1. Evaluation of HIV-1 capsid genetic variability and lenacapavir (GS-6207) drug resistance-associated mutations according to viral clades among drug-naive individuals.
- Author
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Nka AD, Bouba Y, Teto G, Semengue ENJ, Takou DK, Ngueko AMK, Fabeni L, Carioti L, Armenia D, Pabo W, Dambaya B, Sosso SM, Colizzi V, Perno CF, Ceccherini-Silberstein F, Santoro MM, Fokam J, and Ndjolo A
- Subjects
- Humans, Capsid, Capsid Proteins genetics, Drug Resistance, Viral genetics, Mutation, Amino Acids genetics, Amino Acids metabolism, Amino Acids therapeutic use, Nuclear Pore Complex Proteins genetics, Nuclear Pore Complex Proteins metabolism, HIV-1 genetics, HIV Infections epidemiology, Anti-HIV Agents therapeutic use
- Abstract
Objectives: We evaluated the HIV-1 capsid genetic variability and lenacapavir drug resistance-associated mutations (DRMs) among drug-naive individuals across HIV-1 clades., Methods: A total of 2031 HIV-1 sequences from drug-naive patients were analysed for capsid amino acid modification and the prevalence of lenacapavir DRMs. Amino acid positions with <5% variability were considered as conserved and variability was analysed by HIV-1 clades., Results: Overall, 63% (148/232) of amino acid positions were conserved in the capsid protein. Of note, conservation was consistent in specific binding residues of cellular factors involved in viral replication [CypA (G89, P90), CPSF6 (Q4, N57, N74, A77, K182) and TRIM-NUP153 (R143)], while N183 (12.31%) was the only non-conserved lenacapavir binding residue. The overall prevalence (95% CI) of lenacapavir DRMs was 0.14% (0.05-0.44) (3/2031), with M66I (0.05%) and Q67H (0.05%) observed in subtype C, and T107N (0.05%) observed in CRF01_AE. Moreover, polymorphic mutations M66C (n = 85; 4.18%), Q67K (n = 78; 3.84%), K70R (n = 7; 0.34%), N74R (n = 57; 2.81%) and T107L (n = 82; 4.03%) were observed at lenacapavir resistance-associated positions., Conclusions: The low level of lenacapavir DRMs (<1%) supports its predicted effectiveness for treatment and prevention, regardless of HIV-1 clades. The established conserved regions hence serve as a hallmark for the surveillance of novel mutations potentially relevant for lenacapavir resistance., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2022
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