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. 2025 Mar 3;80(3):767-776.
doi: 10.1093/jac/dkae472.

High prevalence of reverse transcriptase inhibitors associated resistance mutations among people living with HIV on dolutegravir-based antiretroviral therapy in Francistown, Botswana

Ontlametse T Choga  1   2 , Goitseone M Lemogang  1 , Wonderful T Choga  1   2 , Gaonyadiwe Muzanywa  1 , Thembinkosi M Shadreck  1 , Charity Ralegoreng  1 , Dorcas Maruapula  1 , Natasha O Moraka  1   2 , Catherine K Koofhethile  1   3 , Patrick T Mokgethi  1   4 , Kedumetse Seru  1 , Boitumelo J L Zuze  1   2 , Patience Montshosi  1 , Irene Gobe  2 , Modisa S Motswaledi  2 , Rosemary Musonda  1 , Mpaphi B Mbulawa  5 , Joseph Makhema  1   3 , Roger Shapiro  1   3 , Shahin Lockman  1   3   6 , Tony Chebani  5 , Judith Nawa  5 , Lindani Bochena  7 , Sikhulile Moyo  1   3   8   9 , Simani Gaseitsiwe  1   3
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High prevalence of reverse transcriptase inhibitors associated resistance mutations among people living with HIV on dolutegravir-based antiretroviral therapy in Francistown, Botswana

Ontlametse T Choga et al. J Antimicrob Chemother. .

Abstract

Objectives: We assessed HIV-1 drug resistance profiles among people living with HIV (PLWH) with detectable viral load (VL) and on dolutegravir-based antiretroviral therapy (ART) in Botswana.

Methods: The study utilised available 100 residual HIV-1 VL samples from unique PLWH in Francistown who had viraemia at-least 6 months after initiating ART in Botswana's national ART program from November 2023 to January 2024. Viraemia was categorized as low-level viraemia (LLV) (VL: 200-999 copies/mL) or virologic failure (VF) (VL ≥1000 copies/mL). HIV-1 protease, reverse transcriptase and integrase genes were sequenced using an in-house next-generation sequencing Oxford nanopore technology. HIV-1 drug resistance mutations (DRMs) were identified using the HIVdb Program in the Stanford HIV drug resistance database and compared between VL groups.

Results: Among 100 participants, 83.0% were on dolutegravir-based, 10.0% were on non-dolutegravir-based ART and 7.0% had unknown/undocumented ART regimens. Thirty (30%) participants had LLV and 70 (70%) had VF. Among 58 successfully sequenced, 32.8% [95% Confidence Interval (CI): 21.8-46.0] had DRMs to any drug class, 33.3% (4/12) in the LLV group and 32.6% (15/46) in the VF group. Among individuals on dolutegravir-based ART, the overall HIV DRMs were 34.8% (95% CI: 22.7-49.2). By VL groups, 40.0% (95% CI: 16.8-68.7) and 33.3% (95% CI: 20.2-50.0) had DRMs at LLV and VF, respectively.

Conclusions: A high but similar prevalence of any DRMs was observed among individuals with LLV and those with VF on dolutegravir-based therapy. Monitoring DRMs in individuals with detectable VL is crucial for preserving dolutegravir-based ART.

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Figures

Figure 1.
Figure 1.
Selection of study participants.
Figure 2.
Figure 2.
HIV DRMs by drug classes. INSTI, Integrase strand transfer inhibitors; NNRTI, Non-nucleoside reverse transcriptase inhibitors; NRTI, Nucleoside reverse transcriptase inhibitors; PI, Protease inhibitors.
See this image and copyright information in PMC

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