Genetic and antiretroviral drug resistance mutations analysis of reverse transcriptase and protease gene from Pakistani people living with HIV-1
Siddiqui D. Badar U. Javaid M. Farooqui N. Shah S.A. Iftikhar A. Sultan F. Mir F. Furqan S. Mahmood S.F. Abidi S.H.
August 2023Public Library of Science
PLoS ONE
2023#18Issue 8 August
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 countrys 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.
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Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan
Department of Genetics, University of Karachi, Karachi, Pakistan
Medical College, Aga Khan University, Karachi, Pakistan
Bridge Consultants Foundation, Karachi, Pakistan
Shaukat Khanum Memorial Hospital and Research Centre, Lahore, Pakistan
Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
National AIDS Control Program, Ministry of Health, Islamabad, Pakistan
Department of Medicine, Aga Khan University, Karachi, Pakistan
Department of Biomedical Sciences, Nazarbayev University School of Medicine, Astana, Kazakhstan
Department of Biological and Biomedical Sciences
Department of Genetics
Medical College
Bridge Consultants Foundation
Shaukat Khanum Memorial Hospital and Research Centre
Department of Pediatrics and Child Health
National AIDS Control Program
Department of Medicine
Department of Biomedical Sciences
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