Long-term efficacy of tenofovir monotherapy for hepatitis B virus-monoinfected patients after failure of nucleoside/nucleotide analogues.
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.


CONCLUSIONS
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.
van Bömmel
Florian
F
Medizinische Klinik m. S. Hepatologie und Gastroenterologie Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Germany. florian.boemmel@charite.de
de Man
Robert A
RA
Wedemeyer
Heiner
H
Deterding
Katja
K
Petersen
Jörg
J
Buggisch
Peter
P
Erhardt
Andreas
A
Hüppe
Dietrich
D
Stein
Kerstin
K
Trojan
Jörg
J
Sarrazin
Christoph
C
Böcher
Wulf O
WO
Spengler
Ulrich
U
Wasmuth
Hermann E
HE
Reinders
Jurrien G P
JG
Möller
Bernd
B
Rhode
Peter
P
Feucht
Heinz-Hubert
HH
Wiedenmann
Bertram
B
Berg
Thomas
T
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy*; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D012189:Retrospective Studies; D000068698:Tenofovir; D016896:Treatment Outcome
D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine