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Prevalence and Phenotypic Susceptibility to Doravirine of the HIV-1 Reverse Transcriptase V106I Polymorphism in B and Non-B Subtypes.
Giammarino, Federica; de Salazar, Adolfo; 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; Santoro, Maria M; Ceccherini-Silberstein, Francesca; Marcelin, Anne-Genevieve; Moreno, Cristina; Zazzi, Maurizio; García, Federico.
Afiliación
  • Giammarino F; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • de Salazar A; Clinical Microbiology, Hospital Universitario Clinico San Cecilio, Granada, Spain.
  • Malet I; Instituto de Investigación Biosanitaria (ibs.Granada), Granada, Spain.
  • Viñuela L; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
  • Fuentes A; Laboratoire de Virologie, Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.
  • Saladini F; Clinical Microbiology, Hospital Universitario Clinico San Cecilio, Granada, Spain.
  • Bartolini N; Instituto de Investigación Biosanitaria (ibs.Granada), Granada, Spain.
  • Charpentier C; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
  • Lambert-Niclot S; Clinical Microbiology, Hospital Universitario Clinico San Cecilio, Granada, Spain.
  • Sterrantino G; Instituto de Investigación Biosanitaria (ibs.Granada), Granada, Spain.
  • Colao MG; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
  • Micheli V; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Bertoli A; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Fabeni L; Service de Virologie, Université Paris Cité, INSERM, IAME, UMR 1137, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Paris, France.
  • Teyssou E; Laboratoire de Virologie, Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France.
  • Delgado R; Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.
  • Falces-Romero I; Laboratory of Microbiology and Virology, Careggi Hospital, Florence, Italy.
  • Aguilera A; Department of Clinical Microbiology, Virology, and Bioemergencies, Sacco University Hospital, Milan, Italy.
  • Gomes P; Laboratory of Virology, University Hospital Tor Vergata, Rome, Italy.
  • Paraskevis D; Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
  • Santoro MM; Virology and Biosafety Laboratories Unit, Lazzaro Spallanzani-IRCCS, National Institute for Infectious Diseases, Rome, Italy.
  • Ceccherini-Silberstein F; Laboratoire de Virologie, Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.
  • Marcelin AG; Clinical Microbiology Service, Instituto de Investigación, Hospital 12 de Octubre, Madrid, Spain.
  • Moreno C; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
  • Zazzi M; Clinical Microbiology Service, Hospital La Paz, Madrid, Spain.
  • García F; Clinical Microbiology Service, Hospital Clínico Universitario de Santiago, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.
J Infect Dis ; 229(6): 1796-1802, 2024 Jun 14.
Article en En | MEDLINE | ID: mdl-38206187
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piridonas / Triazoles / Infecciones por VIH / VIH-1 / Fármacos Anti-VIH / Farmacorresistencia Viral / Transcriptasa Inversa del VIH Tipo de estudio: Prevalence_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Infect Dis Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piridonas / Triazoles / Infecciones por VIH / VIH-1 / Fármacos Anti-VIH / Farmacorresistencia Viral / Transcriptasa Inversa del VIH Tipo de estudio: Prevalence_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Infect Dis Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos