Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection

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Abstract

As part of a combined antiretroviral regimen, doravirine is safe and effective at suppressing viral replication in both treatment-naive and treatment-experienced adults living with human immunodeficiency virus (HIV)-1 who have no history of drug resistance against doravirine. In virologically suppressed individuals switching to a combination of doravirine, lamivudine, and tenofovir disoproxil fumarate, no resistance was found after 48 weeks. In treatment-naive individuals, rare cases (<2%) of emergent drug resistance have been reported, often involving the development of substitutions at position V106. From these few clinical cases, it is inferred that crossresistance with other non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be limited. In contrast, the use of doravirine as a second NNRTI should be evaluated on a case-by-case basis in the presence of pre-existing resistance. Importantly, doravirine remains active against K103N viruses in vitro, and limited clinical evidence suggests this to be the case in patients as well. Since K103N is by far the most prevalent (<70%) NNRTI substitution found in clinical practice, resistance against doravirine-based antiretroviral therapies is expected to be rare, even for treatment-experienced individuals. This review summarizes chemical, pharmacological, and clinical information about doravirine with an emphasis on drug resistance. The efficacy results from an early phase clinical trial evaluating doravirine in combination with islatravir are also provided.

Keywords: antiretroviral therapy, doravirine, drug resistance, highly active, HIV, reverse transcriptase inhibitors.

Citation: Pham HT, Xiao MA, Principe MAV, Wong A, Mesplède T. Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Drugs in Context 2020; 9: 2019-11-4. DOI: 10.7573/dic.2019-11-4

Contributions: All authors contributed equally to the preparation of this review. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: The authors have no other relevant affiliation or financial involvement with any organization or entity with financial interests or financial conflicts with the subject discussed in the manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2020/02/dic.2019-11-4-COI.pdf

Acknowledgements: None.

Funding declaration: There was no funding associated with the preparation of this article.

Copyright: Copyright © 2020 Pham HT, Xiao MA, Principe MAV, Wong A, Mesplède T. https://doi.org/10.7573/dic.2019-11-4. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2020 Pham HT, Xiao MA, Principe MAV, Wong A, Mesplède T. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/pharmaceutical,-clinical,-and-resistance-information-on-doravirine,-a-novel-non-nucleoside-reverse-transcriptase-inhibitor-for-the-treatment-of-hiv-1-infection/

Correspondence: Thibault Mesplède, McGill AIDS Centre, Jewish General Hospital, Montréal, Québec, Canada. thibault.mesplede@mcgill.ca

Provenance: invited; externally peer reviewed.

Submitted: 18 November 2019; Peer review comments to author: 18 December 2019; Revised manuscript received: 16 January 2020; Accepted: 5 February 2020; Publication date: 3 March 2020.

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