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Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern
OBJECTIVE: To investigate the prevalence and determinants of virologic failure and acquired drug resistance-associated mutations (DRMs) in HIV-infected children and adolescents in rural Tanzania. DESIGN: Prospective cohort study with cross-sectional analysis. METHODS: All children 18 years or less a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131685/ https://www.ncbi.nlm.nih.gov/pubmed/27677163 http://dx.doi.org/10.1097/QAD.0000000000001273 |
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author | Muri, Lukas Gamell, Anna Ntamatungiro, Alex J. Glass, Tracy R. Luwanda, Lameck B. Battegay, Manuel Furrer, Hansjakob Hatz, Christoph Tanner, Marcel Felger, Ingrid Klimkait, Thomas Letang, Emilio |
author_facet | Muri, Lukas Gamell, Anna Ntamatungiro, Alex J. Glass, Tracy R. Luwanda, Lameck B. Battegay, Manuel Furrer, Hansjakob Hatz, Christoph Tanner, Marcel Felger, Ingrid Klimkait, Thomas Letang, Emilio |
author_sort | Muri, Lukas |
collection | PubMed |
description | OBJECTIVE: To investigate the prevalence and determinants of virologic failure and acquired drug resistance-associated mutations (DRMs) in HIV-infected children and adolescents in rural Tanzania. DESIGN: Prospective cohort study with cross-sectional analysis. METHODS: All children 18 years or less attending the paediatric HIV Clinic of Ifakara and on antiretroviral therapy (ART) for at least 12 months were enrolled. Participants with virologic failure were tested for HIV-DRM. Pre-ART samples were used to discriminate acquired and transmitted resistances. Multivariate logistic regression analysis identified factors associated with virologic failure and the acquisition of HIV-DRM. RESULTS: Among 213 children on ART for a median of 4.3 years, 25.4% failed virologically. ART-associated DRM were identified in 90%, with multiclass resistances in 79%. Pre-ART data suggested that more than 85% had acquired key mutations during treatment. Suboptimal adherence [odds ratio (OR) = 3.90; 95% confidence interval (CI) 1.11–13.68], female sex (aOR = 2.57; 95% CI 1.03–6.45), and current nonnucleoside reverse transcriptase inhibitor-based ART (aOR = 7.32; 95% CI 1.51–35.46 compared with protease inhibitor-based) independently increased the odds of virologic failure. CD4(+) T-cell percentage (aOR = 0.20; 0.10–0.40 per additional 10%) and older age at ART initiation (aOR = 0.84 per additional year of age; 95% CI 0.73–0.97) were protective (also in predicting acquired HIV-DRM). At the time of virologic failure, less than 5% of the children fulfilled the WHO criteria for immunologic failure. CONCLUSION: Virologic failure rates in children and adolescents were high, with the majority of ART-failing children harbouring HIV-DRM. The WHO criteria for immunologic treatment failure yielded an unacceptably low sensitivity. Viral load monitoring is urgently needed to maintain future treatment options for the millions of African children living with HIV. |
format | Online Article Text |
id | pubmed-5131685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-51316852016-12-15 Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern Muri, Lukas Gamell, Anna Ntamatungiro, Alex J. Glass, Tracy R. Luwanda, Lameck B. Battegay, Manuel Furrer, Hansjakob Hatz, Christoph Tanner, Marcel Felger, Ingrid Klimkait, Thomas Letang, Emilio AIDS Clinical Science OBJECTIVE: To investigate the prevalence and determinants of virologic failure and acquired drug resistance-associated mutations (DRMs) in HIV-infected children and adolescents in rural Tanzania. DESIGN: Prospective cohort study with cross-sectional analysis. METHODS: All children 18 years or less attending the paediatric HIV Clinic of Ifakara and on antiretroviral therapy (ART) for at least 12 months were enrolled. Participants with virologic failure were tested for HIV-DRM. Pre-ART samples were used to discriminate acquired and transmitted resistances. Multivariate logistic regression analysis identified factors associated with virologic failure and the acquisition of HIV-DRM. RESULTS: Among 213 children on ART for a median of 4.3 years, 25.4% failed virologically. ART-associated DRM were identified in 90%, with multiclass resistances in 79%. Pre-ART data suggested that more than 85% had acquired key mutations during treatment. Suboptimal adherence [odds ratio (OR) = 3.90; 95% confidence interval (CI) 1.11–13.68], female sex (aOR = 2.57; 95% CI 1.03–6.45), and current nonnucleoside reverse transcriptase inhibitor-based ART (aOR = 7.32; 95% CI 1.51–35.46 compared with protease inhibitor-based) independently increased the odds of virologic failure. CD4(+) T-cell percentage (aOR = 0.20; 0.10–0.40 per additional 10%) and older age at ART initiation (aOR = 0.84 per additional year of age; 95% CI 0.73–0.97) were protective (also in predicting acquired HIV-DRM). At the time of virologic failure, less than 5% of the children fulfilled the WHO criteria for immunologic failure. CONCLUSION: Virologic failure rates in children and adolescents were high, with the majority of ART-failing children harbouring HIV-DRM. The WHO criteria for immunologic treatment failure yielded an unacceptably low sensitivity. Viral load monitoring is urgently needed to maintain future treatment options for the millions of African children living with HIV. Lippincott Williams & Wilkins 2017-01-02 2016-12-02 /pmc/articles/PMC5131685/ /pubmed/27677163 http://dx.doi.org/10.1097/QAD.0000000000001273 Text en Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 |
spellingShingle | Clinical Science Muri, Lukas Gamell, Anna Ntamatungiro, Alex J. Glass, Tracy R. Luwanda, Lameck B. Battegay, Manuel Furrer, Hansjakob Hatz, Christoph Tanner, Marcel Felger, Ingrid Klimkait, Thomas Letang, Emilio Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern |
title | Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern |
title_full | Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern |
title_fullStr | Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern |
title_full_unstemmed | Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern |
title_short | Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern |
title_sort | development of hiv drug resistance and therapeutic failure in children and adolescents in rural tanzania: an emerging public health concern |
topic | Clinical Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131685/ https://www.ncbi.nlm.nih.gov/pubmed/27677163 http://dx.doi.org/10.1097/QAD.0000000000001273 |
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