Version 1
: Received: 21 October 2024 / Approved: 21 October 2024 / Online: 22 October 2024 (09:46:48 CEST)
How to cite:
Byun, H.; Papathanasopoulos, M. A.; Steegen, K.; Basson, A. E. Thymidine Analogue Mutations with M184V Significantly Decrease Phenotypic Susceptibility of HIV-1 subtype C Reverse Transcriptase to Islatravir. Preprints2024, 2024101632. https://doi.org/10.20944/preprints202410.1632.v1
Byun, H.; Papathanasopoulos, M. A.; Steegen, K.; Basson, A. E. Thymidine Analogue Mutations with M184V Significantly Decrease Phenotypic Susceptibility of HIV-1 subtype C Reverse Transcriptase to Islatravir. Preprints 2024, 2024101632. https://doi.org/10.20944/preprints202410.1632.v1
Byun, H.; Papathanasopoulos, M. A.; Steegen, K.; Basson, A. E. Thymidine Analogue Mutations with M184V Significantly Decrease Phenotypic Susceptibility of HIV-1 subtype C Reverse Transcriptase to Islatravir. Preprints2024, 2024101632. https://doi.org/10.20944/preprints202410.1632.v1
APA Style
Byun, H., Papathanasopoulos, M. A., Steegen, K., & Basson, A. E. (2024). Thymidine Analogue Mutations with M184V Significantly Decrease Phenotypic Susceptibility of HIV-1 subtype C Reverse Transcriptase to Islatravir. Preprints. https://doi.org/10.20944/preprints202410.1632.v1
Chicago/Turabian Style
Byun, H., Kim Steegen and Adriaan Erasmus Basson. 2024 "Thymidine Analogue Mutations with M184V Significantly Decrease Phenotypic Susceptibility of HIV-1 subtype C Reverse Transcriptase to Islatravir" Preprints. https://doi.org/10.20944/preprints202410.1632.v1
Abstract
Islatravir (ISL) is the first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTtI) with novel modes of action. Data on ISL resistance is currently limited, particularly to HIV-1 non-B subtypes. This study aimed to assess prevalent nucleos(t)ide reverse transcriptase inhibitor (NRTI) resistance mutations in HIV-1 subtype C for phenotypic resistance to ISL. Prevalent single and combinations of NRTI resistance mutations were selected from a routine HIV-1 genotypic drug resistance testing database and introduced into HIV-1 subtype C-like pseudoviruses, which were then tested for ISL susceptibility. Single NRTI resistance mutations were susceptible or showed only a low level of resistance to ISL. This included thymidine analogue mutations (TAMs, i.e., M41L, D67N, K70R, T215FY, K219EQ) and non-TAMs (i.e., A62V, K65R, K70ET, L74IV, A114S, Y115F, M184V). Combinations of M184V with one or more additional NRTI resistance mutations generally displayed reduced ISL susceptibilities. This was more prominent for combinations that included M184V+TAMs, and particularly M184V+TAM-2 mutations. Combinations that included M184V+K65R did not impact significantly on ISL susceptibility. Our study suggests that ISL would be effective in treating people living with HIV (PLWH) failing tenofovir disoproxil fumarate (TDF)/lamivudine (3TC) or TDF/emtricitabine (FTC)-containing regimens but would be less effective in PLH failing zidovudine (AZT) with 3TC or FTC-containing regimens.
Keywords
HIV; antiretroviral therapy (ART); antiviral drugs; NRTI; islatravir (ISL); phenotypic; drug resistance; subtype C
Subject
Biology and Life Sciences, Virology
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.
