Limited emergence of resistance to integrase strand transfer inhibitors (INSTIs) in ART-experienced participants failing dolutegravir-based antiretroviral therapy: a cross-sectional analysis of a Northeast Nigerian cohort.
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
02 08 2023
02 08 2023
Historique:
received:
26
02
2023
accepted:
30
05
2023
medline:
3
8
2023
pubmed:
27
6
2023
entrez:
27
6
2023
Statut:
ppublish
Résumé
Due to the high prevalence of resistance to NNRTI-based ART since 2018, consolidated recommendations from the WHO have indicated dolutegravir as the preferred drug of choice for HIV treatment globally. There is a paucity of resistance outcome data from HIV-1 non-B subtypes circulating across West Africa. We characterized the mutational profiles of persons living with HIV from a cross-sectional cohort in North-East Nigeria failing a dolutegravir-based ART regimen. WGS of plasma samples collected from 61 HIV-1-infected participants following virological failure of dolutegravir-based ART were sequenced using the Illumina platform. Sequencing was successfully completed for samples from 55 participants. Following quality control, 33 full genomes were analysed from participants with a median age of 40 years and median time on ART of 9 years. HIV-1 subtyping was performed using SNAPPy. Most participants had mutational profiles reflective of exposure to previous first- and second-line ART regimens comprised NRTIs and NNRTIs. More than half of participants had one or more drug resistance-associated mutations (DRMs) affecting susceptibility to NRTIs (17/33; 52%) and NNRTIs (24/33; 73%). Almost a quarter of participants (8/33; 24.4%) had one or more DRMs affecting tenofovir susceptibility. Only one participant, infected with HIV-1 subtype G, had evidence of DRMs affecting dolutegravir susceptibility-this was characterized by the T66A, G118R, E138K and R263K mutations. This study found a low prevalence of resistance to dolutegravir; the data are therefore supportive of the continual rollout of dolutegravir as the primary first-line regimen for ART-naive participants and the preferred switch to second-line ART across the region. However, population-level, longer-term data collection on dolutegravir outcomes are required to further guide implementation and policy action across the region.
Sections du résumé
BACKGROUND
Due to the high prevalence of resistance to NNRTI-based ART since 2018, consolidated recommendations from the WHO have indicated dolutegravir as the preferred drug of choice for HIV treatment globally. There is a paucity of resistance outcome data from HIV-1 non-B subtypes circulating across West Africa.
AIMS
We characterized the mutational profiles of persons living with HIV from a cross-sectional cohort in North-East Nigeria failing a dolutegravir-based ART regimen.
METHODS
WGS of plasma samples collected from 61 HIV-1-infected participants following virological failure of dolutegravir-based ART were sequenced using the Illumina platform. Sequencing was successfully completed for samples from 55 participants. Following quality control, 33 full genomes were analysed from participants with a median age of 40 years and median time on ART of 9 years. HIV-1 subtyping was performed using SNAPPy.
RESULTS
Most participants had mutational profiles reflective of exposure to previous first- and second-line ART regimens comprised NRTIs and NNRTIs. More than half of participants had one or more drug resistance-associated mutations (DRMs) affecting susceptibility to NRTIs (17/33; 52%) and NNRTIs (24/33; 73%). Almost a quarter of participants (8/33; 24.4%) had one or more DRMs affecting tenofovir susceptibility. Only one participant, infected with HIV-1 subtype G, had evidence of DRMs affecting dolutegravir susceptibility-this was characterized by the T66A, G118R, E138K and R263K mutations.
CONCLUSIONS
This study found a low prevalence of resistance to dolutegravir; the data are therefore supportive of the continual rollout of dolutegravir as the primary first-line regimen for ART-naive participants and the preferred switch to second-line ART across the region. However, population-level, longer-term data collection on dolutegravir outcomes are required to further guide implementation and policy action across the region.
Identifiants
pubmed: 37367727
pii: 7208628
doi: 10.1093/jac/dkad195
pmc: PMC10393879
doi:
Substances chimiques
dolutegravir
DKO1W9H7M1
Heterocyclic Compounds, 3-Ring
0
Oxazines
0
Pyridones
0
HIV Integrase Inhibitors
0
Integrases
EC 2.7.7.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2000-2007Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI147331
Pays : United States
Investigateurs
Lucie Abeler-Dörner
(L)
Helen Ayles
(H)
David Bonsall
(D)
Rory Bowden
(R)
Vincent Calvez
(V)
Max Essex
(M)
Sarah Fidler
(S)
Christophe Fraser
(C)
Kate Grabowski
(K)
Tanya Golubchik
(T)
Ravindra Gupta
(R)
Richard Hayes
(R)
Joshua Herbeck
(J)
Joseph Kagaayi
(J)
Pontiano Kaleebu
(P)
Jairam Lingappa
(J)
Sikhulile Moyo
(S)
Vladimir Novitsky
(V)
Thumbi Ndung'u
(T)
Deenan Pillay
(D)
Thomas Quinn
(T)
Andrew Rambaut
(A)
Oliver Ratmann
(O)
Janet Seeley
(J)
Deogratius Ssemwanga
(D)
Frank Tanser
(F)
Maria Wawer
(M)
Myron Cohen
(M)
Tulio D'Oliveira
(T)
Ann Dennis
(A)
Max Essex
(M)
Sarah Fidler
(S)
Dan Frampton
(D)
Christophe Fraser
(C)
Tanya Golubchik
(T)
Richard Hayes
(R)
Josh Herbeck
(J)
Anne Hoppe
(A)
Pontiano Kaleebu
(P)
Paul Kellam
(P)
Cissy Kityo
(C)
Andrew Leigh-Brown
(A)
Jairam Lingappa
(J)
Vladimir Novitsky
(V)
Nick Paton
(N)
Deenan Pillay
(D)
Tom Quinn
(T)
Oliver Ratmann
(O)
Deogratius Ssemwanga
(D)
Frank Tanser
(F)
Maria Wawer
(M)
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.
