Doravirine-associated resistance mutations in antiretroviral therapy naïve and experienced adults with HIV-1 subtype C infection in Botswana

Ontlametse T Bareng; Sekgabo Seselamarumo; Kaelo K Seatla; Wonderful T Choga; Blessing Bakae; Dorcas Maruapula; Nametso Kelentse; Natasha O Moraka; Baitshepi Mokaleng; Patrick T Mokgethi; Tsotlhe R Ditlhako; Molly Pretorius-Holme; Mpaphi B Mbulawa; Refeletswe Lebelonyane; Ebi Celestin Bile; Tendani Gaolathe; Roger Shapiro; Joseph M Makhema; Shahin Lockman; Max Essex; Vlad Novitsky; Sununguko W Mpoloka; Sikhulile Moyo; Simani Gaseitsiwe

doi:10.1016/j.jgar.2022.08.008

Doravirine-associated resistance mutations in antiretroviral therapy naïve and experienced adults with HIV-1 subtype C infection in Botswana

J Glob Antimicrob Resist. 2022 Dec:31:128-134. doi: 10.1016/j.jgar.2022.08.008. Epub 2022 Aug 13.

Authors

Ontlametse T Bareng¹, Sekgabo Seselamarumo², Kaelo K Seatla¹, Wonderful T Choga³, Blessing Bakae⁴, Dorcas Maruapula², Nametso Kelentse¹, Natasha O Moraka⁵, Baitshepi Mokaleng¹, Patrick T Mokgethi², Tsotlhe R Ditlhako⁴, Molly Pretorius-Holme⁶, Mpaphi B Mbulawa⁷, Refeletswe Lebelonyane⁷, Ebi Celestin Bile⁸, Tendani Gaolathe⁴, Roger Shapiro⁹, Joseph M Makhema⁹, Shahin Lockman¹⁰, Max Essex⁹, Vlad Novitsky⁹, Sununguko W Mpoloka¹¹, Sikhulile Moyo⁹, Simani Gaseitsiwe¹²

Affiliations

¹ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Medical Sciences, Faculty of Allied Health Professions, University of Botswana, Gaborone, Botswana.
² Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana.
³ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
⁴ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
⁵ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Division of Medical Virology, Stellenbosch University, Cape Town, South Africa.
⁶ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
⁷ Ministry of Health, Republic of Botswana, Gaborone, Botswana.
⁸ FHI 360, Department of Clinical Sciences, Durham, North Carolina, USA.
⁹ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
¹⁰ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹¹ Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana.
¹² Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. Electronic address: sgaseitsiwe@bhp.org.bw.

Abstract

Objectives: There are limited data on the prevalence of doravirine (DOR)-associated drug resistance mutations in people with HIV (PWH) in Botswana. This cross-sectional, retrospective study aimed to explore the prevalence of DOR-associated resistance mutations among ART-naïve and -experienced PWH in Botswana enrolled in the population-based Botswana Combination Prevention Project (BCPP).

Methods: A total of 6078 HIV-1C pol sequences were analysed for DOR-associated resistance mutations using the Stanford HIV drug resistance database, and their levels were predicted according to the Stanford DRM penalty scores and resistance interpretation. Virologic failure was defined as HIV-1 RNA load (VL) >400 copies/mL.

Results: Among 6078 PWH, 5999 (99%) had known ART status, and 4529/5999 (79%) were on ART at time of sampling. The suppression rate among ART-experienced was 4517/4729 (96%). The overall prevalence of any DOR-associated resistance mutations was 181/1473 (12.3% [95% confidence interval {CI}: 10.7-14.1]); by ART status: 42/212 (19.8% [95% CI: 14.7-25.4]) among ART-failing individuals (VL ≥400 copies/mL) and 139/1261 (11.0% [95% CI: 9.3-12.9]) among ART-naïve individuals (P < 0.01). Intermediate DOR-associated resistance mutations were observed in 106/1261 (7.8% [95% CI: 6.9-10.1]) in ART-naïve individuals and 29/212 (13.7% [95% CI: 9.4-8.5]) among ART-experienced participants (P < 0.01). High-level DOR-associated resistance mutations were observed in 33/1261 (2.6% [95% CI: 1.8-3.7]) among ART-naïve and 13/212 (6.1% [95% CI: 3.6-10.8]) among ART-failing PWH (P < 0.01). PWH failing ART with at least one EFV/NVP-associated resistance mutation had high prevalence 13/67 (19.4%) of high-level DOR-associated resistance mutations.

Conclusion: DOR-associated mutations were rare (11.0%) among ART-naive PWH but present in 62.7% of Botswana individuals who failed NNRTI-based ART with at least one EFV/NVP-associated resistance mutation. Testing for HIV drug resistance should underpin the use of DOR in PWH who have taken first-generation NNRTIs.

Keywords: Antiretroviral (ART) experienced; Antiretroviral (ART) naive; Botswana; Doravirine; Drug resistance mutations; HIV-1C.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adult
Anti-HIV Agents* / pharmacology
Anti-HIV Agents* / therapeutic use
Botswana
Cross-Sectional Studies
Drug Resistance, Viral / genetics
HIV Infections* / epidemiology
HIV-1* / genetics
Humans
Mutation
Retrospective Studies

Substances

Anti-HIV Agents
doravirine

Abstract

Publication types

MeSH terms

Substances

Grants and funding