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HIV DNA Sequencing to Detect Archived Antiretroviral Drug Resistance.
Geretti, Anna Maria; Blanco, Jose Luis; Marcelin, Anne Genevieve; Perno, Carlo Federico; Stellbrink, Hans Jurgen; Turner, Dan; Zengin, Tuba.
Afiliación
  • Geretti AM; Department of Infectious Diseases, Fondazione PTV and University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy. anna_maria.geretti@kcl.ac.uk.
  • Blanco JL; School of Immunology & Microbial Sciences, King's College London, London, UK. anna_maria.geretti@kcl.ac.uk.
  • Marcelin AG; Infectious Diseases Department, Hospital Clinic of Barcelona, Barcelona, Spain.
  • Perno CF; Infectious Diseases & AIDS Unit Hospital Clinic Barcelona, University of Barcelona, Barcelona, Spain.
  • Stellbrink HJ; Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié-Salpêtrière, Virologie, 75013, Paris, France.
  • Turner D; Multimodal Medicine Research Area, Children Hospital IRCCS Bambino Gesù, Rome, Italy.
  • Zengin T; ICH Infectious Diseases Center, Hamburg, Germany.
Infect Dis Ther ; 11(5): 1793-1803, 2022 Oct.
Article en En | MEDLINE | ID: mdl-35915392
INTRODUCTION: Proviral HIV DNA integrated within CD4 T-cells maintains an archive of viral variants that replicate during the course of the infection, including variants with reduced drug susceptibility. We considered studies that investigated archived drug resistance, with a focus on virologically suppressed patients and highlighted interpretative caveats and gaps in knowledge. RESULTS: Either Sanger or deep sequencing can be used to investigate resistance-associated mutations (RAMs) in HIV DNA recovered from peripheral blood. Neither technique is free of limitations. Furthermore, evidence regarding the establishment, maintenance, expression and clinical significance of archived drug-resistant variants is conflicting. This in part reflects the complexity of the HIV proviral landscape and its dynamics during therapy. Clinically, detection of RAMs in cellular HIV DNA has a variable impact on treatment outcomes, modulated by the drugs affected, treatment duration and additional determinants of virological failure, including those leading to suboptimal drug exposure. CONCLUSIONS: Sequencing cellular HIV DNA can provide helpful complementary information in treatment-experienced patients with suppressed plasma HIV RNA who require a change of regimen. However, care should be taken when interpreting the results. Presence of RAMs is not necessarily a barrier to treatment success. Conversely, even the most sensitive sequencing techniques will fail to provide a comprehensive view of the HIV DNA archive. To inform treatment decisions appropriately, the overall clinical and treatment history of a patient must always be considered alongside the results of resistance testing. Prospective controlled studies are needed to validate the utility of drug resistance testing using cellular HIV DNA.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Infect Dis Ther Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Nueva Zelanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Infect Dis Ther Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Nueva Zelanda