Genetic and antiretroviral drug resistance mutations analysis of reverse transcriptase and protease gene from Pakistani people living with HIV-1

PLoS One. 2023 Aug 24;18(8):e0290425. doi: 10.1371/journal.pone.0290425. eCollection 2023.

Abstract

Background: Antiretroviral therapy (ART) effectiveness is compromised by the emergence of HIV drug resistance mutations (DRM) and can lead to the failure of ART. Apart from intrinsic viral factors, non-compliance with drugs and/or the use of sub-optimum therapy can lead to the emergence of DRMs. In Pakistan HIV currently exists as a concentrated epidemic, however, ART coverage is very low, and drug adherence is poor. ART is selected assuming without baseline genotyping. Pakistan has recently seen a rise in treatment failures, but the country's actual burden of DRM is still unknown. In this study, we perform the genetic and drug resistance analysis of the pol gene from Pakistani HIV-positive ART-naïve and ART-experienced individuals.

Methods: In this study, HIV-1 pol was sequenced from 146 HIV-1 positive individuals, divided into ART-naïve (n = 37) and ART-experienced (n = 109). The sequences were also used to determine HIV-1 subtypes, the prevalence of DRM, and pol genetic variability.

Results: DRM analysis identified numerous DRMs against reverse transcriptase inhibitors in both ART-naïve and ART-experienced groups, including a few that are classified as rare. Additionally, the ART-experienced group showed mutations associated with resistance to protease inhibitors. Genetic analysis showed negative selection pressure in both groups, but a higher rate of evolution in the ART-naïve group.

Conclusion: High prevalence of DRMs, especially against previous first-line treatment in ART- naïve and the accumulation of DRMs in ART-experienced groups is concerning and warrants that a more extensive DRM survey be carried out to inform first-line and second-line ART regimen recommendations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Retroviral Agents* / pharmacology
  • Anti-Retroviral Agents* / therapeutic use
  • Drug Resistance, Multiple, Viral* / genetics
  • Genes, pol* / genetics
  • HIV Infections* / drug therapy
  • HIV Infections* / genetics
  • HIV Seropositivity
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • Humans
  • Peptide Hydrolases / genetics
  • RNA-Directed DNA Polymerase / genetics
  • South Asian People

Substances

  • Anti-Retroviral Agents
  • Peptide Hydrolases
  • RNA-Directed DNA Polymerase

Supplementary concepts

  • Pakistani people

Grants and funding

This study was funded by the Higher Education Commission grant no. 5217/Sindh/NRPU/R&D/HEC/2016, and Pakistan Science Foundation grant no. PSF/Res/S-AKU/Med (488) awarded to SHA, and the Higher Education Commission grant no. 20-16927/NRPU/R&D/HEC/2021-2020 awarded to SFM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.