Version 1
: Received: 28 August 2024 / Approved: 29 August 2024 / Online: 30 August 2024 (10:48:30 CEST)
How to cite:
Reddy, N.; Papathanasopoulos, M.; Steegen, K.; Basson, A. E. K103N, V106M and Y188L Significantly Reduce HIV-1 Subtype C Phenotypic Susceptibility to Doravirine. Preprints2024, 2024082163. https://doi.org/10.20944/preprints202408.2163.v1
Reddy, N.; Papathanasopoulos, M.; Steegen, K.; Basson, A. E. K103N, V106M and Y188L Significantly Reduce HIV-1 Subtype C Phenotypic Susceptibility to Doravirine. Preprints 2024, 2024082163. https://doi.org/10.20944/preprints202408.2163.v1
Reddy, N.; Papathanasopoulos, M.; Steegen, K.; Basson, A. E. K103N, V106M and Y188L Significantly Reduce HIV-1 Subtype C Phenotypic Susceptibility to Doravirine. Preprints2024, 2024082163. https://doi.org/10.20944/preprints202408.2163.v1
APA Style
Reddy, N., Papathanasopoulos, M., Steegen, K., & Basson, A. E. (2024). K103N, V106M and Y188L Significantly Reduce HIV-1 Subtype C Phenotypic Susceptibility to Doravirine. Preprints. https://doi.org/10.20944/preprints202408.2163.v1
Chicago/Turabian Style
Reddy, N., Kim Steegen and Adriaan Erasmus Basson. 2024 "K103N, V106M and Y188L Significantly Reduce HIV-1 Subtype C Phenotypic Susceptibility to Doravirine" Preprints. https://doi.org/10.20944/preprints202408.2163.v1
Abstract
Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with efficacy against some NNRTI resistant mutants. Although DOR resistance mutations are established for HIV-1 subtype B, it is less clear for non-B subtypes. This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others didn’t significantly impact DOR susceptibility. We observed agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y188L caused high-level resistance, in agreement with the predictions. These mutations are frequently observed in patients failing efavirenz or nevirapine-based first-line regimens. However, they are also observed in those failing a protease inhibitor-based second-line regimen, as we have observed in our database. Genotypic drug resistance testing is therefore vital prior to initiation on DOR-based treatment for those previously exposed to efavirenz or nevirapine.
Keywords
HIV; NNRTI; doravirine; phenotypic; resistance; subtype C
Subject
Medicine and Pharmacology, Tropical Medicine
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
