Sensitive HIV-1 DNA Pol Next-Generation Sequencing for the Characterisation of Archived Antiretroviral Drug Resistance

Viruses. 2023 Aug 25;15(9):1811. doi: 10.3390/v15091811.

Abstract

Modern HIV-1 treatment effectively suppresses viral amplification in people living with HIV. However, the persistence of HIV-1 DNA as proviruses integrated into the human genome remains the main barrier to achieving a cure. Next-generation sequencing (NGS) offers increased sensitivity for characterising archived drug resistance mutations (DRMs) in HIV-1 DNA for improved treatment options. In this study, we present an ultra-sensitive targeted PCR assay coupled with NGS and a robust pipeline to characterise HIV-1 DNA DRMs from buffy coat samples. Our evaluation supports the use of this assay for Pan-HIV-1 analyses with reliable detection of DRMs across the HIV-1 Pol region. We propose this assay as a new valuable tool for monitoring archived HIV-1 drug resistance in virologically suppressed individuals, especially in clinical trials investigating novel therapeutic approaches.

Trial registration: ClinicalTrials.gov NCT04337450.

Keywords: HIV-1; HIV-1 DNA; NGS; drug resistance; provirus; sanger.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • Anti-Retroviral Agents / therapeutic use
  • Drug Resistance, Viral / genetics
  • Genotype
  • HIV Infections* / drug therapy
  • HIV Seropositivity*
  • HIV-1* / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mutation

Substances

  • Anti-HIV Agents
  • Anti-Retroviral Agents

Associated data

  • ClinicalTrials.gov/NCT04337450