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Long‐term efficacy of tenofovir monotherapy for hepatitis B virus‐monoinfected patients after failure of nucleoside/nucleotide analogues
Author(s) -
van Bömmel Florian,
de Man Robert A.,
Wedemeyer Heiner,
Deterding Katja,
Petersen Jörg,
Buggisch Peter,
Erhardt Andreas,
Hüppe Dietrich,
Stein Kerstin,
Trojan Jörg,
Sarrazin Christoph,
Böcher Wulf O.,
Spengler Ulrich,
Wasmuth Hermann E.,
Reinders Jurrien G.P.,
Möller Bernd,
Rhode Peter,
Feucht HeinzHubert,
Wiedenmann Bertram,
Berg Thomas
Publication year - 2010
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23246
Subject(s) - tenofovir , virology , nucleoside , nucleotide , medicine , pharmacology , chemistry , human immunodeficiency virus (hiv) , biochemistry , gene
Abstract Tenofovir disoproxil fumarate (TDF) has demonstrated high antiviral efficacy in treatment‐naive patients with chronic hepatitis B virus (HBV) infection but experience in nucleoside/nucleotide analogue (NA)‐experienced patients is limited. In this retrospective multicenter study we therefore assessed the long‐term efficacy of TDF monotherapy in patients with prior failure or resistance to different NA treatments. Criteria for inclusion were HBV DNA levels >4.0 log 10 copies/mL at the start and a minimum period of TDF therapy for at least 6 months. In all, 131 patients (mean age 42 ± 12 years, 95 male, 65% hepatitis B e antigen [HBeAg]‐positive) were eligible. Pretreatment consisted of either monotherapy with lamivudine (LAM; n = 18), adefovir (ADV; n = 8), and sequential LAM‐ADV therapy (n = 73), or add‐on combination therapy with both drugs (n = 29). Three patients had failed entecavir therapy. Resistance analysis in 113 of the 131 patients revealed genotypic LAM and ADV resistance in 62% and 19% of patients, respectively. The mean HBV DNA level at TDF baseline was 7.6 ± 1.5 log 10 copies/mL. The overall cumulative proportion of patients achieving HBV DNA levels <400 copies/mL was 79% after a mean treatment duration of 23 months (range, 6–60). Although LAM resistance did not influence the antiviral efficacy of TDF, the presence of ADV resistance impaired TDF efficacy (100% versus 52% probability of HBV DNA <400 copies/mL, respectively). However, virologic breakthrough was not observed in any of the patients during the entire observation period. Loss of HBeAg occurred in 24% of patients and HBsAg loss occurred in 3%. No significant adverse events were noticed during TDF monotherapy. Conclusion: TDF monotherapy induced a potent and long‐lasting antiviral response in NA‐experienced patients with previous treatment failure. Our data may have implications for current add‐on strategies. (H EPATOLOGY 2009.)