Autor: |
Giammarino, Federica, Salazar, Adolfo de, Malet, Isabelle, Viñuela, Laura, Fuentes, Ana, Saladini, Francesco, Bartolini, Niccolò, Charpentier, Charlotte, Lambert-Niclot, Sidonie, Sterrantino, Gaetana, Colao, Maria Grazia, Micheli, Valeria, Bertoli, Ada, Fabeni, Lavinia, Teyssou, Elisa, Delgado, Rafael, Falces-Romero, Iker, Aguilera, Antonio, Gomes, Perpetua, Paraskevis, Dimitrios |
Předmět: |
|
Zdroj: |
Journal of Infectious Diseases; 6/15/2024, Vol. 229 Issue 6, p1796-1802, 7p |
Abstrakt: |
Background Limited data are available regarding the susceptibility of the reverse transcriptase V106 polymorphism to doravirine. Methods 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. Results 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. Conclusions 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. Clinical Trials Registration NCT04894357. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
|