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- Title
Evaluation of HIV-1 capsid genetic variability and lenacapavir (GS-6207) drug resistance-associated mutations according to viral clades among drug-naive individuals.
- Authors
Nka, Alex Durand; Bouba, Yagai; Teto, Georges; Semengue, Ezéchiel Ngoufack Jagni; Takou, Désiré Komego; Ngueko, Aurelie Minelle Kengni; Fabeni, Lavinia; Carioti, Luca; Armenia, Daniele; Pabo, Willy; Dambaya, Béatrice; Sosso, Samuel Martin; Colizzi, Vittorio; Perno, Carlo-Federico; Ceccherini-Silberstein, Francesca; Santoro, Maria Mercedes; Fokam, Joseph; Ndjolo, Alexis
- Abstract
<bold>Objectives: </bold>We evaluated the HIV-1 capsid genetic variability and lenacapavir drug resistance-associated mutations (DRMs) among drug-naive individuals across HIV-1 clades.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
GENETIC variation; VIRAL mutation; HIV; CAPSIDS; AMINO acids; VIRAL replication; ANTIVIRAL agents
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2023, Vol 78, Issue 1, p272
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkac388