facing the field of HIV genotyping: first, the need to better define the level of sensitivity required to detect drug-resistant variants; second, the effects different resistant variants have on treatment response, and; third, the requirement for genotypic assays to provide information on resistance mutation linkage. Finally, the limitations of the new sensitive genotyping methods will be discussed and how these limitations can lead to discordant results between the different technologies.