Pharmaco-virological outcomes and genotypic resistance profiles among children and adolescents receiving a DTG-based regimen in Togo.

HIV Togo children/adolescents concentrations dolutegravir resistance

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
15 May 2024
Historique:
received: 18 12 2023
revised: 06 05 2024
accepted: 13 05 2024
medline: 15 5 2024
pubmed: 15 5 2024
entrez: 15 5 2024
Statut: aheadofprint

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

pubmed: 38748464
pii: 7674162
doi: 10.1093/cid/ciae278
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 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.

Auteurs

Yao Rodion 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.

Elom Takassi (E)

Service de pédiatrie, CHU Sylvanus Olympio, Université de Lomé, 05 BP 846 Lomé, Togo.

Gilles Peytavin (G)

Service de Pharmacologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.

Nina Dapam (N)

Espoir Vie Togo, Lomé, Togo.

Florence Damond (F)

Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.

Wone Adama Oumarou (WA)

Centre Africain de Recherche en Epidémiologie et en Santé Publique (CARESP), Lomé, Togo.

Meryem Zaidi (M)

Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.

Anna-Maria Franco-Yusti (AM)

Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.

Claver A Dagnra (CA)

Université de Lomé, Centre de Biologie Moléculaire et d'Immunologie, Lomé, Togo.

Quentin Le Hingrat (Q)

Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.

Romain Coppée (R)

Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.

Diane Descamps (D)

Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.

Fatoumata Binta Tidiane Diallo (FBT)

Togo Office, World Health Organization (WHO), Lomé, Togo.

Didier K 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.

Charlotte Charpentier (C)

Service de virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.

Classifications MeSH