The emergence and spread of HIV drug resistance (DR) is threatening the
global advances gained from antiretroviral therapy (ART) in suppressing HIV-1
infection and reducing AIDS-related morbidity and mortality over the last decade.
Next-generation sequencing (NGS) has fundamentally altered the landscape of HIV-1
DR testing through widely and deep sequencing in a much more cost effective and
rapid manner. NGS is improving our ability to understand, diagnose, and prevent HIV
DR by accurately identifying low abundant (< 20%) HIV DR variants (LADRVs)
relevant to ART outcomes. NGS has been increasingly adopted by research and clinical
laboratories for research, surveillance, and clinical monitoring of HIV DR in the last
decade. However, NGS faces a number of limitations in its application of HIV DR
testing, including sequencing error management, standardization of NGS procedures
and instruments, external quality assurance of laboratories, computational and
bioinformatics challenges. In this chapter, we will review the HIV-1 genotypic DR
testing methods with the focus on the main NGS platforms available for HIV-1 DR
diagnosis, their characteristics, applications, and limitations. In addition, we will
systematically review LADRV in its distribution, prevalence, mechanism, and impact
on ART outcomes. In the end, we will review the host factors, including the human
leukocyte antigen (HLA), which effects the efficacy of ART.
Keywords: Allele-specific assays, Antiretroviral therapy, Drug resistance, HIV-1, Low
abundant HIV-1 drug-resistant variants, MiSeq, Next-generation Sequencing, Roche 454,
Sanger Sequencing.
