Performance of an in-house multiplex PCR assay for HIV-1 drug resistance testing - A cheaper alternative

J Virol Methods. 2024 Dec:330:115034. doi: 10.1016/j.jviromet.2024.115034. Epub 2024 Sep 18.

Abstract

Background: Currently, most HIV drug resistance PCR assays amplify the protease-reverse transcriptase (PR-RT) fragment separately from the integrase (IN) fragment. The aim of this study was to develop a multiplex PCR assay that simultaneously amplifies PR-RT and IN fragments for HIV-1 drug-resistance testing.

Methods: The in-house multiplex PCR assay was evaluated on extracted total nucleic acids obtained from the National Health Laboratory Service (NHLS) and Lancet laboratories. Sanger sequencing was performed on amplicons, and HIV-1 drug-resistance mutations (DRMs) were assessed using HIV Stanford drug resistance database.

Results: This study tested 59 patient samples with known HIV-1 viral load and DRM results; 41 from Lancet and 18 from NHLS. In-house multiplex PCR assay detected one or both fragments in most samples but had higher sensitivity for detection of IN fragment (93.2 %) compared to PR-RT fragment (83.1 %). There was 100 % concordance between Lancet assay versus in-house assay sequence data for IN DRMs, but lower concordance with PR-RT (87.0 %). The in-house multiplex PCR assay's precision and reproducibility analysis showed ≥99.9 % sequence similarity and yielded similar DRM results for both PR-RT and IN fragments.

Conclusions: The in-house multiplex PCR assay demonstrated satisfactory performance and higher sensitivity for IN fragment amplification. This could be a cost-effective method for HIV-1 drug resistance testing as both PR-RT and IN fragments are successfully amplified in one reaction in most samples.

Keywords: ARV drug resistance mutations; HIV-1 drug resistance testing; In-house multiplex PCR; Integrase PCR fragment; Protease-reverse transcriptase PCR fragment.

Publication types

  • Evaluation Study

MeSH terms

  • Anti-HIV Agents / pharmacology
  • Drug Resistance, Viral* / genetics
  • HIV Infections* / drug therapy
  • HIV Infections* / virology
  • HIV Integrase* / genetics
  • HIV Protease / genetics
  • HIV Reverse Transcriptase / genetics
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • Humans
  • Microbial Sensitivity Tests / economics
  • Microbial Sensitivity Tests / methods
  • Multiplex Polymerase Chain Reaction* / economics
  • Multiplex Polymerase Chain Reaction* / methods
  • Mutation
  • Sensitivity and Specificity*
  • Viral Load / methods

Substances

  • HIV Integrase
  • Anti-HIV Agents
  • HIV Protease
  • HIV Reverse Transcriptase