-
Views
-
Cite
Cite
Federica Giammarino, Adolfo de Salazar, Isabelle Malet, Laura Viñuela, Ana Fuentes, Francesco Saladini, Niccolò Bartolini, Charlotte Charpentier, Sidonie Lambert-Niclot, Gaetana Sterrantino, Maria Grazia Colao, Valeria Micheli, Ada Bertoli, Lavinia Fabeni, Elisa Teyssou, Rafael Delgado, Iker Falces-Romero, Antonio Aguilera, Perpetua Gomes, Dimitrios Paraskevis, Maria M Santoro, Francesca Ceccherini-Silberstein, Anne-Genevieve Marcelin, Cristina Moreno, Maurizio Zazzi, Federico García, Prevalence and Phenotypic Susceptibility to Doravirine of the HIV-1 Reverse Transcriptase V106I Polymorphism in B and Non-B Subtypes, The Journal of Infectious Diseases, Volume 229, Issue 6, 15 June 2024, Pages 1796–1802, https://doi.org/10.1093/infdis/jiae010
- Share Icon Share
Abstract
Limited data are available regarding the susceptibility of the reverse transcriptase V106 polymorphism to doravirine.
Doravirine susceptibility was measured in site-directed mutants (SDMs) containing V106I, V106A, V106M, and Y188L mutations in subtype B (NL4-3, HXB2) and CRF02_AG background and in recombinant viruses with RT harboring V106I alone derived from 50 people with HIV.
HIV-1 B subtype was detected in 1523 of 2705 cases. Prevalence of V106I was 3.2% in B and 2.5% in non-B subtypes, and was higher in subtype F (8.1%) and D (14.3%). Fold-changes (FC) in susceptibility for SDMs were below doravirine biological cutoff (3.0) for V106I, but not for V106A, V106M, and Y188L. Clinically derived viruses tested included 22 B (median FC, 1.2; interquartile range [IQR], 0.9–1.6) and 28 non-B subtypes (median FC, 1.8; IQR, 0.9–3.0). Nine (18%) viruses showed FC values equal or higher than the doravirine biological FC cutoff.
The prevalence of the HIV-1 RT V106I polymorphism in MeditRes HIV consortium remains low, but significantly more prevalent in subtypes D and F. V106I minimally decreased the susceptibility to doravirine in SDMs and most clinical isolates. Reduced susceptibility seems to occur at increased frequency in subtype F1; however, the clinical impact remains to be investigated.
NCT04894357.