Complex dynamics of hepatitis B virus resistance to adefovir
| العنوان: | Complex dynamics of hepatitis B virus resistance to adefovir |
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| المؤلفون: | Coralie Pallier, Rozenn Brillet, Jean-Michel Pawlotsky, Christophe Hézode, Christophe Rodriguez, Patrice Nordmann |
| المساهمون: | Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de bactériologie et virologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Guellaen, Georges |
| المصدر: | Hepatology Hepatology, Wiley-Blackwell, 2009, 49 (1), pp.50-9. ⟨10.1002/hep.22634⟩ |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Adult, Male, Hepatitis B virus, Molecular Sequence Data, Population, Organophosphonates, Virus Replication, medicine.disease_cause, Antiviral Agents, Article, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Orthohepadnavirus, Drug Resistance, Viral, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Adefovir, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, 030304 developmental biology, 0303 health sciences, education.field_of_study, Hepatology, Reverse-transcriptase inhibitor, biology, Reverse Transcriptase Polymerase Chain Reaction, Adenine, virus diseases, Lamivudine, Middle Aged, Hepatitis B, medicine.disease, biology.organism_classification, Virology, digestive system diseases, 3. Good health, Hepadnaviridae, DNA, Viral, Female, 030211 gastroenterology & hepatology, medicine.drug |
| الوصف: | In patients with hepatitis B e antigen-negative chronic hepatitis B, adefovir dipivoxil administration selects variants bearing reverse transcriptase rtN236T and/or rtA181V/T substitutions in 29% of cases after 5 years. The aim of this study was to characterize the dynamics of adefovir-resistant variant populations during adefovir monotherapy in order to better understand the molecular mechanisms underlying hepatitis B virus resistance to this class of nucleotide analogues. Patients included in a 240-week clinical trial of adefovir monotherapy who developed adefovir resistance-associated substitutions were studied. The dynamics of hepatitis B virus populations were analyzed over time, after generating nearly 4,000 full-length reverse transcriptase sequences, and compared with the replication kinetics of the virus during therapy. Whatever the viral kinetics pattern, adefovir resistance was characterized by exclusive detection of a dominant wild-type, adefovir-sensitive variant population at baseline and late and gradual selection by adefovir of several coexisting resistant viral populations, defined by the presence of amino acid substitutions at position rt236, position rt181, or both. The gain in fitness of one or the other of these resistant populations during adefovir administration was never associated with the selection of additional amino acid substitutions in the reverse transcriptase. Conclusion: Our results suggest that adefovir administration selects poorly fit preexisting or emerging viral populations with low-level adefovir resistance, which subsequently compete to fill the replication space. Viral kinetics depends on the initial virological response to adefovir. Lamivudine add-on restores some antiviral efficacy, but adefovir-resistant variants remain predominant. Whether these adefovir resistance–associated substitutions may confer cross-resistance to tenofovir in vivo will need to be determined. (HEPATOLOGY 2009;49:50-59.) |
| وصف الملف: | application/pdf |
| تدمد: | 0270-9139 1527-3350 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd01ff7e2393192685e9174d0fbfa401Test https://doi.org/10.1002/hep.22634Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fd01ff7e2393192685e9174d0fbfa401 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 02709139 15273350 |
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