학술논문
Doravirine-associated resistance mutations in antiretroviral therapy naïve and experienced adults with HIV-1 subtype C infection in Botswana.
Document Type
Academic Journal
Author
Bareng OT; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Medical Sciences, Faculty of Allied Health Professions, University of Botswana, Gaborone, Botswana.; Seselamarumo S; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana.; Seatla KK; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Medical Sciences, Faculty of Allied Health Professions, University of Botswana, Gaborone, Botswana.; Choga WT; 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.; Bakae B; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.; Maruapula D; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana.; Kelentse N; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Medical Sciences, Faculty of Allied Health Professions, University of Botswana, Gaborone, Botswana.; Moraka NO; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Division of Medical Virology, Stellenbosch University, Cape Town, South Africa.; Mokaleng B; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Medical Sciences, Faculty of Allied Health Professions, University of Botswana, Gaborone, Botswana.; Mokgethi PT; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana.; Ditlhako TR; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.; Pretorius-Holme M; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Mbulawa MB; Ministry of Health, Republic of Botswana, Gaborone, Botswana.; Lebelonyane R; Ministry of Health, Republic of Botswana, Gaborone, Botswana.; Bile EC; FHI 360, Department of Clinical Sciences, Durham, North Carolina, USA.; Gaolathe T; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.; Shapiro R; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Makhema JM; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Lockman S; 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.; Essex M; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Novitsky V; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Mpoloka SW; Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana.; Moyo S; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.; Gaseitsiwe S; 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.
Source
Publisher: Published by Elsevier Ltd. on behalf of International Society of Chemotherapy for Infection and Cancer Country of Publication: Netherlands NLM ID: 101622459 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-7173 (Electronic) Linking ISSN: 22137165 NLM ISO Abbreviation: J Glob Antimicrob Resist Subsets: MEDLINE
Subject
Language
English
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.
Competing Interests: Declaration of Competing Interest None declared.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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.
Competing Interests: Declaration of Competing Interest None declared.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)