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A MULTICENTER ANALYSIS OF ANTIVIRAL
RESPONSE AFTER ONE YEAR OF TENOFOVIR MONO-THERAPY IN HBV MONO-INFECTED PATIENTS WITH PRIOR NUCLEOS(T)IDE ANALOGUE EXPERIENCE
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Reported by Jules Levin
EASL
APRIL 2008, Milan, Italy
F. van Bommel1; R. A. De Man2; J. Petersen6; A. Erhardt3; D. Huppe4;
K. Stein5; P. Buggisch6; W. Bocher7; C. Sarrazin8, 9; J. Trojan9;
U. Spengler10; J. G. Reijnders2; B. Moller11; H. E. Wasmuth12; P. Rohde13;
H. Feucht14; B. Wiedenmann1; T. Berg1
1. Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charite-Universitatsmedizin Berlin, Germany. 2. Department of Gastroenterology
and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 3. Klinik fur Gastroenterologie, Hepatologie und
Infektiologie, Universitatsklinikum Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Germany. 4. Gastroenterologische Gemeinschaftspraxis,
Herne, Germany. 5. Innere Medizin IV, Universitatsklinikum Heidelberg, Heidelberg, Germany. 6. I. Medizinische Klinik, Universitatsklinikum
Hamburg-Eppendorf, Hamburg, Germany. 7. I. Medizinische Klinik und Poliklinik, Johannes Gutenberg Universitat Mainz, Mainz, Germany. 8. Klinik
fur Innere Medizin II, Universitatsklinikum des Saarlandes, Homburg an der Saar, Germany. 9. Medizinische Klinik I, Johan Wolfgang Goethe
Universitat, Frankfurt am Main, Germany. 10. Zentrum fur Innere Medizin, Universitatsklinikum Bonn, Oklahoma, OK, USA. 11. Hepatologische
Schwerpunktpraxis, Berlin, Germany. 12. Medizinische Klinik III, Universitatsklinikum Aachen, Germany. 13. Abteilung fur Gastroenterologie, St.
Marien Hospital, Hamm, Germany. 14. Institut fur Medizinische Mikrobiologie und Immunologie, Universitats-Krankenhaus Eppendorf, Hamburg,
Germany.
AUTHOR SUMMARY
Treatment with TDF in this cohort of treatment-experienced patients resulted in potent suppression of HBV DNA
Treatment response to TDF was independent of HBV genotype, YMDD mutations or HBe-Ag status at baseline TDF
Patients with genotypic resistance to ADV at baseline had a lower probability of achieving HBV DNA suppression during TDF treatment.
Virologic breakthrough was not observed during the follow-up, independent of presence of genotypic ADV resistance at baseline TDF
Favorable safety and tolerability profile was observed with TDF
Aim of The Study
Evaluation of long-term efficacy and safety of tenofovir disoproxil fumarate (TDF) monotherapy in treatment-experienced patients with HBV monoinfection
Frequency of viral breakthrough due to HBV resistance
STUDY DESIGN
· Retrospective Cohort Analysis of the follow up of treatment with TDF 300 mg QD monotherapy in HBV-monoinfected patients
· 16 centers participated in Germany and The Netherlands
· A limitation of retrospective studies is the potential for selection bias
- Therefore, data from all patients with HBV monoinfection and TDF
treatment were collected
· Frozen serum samples from baseline were obtained if available
ENDPOINTS
Primary Endpoint:
HBV DNA levels <400 copies/mL, (69 IU/mL, Cobas Amplicor assay, Roche)
Secondary Endpoints:
· HBeAg and HBsAg loss/seroconversion
· Normal ALT
· Resistance development
· Safety and tolerability
METHODS
· Inclusion criteria
- chronic HBV monoinfection
- history of treatment with nucleos(t)ide analogues
- baseline HBV DNA > 104 copies/ml at start of TDF treatment
- treatment with TDF > 6 months
· All patients had given informed consent for treatment with TDF
· Clinical and laboratory data (HBV DNA levels, ALT, creatinine) collected prospectively were retrospectively analyzed from TDF baseline and every 3-6 months during TDF treatment
· Screening for HBV resistance mutations at baseline TDF from frozen serum samples (direct sequencing)
Results: Patients
168 patients with chronic HBV monoinfection who initiated TDF therapy between 2002 and 2007 at the 16 participating centers
37 patients were excluded due to:
- HBV DNA < 104 copies/mL at TDF baseline (n=9)
- treatment with TDF < 6 months (n=14)
- treatment naive (n=6)
- non-compliance to TDF as reported by treating physician (n=8)
· 131 patients in analysis population (median time of on treatment observation 23 [6-57] months)
· 21 of 131 patients had genotypic resistance to adefovir
Safety and Tolerability
· During the follow-up period (median 20 months), no clinically significant side effects related to TDF were reported
· One patient showed temporary mild creatinine elevation at month 12; creatinine levels remained within normal range in all other patients
· No virologic breakthrough (increase of HBV DNA > 1 log10 copies/mL from nadir) observed
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