학술논문
Pharmaco-virological outcomes and genotypic resistance profiles among children and adolescents receiving a DTG-based regimen in Togo.
Document Type
Academic Journal
Author
Konu YR; Département de Santé Publique, Université de Lomé, Faculté des Sciences de la Santé, Lomé, Togo.; Centre Africain de Recherche en Epidémiologie et en Santé Publique (CARESP), Lomé, Togo.; Takassi E; Service de pédiatrie, CHU Sylvanus Olympio, Université de Lomé, 05 BP 846 Lomé, Togo.; Peytavin G; Service de Pharmacologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.; Dapam N; Espoir Vie Togo, Lomé, Togo.; Damond F; Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.; Oumarou WA; Centre Africain de Recherche en Epidémiologie et en Santé Publique (CARESP), Lomé, Togo.; Zaidi M; Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.; Franco-Yusti AM; Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.; Dagnra CA; Université de Lomé, Centre de Biologie Moléculaire et d'Immunologie, Lomé, Togo.; Le Hingrat Q; Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.; Coppée R; Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.; Descamps D; Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.; Diallo FBT; Togo Office, World Health Organization (WHO), Lomé, Togo.; Ekouevi DK; Centre Africain de Recherche en Epidémiologie et en Santé Publique (CARESP), Lomé, Togo.; Faculty of Health Sciences, Department of Public Health, University of Lomé, Center for Training and Research in Public Health, Lomé, Togo.; Research Institute for Sustainable Development (IRD), University of Bordeaux, INSERM, Bordeaux Population Health Centre, UMR 1219, Bordeaux, France.; Charpentier C; Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.
Source
Publisher: Oxford University Press Country of Publication: United States NLM ID: 9203213 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-6591 (Electronic) Linking ISSN: 10584838 NLM ISO Abbreviation: Clin Infect Dis Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Few data are available on the real-world efficacy of receiving tenofovir-lamivudine-dolutegravir (DTG) as HIV treatment, particularly among young people in West Africa. Here, we evaluated pharmaco-virological outcomes and resistance profiles among Togolese children and adolescents.
Methods: A cross-sectional study was conducted in Lomé, Togo, enrolling antiretroviral-treated people with HIV aged from 18 months to 24 years. Plasma HIV-1 viral load and antiretroviral concentrations were measured. Next-Generation Sequencing (NGS) of protease, Reverse Transcriptase (RT) and integrase was performed on all samples with viral load >200 c/mL. Drug resistance mutations (DRMs) were identified and interpreted using the ANRS-MIE algorithm.
Results: 264 participants were enrolled (median age=17 years), 226 received a DTG-based regimen for a median of 20.5 months. Among them, virological suppression at the 200 c/mL threshold in 80.0% of the participants. Plasma DTG concentrations were adequate (i.e., >640 ng/mL), suboptimal and below the limit of quantification in 74.1%, 6.7% and 19.2% of participants receiving DTG, respectively. Overall, viruses resistant to any of Nucleoside RT Inhibitors, Non-NRTIs, and protease inhibitors were found in 52%, 66% and 1.6% of participants, respectively. A major integrase inhibitor DRM was observed in 9.4% (n=3/32, R263K, E138A-G140A-Q148R, and N155H) of participants with a viral load >200 c/mL.
Conclusions: These first findings in such a large series of adolescents in a low-income country, showed a good virological response of 80% and the presence of an integrase DRM in 9.4% of the virological failures, supporting the need to monitor DTG drug resistance to reduce the risk of resistance acquisition.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Methods: A cross-sectional study was conducted in Lomé, Togo, enrolling antiretroviral-treated people with HIV aged from 18 months to 24 years. Plasma HIV-1 viral load and antiretroviral concentrations were measured. Next-Generation Sequencing (NGS) of protease, Reverse Transcriptase (RT) and integrase was performed on all samples with viral load >200 c/mL. Drug resistance mutations (DRMs) were identified and interpreted using the ANRS-MIE algorithm.
Results: 264 participants were enrolled (median age=17 years), 226 received a DTG-based regimen for a median of 20.5 months. Among them, virological suppression at the 200 c/mL threshold in 80.0% of the participants. Plasma DTG concentrations were adequate (i.e., >640 ng/mL), suboptimal and below the limit of quantification in 74.1%, 6.7% and 19.2% of participants receiving DTG, respectively. Overall, viruses resistant to any of Nucleoside RT Inhibitors, Non-NRTIs, and protease inhibitors were found in 52%, 66% and 1.6% of participants, respectively. A major integrase inhibitor DRM was observed in 9.4% (n=3/32, R263K, E138A-G140A-Q148R, and N155H) of participants with a viral load >200 c/mL.
Conclusions: These first findings in such a large series of adolescents in a low-income country, showed a good virological response of 80% and the presence of an integrase DRM in 9.4% of the virological failures, supporting the need to monitor DTG drug resistance to reduce the risk of resistance acquisition.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)