High prevalence of pre-treatment and acquired HIV-1 drug resistance mutations among non-citizens living with HIV in Botswana

Patrick T Mokgethi; Wonderful T Choga; Dorcas Maruapula; Natasha O Moraka; Kaelo K Seatla; Ontlametse T Bareng; Doreen D Ditshwanelo; Graceful Mulenga; Terence Mohammed; Pearl M Kaumba; Moses Chihungwa; Tafireyi Marukutira; Sikhulile Moyo; Catherine K Koofhethile; Diana Dickinson; Sununguko W Mpoloka; Simani Gaseitsiwe

doi:10.3389/fmicb.2024.1338191

High prevalence of pre-treatment and acquired HIV-1 drug resistance mutations among non-citizens living with HIV in Botswana

Front Microbiol. 2024 Feb 20:15:1338191. doi: 10.3389/fmicb.2024.1338191. eCollection 2024.

Authors

Patrick T Mokgethi^{1

2}, Wonderful T Choga^{1

3

4}, Dorcas Maruapula¹, Natasha O Moraka^{1

4}, Kaelo K Seatla¹, Ontlametse T Bareng^{1

4}, Doreen D Ditshwanelo¹, Graceful Mulenga¹, Terence Mohammed¹, Pearl M Kaumba^{1

2}, Moses Chihungwa⁵, Tafireyi Marukutira^{1

6

7}, Sikhulile Moyo^{1

8

9

10}, Catherine K Koofhethile^{1

8}, Diana Dickinson⁵, Sununguko W Mpoloka², Simani Gaseitsiwe^{1

8}

Affiliations

¹ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
² Department of Biological Sciences, University of Botswana, Gaborone, Botswana.
³ Center of Epidemic Response and Innovation, Faculty of Data Sciences, Stellenbosch University, Cape Town, South Africa.
⁴ School of Allied Health Professionals, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana.
⁵ Independence Avenue Clinic, Gaborone, Botswana.
⁶ Public Health, Burnet Institute, Melbourne, VIC, Australia.
⁷ Department of Epidemiology, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁸ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
⁹ School of Health Systems and Public Health, University of Pretoria, Pretoria, South Africa.
¹⁰ Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.

Abstract

Background: Approximately 30,000 non-citizens are living with HIV in Botswana, all of whom as of 2020 are eligible to receive free antiretroviral treatment (ART) within the country. We assessed the prevalence of HIV-1 mutational profiles [pre-treatment drug resistance (PDR) and acquired drug resistance (ADR)] among treatment-experienced (TE) and treatment-naïve (TN) non-citizens living with HIV in Botswana.

Methods: A total of 152 non-citizens living with HIV were enrolled from a migrant HIV clinic at Independence Surgery, a private practice in Botswana from 2019-2021. Viral RNA isolated from plasma samples were genotyped for HIV drug resistance (HIVDR) using Sanger sequencing. Major known HIV drug resistance mutations (DRMs) in the pol region were determined using the Stanford HIV Drug Resistance Database. The proportions of HIV DRMs amongst TE and TN non-citizens were estimated with 95% confidence intervals (95% CI) and compared between the two groups.

Results: A total of 60/152 (39.5%) participants had a detectable viral load (VL) >40 copies/mL and these were included in the subsequent analyses. The median age at enrollment was 43 years (Q1, Q3: 38-48). Among individuals with VL > 40 copies/mL, 60% (36/60) were treatment-experienced with 53% (19/36) of them on Atripla. Genotyping had a 62% (37/60) success rate - 24 were TE, and 13 were TN. A total of 29 participants (78.4, 95% CI: 0.12-0.35) had major HIV DRMs, including at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) associated DRM. In TE individuals, ADR to any antiretroviral drug was 83.3% (20/24), while for PDR was 69.2% (9/13). The most frequent DRMs were nucleoside reverse transcriptase inhibitors (NRTIs) M184V (62.1%, 18/29), NNRTIs V106M (41.4%, 12/29), and K103N (34.4%, 10/29). No integrase strand transfer inhibitor-associated DRMs were reported.

Conclusion: We report high rates of PDR and ADR in ART-experienced and ART-naïve non-citizens, respectively, in Botswana. Given the uncertainty of time of HIV acquisition and treatment adherence levels in this population, routine HIV-1C VL monitoring coupled with HIVDR genotyping is crucial for long-term ART success.

Keywords: Botswana; HIV-1C; acquired HIV drug resistance (ADR); antiretroviral therapy (ART); drug resistance mutations (DRMs); non-citizens; pre-treament drug resistance (PDR).

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. PM, NM, OB were supported by the Fogarty International Center at the US National Institutes of Health (D43 TW009610). SMo is partially supported by the Fogarty International Center at the US National Institutes of Health (1 K43 TW 012350-01). SG, SMo, CK and WC were partially supported by a G11 grant funded by the NIH Fogarty International Centre (G11 TW012503-01). SMo, DoD, and OB were supported by the Trials of Excellence in Southern Africa (TESA III), which is part of the EDCTP2 program supported by the European Union (CSA2020NoE-3104 TESAIII CSA2020NoE). SG, SMo, WC,CK and NM are partly supported through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE 2.0) from the Bill and Melinda Gates Foundation (INV-033558). The views expressed in this publication are those of the authors and not necessarily those of the funding agencies. The funders had no role in the study design, data collection, decision to publish, or preparation of this manuscript.