Open AccessImportance of minor variants and their detection (ultra‐deep sequencing) in the management of HIV infection
Author(s) -
Paredes R
Publication year - 2012
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.15.6.18309
Subject(s) - medicine , efavirenz , sanger sequencing , human immunodeficiency virus (hiv) , hiv drug resistance , dna sequencing , drug resistance , genotyping , computational biology , bioinformatics , antiretroviral therapy , viral load , virology , biology , genetics , genotype , dna , gene
Sanger genotypic drug resistance assays currently used for routine HIV management often miss low‐frequency drug‐resistant HIV variants, potentially posing patients at risk of antiretroviral treatment failure. Next‐generation sequencing (NGS) technologies allow detection of such minority variants down to approximately 0.5%–1% frequency. They also facilitate interrogating “other” HIV genomic regions like Gag or the RT connection domain, which modulate HIV resistance and are not usually addressed in routine care. Due to the capacity and scalability of NGS platforms, it is even feasible to envision full HIV genome sequencing to inform treatment design at relatively low cost and workload. Although the equipment for NGS remains rather expensive and accurate analysis of NGS still requires comprehensive bioinformatics support, even these barriers are being reduced. The steadfast evolution of NGS platforms is dramatically reducing the cost of genotyping. Open‐source and commercial bioinformatic solutions are automatizing and streamlining analyses and NGS drug resistance data interpretation to the extent that lab technicians without bioinformatics knowledge will soon be able to generate reliable estimates of drug resistance from NGS data on their own. However, despite such impressive advances, the main question remains open: do we need NGS for HIV management? In this presentation, we will review the evidence supporting (or not) NGS for HIV clinical management. We will argue that, on one hand, detection of minority variants may further improve the outcomes of first‐line efavirenz or nevirapine‐based ART, may help design more effective salvage ART regimens, and may improve clinical outcomes to CCR5 antagonists. On the other hand, although well‐powered studies are generally lacking, detection of minority variants does not seem to modify the outcomes of first‐line ART including higher genetic barrier drugs such as second‐generation NNRTIs, protease or integrase inhibitors. We will then discuss the relationship between minority variants and ART adherence and will end by summarizing the main challenges faced by NGS to reach routine HIV clinical management.