Genetic and antiretroviral drug resistance mutations analysis of reverse transcriptase and protease gene from Pakistani people living with HIV-1.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
29
01
2023
accepted:
08
08
2023
medline:
28
8
2023
pubmed:
24
8
2023
entrez:
24
8
2023
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 37616294
doi: 10.1371/journal.pone.0290425
pii: PONE-D-23-02565
pmc: PMC10449192
doi:
Substances chimiques
Anti-Retroviral Agents
0
Peptide Hydrolases
EC 3.4.-
RNA-Directed DNA Polymerase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0290425Informations de copyright
Copyright: © 2023 Siddiqui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
J Infect Dis. 2006 Sep 15;194 Suppl 1:S51-8
pubmed: 16921473
AIDS Res Hum Retroviruses. 2018 Nov;34(11):1002-1004
pubmed: 29947245
JAMA. 2012 Jul 25;308(4):387-402
pubmed: 22820792
PLoS One. 2020 Mar 2;15(3):e0229275
pubmed: 32119691
Nature. 2019 Jul 30;:
pubmed: 32724203
Med Microbiol Immunol. 2014 Feb;203(1):57-63
pubmed: 24142198
BMC Public Health. 2021 May 27;21(1):1000
pubmed: 34044793
Antivir Ther. 2008;13 Suppl 2:25-36
pubmed: 18575189
Curr HIV Res. 2012 Sep;10(6):532-8
pubmed: 22716105
Science. 1988 Nov 25;242(4882):1168-71
pubmed: 2460924
AIDS Res Hum Retroviruses. 2020 Mar;36(3):248-250
pubmed: 31547672
Top Antivir Med. 2019 Sep/Oct;27(3):111-121
pubmed: 31634862
J Virol. 2007 Oct;81(19):10625-35
pubmed: 17634235
AIDS Res Hum Retroviruses. 2018 Feb;34(2):228-233
pubmed: 29084434
PLoS One. 2009;4(3):e4724
pubmed: 19266092
N Engl J Med. 2002 Aug 8;347(6):385-94
pubmed: 12167680
J Antimicrob Chemother. 2014 Nov;69(11):3095-102
pubmed: 25006240
J Antimicrob Chemother. 2011 Jul;66(7):1467-80
pubmed: 21502281
AIDS. 2011 Jul 17;25(11):1427-30
pubmed: 21516026
Ann Med Surg (Lond). 2022 Nov 02;84:104797
pubmed: 36353449
Clin Infect Dis. 2008 May 15;46(10):1598-600
pubmed: 18419496
J Infect Dis. 2016 Nov 1;214(9):1302-1308
pubmed: 27732929
Infect Genet Evol. 2016 Dec;46:292-307
pubmed: 27587334
AIDS Res Hum Retroviruses. 2007 Apr;23(4):489-97
pubmed: 17506605
Infect Genet Evol. 2017 Oct;54:183-191
pubmed: 28688977
J Pak Med Assoc. 2016 Dec;66(12):1510-1511
pubmed: 27924955
Bioinformatics. 2005 Oct 1;21(19):3797-800
pubmed: 16076886
J Virol. 2004 Apr;78(7):3722-32
pubmed: 15016892
AIDS. 2006 Jun 12;20(9):F9-13
pubmed: 16816549
PLoS One. 2016 Dec 14;11(12):e0167839
pubmed: 27973597
Mol Biol Evol. 2013 May;30(5):1196-205
pubmed: 23420840
J Antimicrob Chemother. 2019 Jul 1;74(7):2024-2029
pubmed: 30989237
PLoS One. 2019 Jan 16;14(1):e0209605
pubmed: 30650082
Virol J. 2011 Apr 23;8:185
pubmed: 21513545
AIDS Res Hum Retroviruses. 2015 Jun;31(6):603-7
pubmed: 25826122
PLoS One. 2011;6(7):e22449
pubmed: 21799857
J Pak Med Assoc. 2019 Aug;69(8):1068-1069
pubmed: 31431753
AIDS Res Hum Retroviruses. 2016 Mar;32(3):220-5
pubmed: 26401720
PLoS One. 2014 Feb 19;9(2):e89291
pubmed: 24586665
Epidemics. 2009 Dec;1(4):230-9
pubmed: 21352769
Antivir Ther. 2009;14(7):1005-9
pubmed: 19918105
Viruses. 2010 Feb;2(2):503-531
pubmed: 21994646
J Antimicrob Chemother. 2013 Jun;68(6):1237-42
pubmed: 23361642
AIDS Res Hum Retroviruses. 2011 Dec;27(12):1277-82
pubmed: 21591988
PLoS One. 2014 Mar 07;9(6):e90845
pubmed: 24609015
J Med Virol. 2016 May;88(5):798-806
pubmed: 26412111
East Mediterr Health J. 2018 Jun 10;24(3):237-242
pubmed: 29908018
AIDS Res Hum Retroviruses. 2007 Oct;23(10):1303-8
pubmed: 17961120
Indian J Med Res. 2005 Apr;121(4):345-55
pubmed: 15817948
Antimicrob Agents Chemother. 2010 Feb;54(2):718-27
pubmed: 19933797
AIDS. 2008 Aug;22 Suppl 2:S67-79
pubmed: 18641472
Arch Virol. 2018 Jan;163(1):33-40
pubmed: 28942522
Clin Infect Dis. 2006 Jun 1;42(11):1608-18
pubmed: 16652319
Nucleic Acids Res. 2003 Jan 1;31(1):298-303
pubmed: 12520007
AIDS Res Hum Retroviruses. 2016 May;32(5):427-33
pubmed: 26651266
Arch Virol. 2020 Apr;165(4):967-972
pubmed: 32060792
Nat Rev Genet. 2004 Jan;5(1):52-61
pubmed: 14708016
Lancet Infect Dis. 2018 Jun;18(6):601
pubmed: 29856353
J Infect Dev Ctries. 2009 Jun 01;3(5):380-91
pubmed: 19759509
Front Microbiol. 2021 Aug 17;12:658186
pubmed: 34484134
Lancet Infect Dis. 2020 Mar;20(3):362-370
pubmed: 31866326