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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Virology
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1482348

Low Prevalence of Archived Integrase Strand Transfer Inhibitors Resistance Associated Mutations in Botswana Before the Roll Out of Dolutegravir Based First Line Antiretroviral Therapy

Provisionally accepted
Dorcas Maruapula Dorcas Maruapula 1Doreen Ditshwanelo Doreen Ditshwanelo 1Marea N Pema Marea N Pema 1Ontlametse T. Bareng Ontlametse T. Bareng 1,2Wonderful T Choga Wonderful T Choga 1,2Natasha O. Moraka Natasha O. Moraka 1,2Patrick T. Mokgethi Patrick T. Mokgethi 3Kaelo K. Seatla Kaelo K. Seatla 1Catherine K. Koofhethile Catherine K. Koofhethile 1,4Boitumelo L. Zuze Boitumelo L. Zuze 1,2Tendani Gaolathe Tendani Gaolathe 1Molly Pretorius-Holme Molly Pretorius-Holme 4Kebaneilwe Lebani Kebaneilwe Lebani 5Joseph Makhema Joseph Makhema 1,4Vlad Novitsky Vlad Novitsky 1Roger Shapiro Roger Shapiro 1,4Shahin Lockman Shahin Lockman 1,4,6Lucie Abeler-Dorner Lucie Abeler-Dorner 7Sikhulile Moyo Sikhulile Moyo 1,4,8Simani Gaseitsiwe Simani Gaseitsiwe 1,4*
  • 1 Botswana Harvard Health Partnership, Gaborone, Botswana
  • 2 Faculty of Health Sciences, Medical Laboratory Sciences, University of Botswana, Gaborone, Botswana
  • 3 Department of Biological Sciences, University of Botswana, Gaborone, Botswana
  • 4 Department of Immunology and Infectious Diseases, Harvard University T.H Chan School of Public Health, Boston, United States
  • 5 Department of Biological Sciences and Biotechnology, Botswana International University of Science and Technology, Palapye, Central District, Botswana
  • 6 Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States
  • 7 The PANGEA consortium, Phylogenetics and Networks for Generalized Epidemics in Africa, London, United Kingdom
  • 8 School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

The final, formatted version of the article will be published soon.

    Background: We 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. Methods: We used the Stanford University HIV drug resistance database to analyze INSTIresistance 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 2013-2018. A total of 5144 HIV-1 proviral DNA sequences were included in our analysis; 1281 sequences were from antiretroviral therapy (ART)-naïve individuals and 3863 sequences were from non-nucleoside reverse transcriptase inhibitor (NNRTI) ART-experienced individuals. None of the sequences were from DTG-ART experienced participants. Results: The 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% (21/1281) and 0.93% (36/3863) in ART-experienced individuals. Major INSTI-RAMs detected in ART-naïve individuals were E138K(2/1281; 0.16%), G140R (8/1281;0.62%), E92G (2/1281;0.16%), R263K (5/1281; 0.4%), N155H (1/1281; 0.08%), P145S (1/1281;0.008%). Among the ART-experienced individuals, major INSTI RAMs detected were E138K (4/3863; 0.10%), G140R (25/3863;0.65%), G118R (2/3863, 0.05%), R263K (4/3863, 0.10%), T66I (1/3863;0.03%), E138K+G140R (1/3863, 0.03%|), G140R + R263K (1/3863, 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.The 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 ARTexperienced individuals. Ongoing surveillance of INSTI DRMs in Botswana will allow for reassessment of INSTI resistance risk following nationwide DTG rollout.

    Keywords: Botswana, HIV, Integrase strand transfer inhibitor (INSTI), HIV drug resistance mutations (DRMs), Antiretroviral therapy (ART)

    Received: 18 Aug 2024; Accepted: 07 Oct 2024.

    Copyright: © 2024 Maruapula, Ditshwanelo, N Pema, Bareng, T Choga, Moraka, Mokgethi, Seatla, Koofhethile, Zuze, Gaolathe, Pretorius-Holme, Lebani, Makhema, Novitsky, Shapiro, Lockman, Abeler-Dorner, Moyo and Gaseitsiwe. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Simani Gaseitsiwe, Botswana Harvard Health Partnership, Gaborone, Botswana

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