Références
Clin Infect Dis. 2018 May 17;66(11):1794-1797
pubmed: 29293895
AIDS. 2023 Feb 1;37(2):333-339
pubmed: 36541644
Lancet Infect Dis. 2017 Mar;17(3):296-304
pubmed: 27914856
J Antimicrob Chemother. 2022 Feb 2;77(2):474-482
pubmed: 34741609
J Antimicrob Chemother. 2021 Apr 13;76(5):1277-1285
pubmed: 33501504
Clin Infect Dis. 2014 Apr;58(7):1023-6
pubmed: 24352348
Lancet Infect Dis. 2018 Mar;18(3):346-355
pubmed: 29198909
Lancet HIV. 2020 Oct;7(10):e677-e687
pubmed: 33010241
J Infect Dis. 2020 Sep 1;222(7):1108-1116
pubmed: 31774913
EClinicalMedicine. 2020 Jan 05;18:100231
pubmed: 31922120
Lancet Infect Dis. 2009 Jul;9(7):409-17
pubmed: 19555900
mBio. 2022 Jun 28;13(3):e0026922
pubmed: 35446121
South Afr J HIV Med. 2019 Jun 27;20(1):885
pubmed: 31308964
Nat Commun. 2020 Dec 1;11(1):5922
pubmed: 33262331
EClinicalMedicine. 2019 Mar 18;9:26-34
pubmed: 31143879
J Antimicrob Chemother. 2019 Oct 1;74(10):3011-3015
pubmed: 31299067
AIDS Rev. 2003 Jan-Mar;5(1):52-61
pubmed: 12875108
Lancet. 2012 Oct 6;380(9849):1250-8
pubmed: 22828485
J Infect Dis. 2022 Feb 1;225(3):364-366
pubmed: 34282844
Lancet HIV. 2019 Feb;6(2):e72-e73
pubmed: 30503326
Open Forum Infect Dis. 2018 Dec 12;6(1):ofy329
pubmed: 30648124
Lancet. 2019 Jan 12;393(10167):143-155
pubmed: 30420123
Mol Biol Evol. 2018 Mar 1;35(3):719-733
pubmed: 29186559
J Acquir Immune Defic Syndr. 2009 Oct 1;52(2):228-34
pubmed: 19644383
Lancet HIV. 2020 Oct;7(10):e666-e676
pubmed: 33010240
J Antimicrob Chemother. 2020 Jun 1;75(6):1575-1579
pubmed: 32105319
J Antimicrob Chemother. 2016 Jul;71(7):1948-53
pubmed: 27029845
South Afr J HIV Med. 2020 Jul 02;21(1):1062
pubmed: 32832110
Antimicrob Agents Chemother. 2023 May 17;67(5):e0138622
pubmed: 37071019
AIDS Res Hum Retroviruses. 2018 May;34(5):404-414
pubmed: 29353487
J Infect Dis. 2006 Sep 1;194(5):651-60
pubmed: 16897664
Cell Host Microbe. 2019 Jul 10;26(1):48-60
pubmed: 31295424
J Antimicrob Chemother. 2019 Nov 1;74(11):3135-3149
pubmed: 31280314
Mol Biol Evol. 2020 May 1;37(5):1530-1534
pubmed: 32011700
J Infect Dis. 2013 Jun 15;207 Suppl 2:S49-56
pubmed: 23687289
J Infect Dis. 2013 Jun 15;207 Suppl 2:S78-84
pubmed: 23687293
mBio. 2020 Nov 3;11(6):
pubmed: 33144375
J Antimicrob Chemother. 2019 Mar 1;74(3):739-745
pubmed: 30476165
Clin Infect Dis. 2017 Apr 15;64(8):1006-1016
pubmed: 28329393
Lancet HIV. 2020 Sep;7(9):e620-e628
pubmed: 32890497
J Antimicrob Chemother. 2014 Oct;69(10):2733-40
pubmed: 24917583
J Clin Microbiol. 2020 Sep 22;58(10):
pubmed: 32669382
J Acquir Immune Defic Syndr. 2022 May 1;90(1):88-96
pubmed: 35090157
AIDS Res Hum Retroviruses. 2011 Jan;27(1):71-80
pubmed: 20964479
Clin Infect Dis. 2018 Jun 1;66(12):1846-1857
pubmed: 29272346
Virus Evol. 2019 Nov 19;5(2):vez050
pubmed: 31768265
BMC Infect Dis. 2017 Mar 16;17(1):215
pubmed: 28302065
EBioMedicine. 2020 May;55:102779
pubmed: 32408111
Lancet Infect Dis. 2016 May;16(5):565-575
pubmed: 26831472
PLOS Glob Public Health. 2022 Oct 11;2(10):e0000826
pubmed: 36962573
Medicine (Baltimore). 2019 Aug;98(32):e16813
pubmed: 31393412
J Antimicrob Chemother. 2020 May 1;75(5):1290-1293
pubmed: 32065630
AIDS. 2021 Dec 15;35(Suppl 2):S173-S182
pubmed: 34848584