Back to Search Start Over

Low prevalence of archived integrase strand transfer inhibitors resistance associated mutations in Botswana before the roll out of dolutegravir based first line antiretroviral therapy

Low prevalence of archived integrase strand transfer inhibitors resistance associated mutations in Botswana before the roll out of dolutegravir based first line antiretroviral therapy

Authors :
Dorcas Maruapula
Doreen Ditshwanelo
Marea N. Pema
Ontlametse T. Bareng
Wonderful T. Choga
Natasha O. Moraka
Patrick T. Mokgethi
Kaelo K. Seatla
Catherine K. Koofhethile
Boitumelo J. Zuze
Tendani Gaolathe
Molly Pretorius-Holme
Kebaneilwe Lebani
Joseph Makhema
Vlad Novitsky
Roger Shapiro
Shahin Lockman
Sikhulile Moyo
Simani Gaseitsiwe
Source :
Frontiers in Microbiology, Vol 15 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

BackgroundWe evaluated the prevalence of archived proviral drug resistance mutations (DRMs) associated with resistance to integrase strand transfer inhibitors (INSTIs) shortly before Botswana transitioned in 2016 to using dolutegravir (DTG)-based antiretroviral treatment in first-line regimens.MethodsWe used the Stanford University HIV drug resistance database to analyze INSTI-resistance associated mutations (RAMs) in a large representative population-based cohort of adults recruited in 30 geographically dispersed communities as part of the Botswana Combination Prevention Project (BCPP) cohort from 2013 to 2018. A total of 5,144 HIV-1 proviral DNA sequences were included in our analysis; 1,281 sequences were from antiretroviral therapy (ART)-naïve individuals and 3,863 sequences were from non-nucleoside reverse transcriptase inhibitor (NNRTI) ART-experienced individuals. None of the sequences were from DTG-ART experienced participants.ResultsThe overall prevalence of major INSTIs DRMs was 1.11% (95% CI 0.82–1.39%). The prevalence of INSTI DRMs in ART-naïve individuals was 1.64% (21/1,281) and 0.93% (36/3,863) in ART-experienced individuals. Major INSTI-RAMs detected in ART-naïve individuals were E138K (2/1,281; 0.16%), G140R (8/1,281;0.62%), E92G (2/1,281;0.16%), R263K (5/1,281; 0.4%), N155H (1/1,281; 0.08%), P145S (1/1,281;0.008%). Among the ART-experienced individuals, major INSTI RAMs detected were E138K (4/3,863; 0.10%), G140R (25/3,863;0.65%), G118R (2/3,863, 0.05%), R263K (4/3,863, 0.10%), T66I (1/3,863;0.03%), E138K + G140R (1/3,863, 0.03%|), G140R + R263K (1/3,863, 0.03%). High-level resistance to cabotegravir (CAB), elvitegravir (EVG), and raltegravir (RAL) was detected in 0.70, 0.16 and 0.06% of the individuals, respectively. Notably, bictegravir (BIC) and dolutegravir (DTG) showed no high-level resistance.ConclusionThe overall prevalence of archived INSTI RAMs in Botswana was low prior to transitioning to first-line DTG-based ART regimens, and did not differ between ART-naïve and ART-experienced individuals. Ongoing surveillance of INSTI DRMs in Botswana will allow for re-assessment of INSTI resistance risk following nationwide DTG rollout.

Details

Language :
English
ISSN :
1664302X
Volume :
15
Database :
Directory of Open Access Journals
Journal :
Frontiers in Microbiology
Publication Type :
Academic Journal
Accession number :
edsdoj.38caff23dfd94972b28750adba2eaf3b
Document Type :
article
Full Text :
https://doi.org/10.3389/fmicb.2024.1482348