Prevalence and Phenotypic Susceptibility to Doravirine of the HIV-1 Reverse Transcriptase V106I Polymorphism in B and Non-B Subtypes
Year: 2024
Type: article
Abstract: 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.
Authors: 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
Institutions: University of Siena, Instituto de Salud Carlos III, Instituto de Investigación Biosanitaria de Granada, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red Enfermedades Infecciosas, Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Institut Pierre Louis d‘Épidémiologie et de Santé Publique, Université Paris Cité, Hôpital Bichat-Claude-Bernard, Infection, Anti-microbiens, Modélisation, Evolution, Hôpital Saint-Antoine, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Luigi Sacco Hospital, University of Rome Tor Vergata, Policlinico Tor Vergata, Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani, Istituti di Ricovero e Cura a Carattere Scientifico, Research Institute Hospital 12 de Octubre, Hospital Universitario 12 De Octubre, Hospital Universitario La Paz, Instituto de Investigación Sanitaria de Santiago, Escola Superior de Saúde Egas Moniz, Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Centro de Investigação Interdisciplinar Egas Moniz, National and Kapodistrian University of Athens
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Instituto de Salud Carlos III
Awards: G6452109243, G792176526
OpenAlex ID: W4390739710