Prevalence and Phenotypic Susceptibility to Doravirine of the HIV-1 Reverse Transcriptase V106I Polymorphism in B and Non-B Subtypes

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 ParaskevisMaria M. Santoro, Francesca Ceccherini-Silberstein, Anne Genevieve Marcelin, Cristina Moreno, Maurizio Zazzi, Federico García

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)1796-1802
Number of pages7
JournalJournal of Infectious Diseases
Volume229
Issue number6
DOIs
Publication statusPublished - 15 Jun 2024

Keywords

  • doravirine
  • HIV
  • resistance
  • V106I
  • Prevalence
  • Humans
  • Middle Aged
  • Genotype
  • Male
  • Polymorphism, Genetic
  • Triazoles/pharmacology
  • Phenotype
  • Drug Resistance, Viral/genetics
  • HIV-1/genetics
  • Reverse Transcriptase Inhibitors/pharmacology
  • Adult
  • Female
  • Pyridones/pharmacology
  • HIV Infections/virology
  • HIV Reverse Transcriptase/genetics
  • Anti-HIV Agents/pharmacology

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