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Emergent resistance to dolutegravir among INSTI-naïve patients on first-line or second-line antiretroviral therapy : a review of published cases

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Date
06/2020
Author
Cevik, Muge
Orkin, Chloe
Sax, Paul E
Keywords
Dolutegravir
HIV
Treatment failure
Treatment-naïve
Resistance
QR180 Immunology
QR355 Virology
RM Therapeutics. Pharmacology
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Abstract
None of the licensing studies of dolutegravir (DTG) reported any treatment-emergent resistance among DTG-treated individuals, though virological failure in treatment-naïve and treatment-experienced, integrase strand transfer inhibitor (INSTI)-naïve individuals has been reported in clinical practice. While the spectrum of dolutegravir-selected mutations and their effects on clinical outcome have been described, the clinical characteristics of these rare but important virological failure cases are often overlooked. In this perspective piece, we focus on key clinical aspects of emergent resistance to DTG among treatment-naïve and treatment-experienced INSTI-naïve patients, with an aim to inform clinical decision-making. Poor adherence and HIV disease factors contribute to emergent drug resistance, even in regimens with high resistance barriers. Patients with severe immunosuppression or poor adherence are under-represented in licensing studies, and these patients may be at higher risk of treatment failure with DTG resistance, which requires close clinical and laboratory follow-up.
Citation
Cevik , M , Orkin , C & Sax , P E 2020 , ' Emergent resistance to dolutegravir among INSTI-naïve patients on first-line or second-line antiretroviral therapy : a review of published cases ' , Open Forum Infectious Diseases , vol. 7 , no. 6 , ofaa202 . https://doi.org/10.1093/ofid/ofaa202
Publication
Open Forum Infectious Diseases
Status
Peer reviewed
DOI
https://doi.org/10.1093/ofid/ofaa202
ISSN
2328-8957
Type
Journal item
Rights
Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/20395

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