@article{a091e8bfc4324f019c1420692555bc21,
title = "High levels of dual-class drug resistance in HIV-infected children failing first-line antiretroviral therapy in Southern Ethiopia",
abstract = "Clinical monitoring of pediatric HIV treatment remains a major challenge in settings where drug resistance genotyping is not routinely available. As a result, our understanding of drug resistance, and its impact on subsequent therapeutic regimens available in these settings, remains limited. We investigate the prevalence and correlates of HIV-1 drug resistance among 94 participants of the Ethiopia Pediatric HIV Cohort failing first-line combination antiretroviral therapy (cART) using dried blood spot-based genotyping. Overall, 81% (73/90) of successfully genotyped participants harbored resistance mutations, including 69% (62/90) who harbored resistance to both Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs). Strikingly, 42% of resistant participants harbored resistance to all four NRTIs recommended for second-line use in this setting, meaning that there are effectively no remaining cART options for these children. Longer cART duration and prior regimen changes were significantly associated with detection of drug resistance mutations. Replicate genotyping increased the breadth of drug resistance detected in 34% of cases, and thus is recommended for consideration when typing from blood spots. Implementation of timely drug resistance testing and access to newer antiretrovirals and drug classes are urgently needed to guide clinical decision-making and improve outcomes for HIV-infected children on first-line cART in Ethiopia.",
keywords = "Children, Dried blood spots, Drug resistance, Ethiopia, First-line combination antiretroviral therapy (cART), Genotyping, HIV, Pediatrics, Treatment failure",
author = "Tadesse, {Birkneh Tilahun} and Kinloch, {Natalie N.} and Bemuluyigza Baraki and Lapointe, {Hope R.} and Cobarrubias, {Kyle D.} and Brockman, {Mark A.} and Brumme, {Chanson J.} and Foster, {Byron A.} and Degu Jerene and Eyasu Makonnen and Eleni Aklillu and Brumme, {Zabrina L.}",
note = "Funding Information: We thank Hanwei Sudderuddin and Rachel L. Miller for technical assistance, and Jeffrey B. Joy and P. Richard Harrigan for helpful discussions. We are grateful to the participants of this study and their parents/guardians, without whom this study would not have been possible. We thank Thibault Mespl?de for the opportunity to submit this work to this special issue of Viruses. We dedicate this work to the memory of our respected colleague and mentor Mark A. Wainberg, a brilliant HIV researcher, inspiring role model and tireless advocate for treatment access and human rights. This work was supported by a Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) award (award #307-TAD, to Birkneh Tilahun Tadesse), a project grant from the Canadian Institutes for Health Research (CIHR) (PJT-148621, to Zabrina L. Brumme and Mark A. Brockman), a Mowafaghian Foundation Child Health Research Award from Simon Fraser University (SFU) Faculty of Health Sciences (to Zabrina L. Brumme), and an SFU International Engagement Fund award (to Zabrina L. Brumme, Mark A. Brockman and Birkneh Tilahun Tadesse). Natalie N. Kinloch is supported by a CIHR Frederick Banting and Charles Best Masters Scholarship. Chanson J. Brumme is supported by a CIHR Postgraduate Fellowship (MFE-146750). Mark A. Brockman holds a Tier 2 Canada Research Chair in Viral Pathogenesis and Immunity. Zabrina L. Brumme is supported by a Scholar Award from the Michael Smith Foundation for Health Research. Funding Information: We thank Hanwei Sudderuddin and Rachel L. Miller for technical assistance, and Jeffrey B. Joy and P. Richard Harrigan for helpful discussions. We are grateful to the participants of this study and their parents/guardians, without whom this study would not have been possible. We thank Thibault Mespl{\`e}de for the opportunity to submit this work to this special issue of Viruses. We dedicate this work to the memory of our respected colleague and mentor Mark A. Wainberg, a brilliant HIV researcher, inspiring role model and tireless advocate for treatment access and human rights. This work was supported by a Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) award (award #307-TAD, to Birkneh Tilahun Tadesse), a project grant from the Canadian Institutes for Health Research (CIHR) (PJT-148621, to Zabrina L. Brumme and Mark A. Brockman), a Mowafaghian Foundation Child Health Research Award from Simon Fraser University (SFU) Faculty of Health Sciences (to Zabrina L. Brumme), and an SFU International Engagement Fund award (to Zabrina L. Brumme, Mark A. Brockman and Birkneh Tilahun Tadesse). Natalie N. Kinloch is supported by a CIHR Frederick Banting and Charles Best Masters Scholarship. Chanson J. Brumme is supported by a CIHR Postgraduate Fellowship (MFE-146750). Mark A. Brockman holds a Tier 2 Canada Research Chair in Viral Pathogenesis and Immunity. Zabrina L. Brumme is supported by a Scholar Award from the Michael Smith Foundation for Health Research.",
year = "2018",
month = feb,
doi = "10.3390/v10020060",
language = "English (US)",
volume = "10",
journal = "Viruses",
issn = "1999-4915",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "2",
}