2. Academic Validation
  3. Prevalence and phenotypic susceptibility to doravirine of the HIV-1 reverse transcriptase V106I polymorphism in B and non-B subtypes

Prevalence and phenotypic susceptibility to doravirine of the HIV-1 reverse transcriptase V106I polymorphism in B and non-B subtypes

  • J Infect Dis. 2024 Jan 11:jiae010. doi: 10.1093/infdis/jiae010.
Federica Giammarino 1,  Adolfo de Salazar 2 3 4,  Isabelle Malet 5,  Laura Viñuela 2 3 4,  Ana Fuentes 2 3 4,  Francesco Saladini 1,  Niccolò Bartolini 1,  Charlotte Charpentier 6,  Sidonie Lambert-Niclot 7,  Gaetana Sterrantino 8,  Maria Grazia Colao 9,  Valeria Micheli 10,  Ada Bertoli 11 12,  Lavinia Fabeni 13,  Elisa Teyssou 5,  Rafael Delgado 14,  Iker Falces-Romero 4 15,  Antonio Aguilera 16,  Perpetua Gomes 17 18,  Dimitrios Paraskevis 19,  Maria M Santoro 12,  Francesca Ceccherini-Silberstein 12,  Anne-Genevieve Marcelin 5,  Cristina Moreno 4 20,  Maurizio Zazzi 1,  Federico García 2 3 4
Affiliations

Affiliations

  • 1 University of Siena, Department of Medical Biotechnologies, Siena, Italy.
  • 2 Hospital Universitario Clinico San Cecilio, Clinical Microbiology, Granada, Spain.
  • 3 Instituto de Investigación Biosanitaria, IBS.GRANADA.
  • 4 CIBER de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
  • 5 Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, Paris, France.
  • 6 Service de Virologie, Université Paris Cité, INSERM, IAME, UMR 1137, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.
  • 7 Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Saint-Antoine, Laboratoire de Virologie, Paris, France.
  • 8 University of Florence, Department of Clinical and Experimental Medicine, Florence, Italy.
  • 9 Careggi Hospital, Laboratory of Microbiology and Virology, Florence, Italy.
  • 10 Sacco University Hospital, Department of Clinical Microbiology, Virology and Bioemergencies, Milan, Italy.
  • 11 University Hospital "Tor Vergata", Laboratory of Virology, Rome, Italy.
  • 12 University of Rome "Tor Vergata", Department of Experimental Medicine, Rome, Italy.
  • 13 "Lazzaro Spallanzani"-IRCCS, National Institute for Infectious Diseases, Virology and Biosafety Laboratories Unit, Rome, Italy.
  • 14 Hospital 12 de Octubre, Clinical Microbiology Service, Madrid, Spain. Instituto de Investigación Hospital 12 de Octubre (Imas12), Madrid, Spain.
  • 15 Hospital La Paz, Clinical Microbiology Service, Madrid, Spain.
  • 16 Hospital Clínico Universitario de Santiago, Clinical Microbiology Service, IDIS, Santiago de Compostela, Spain.
  • 17 Egas Moniz Center for Interdisciplinary Research (CiiEM). Egas Moniz School of Health & Science, 2829-511 Caparica, Almada, Portugal.
  • 18 Centro Hospitalar Lisboa Ocidental - HEM, Laboratório de Biología Molecular, LMCBM, SPC, Lisboa, Portugal.
  • 19 National and Kapodistrian University of Athens, Department of Hygiene, Epidemiology and Medical Statistics, Athens, Greece.
  • 20 National Centre for Epidemiology, Institute of Health Carlos III, Madrid, Spain.
PMID: 38206187 DOI: 10.1093/infdis/jiae010
Abstract

Aim: To evaluate the prevalence and in vitro susceptibility to doravirine of RT-V106I polymorphism detected in samples collected from drug-naïve subjects.

Methods: Doravirine susceptibility was measured in site-directed mutants (SDMs) containing V106I, V106A, V106 M 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 PLWH.

Results: HIV-1 B subtype was detected in 1523/2705 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, V106 M, and Y188L. Clinically-derived viruses tested included 22 B (median FC 1.2 [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.

Keywords

Doravirine; HIV; Resistance; V106I.

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