Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B.
OBJECTIVE
Tenofovir disoproxil fumarate (TDF), a nucleotide analogue and potent inhibitor of hepatitis B virus (HBV) polymerase, showed superior efficacy to adefovir dipivoxil in treatment of chronic hepatitis B through 48 weeks. We evaluated long-term efficacy and safety of TDF monotherapy in patients with chronic hepatitis B who were positive or negative for hepatitis B e antigen (HBeAg(+) or HBeAg(-)).


METHODS
After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, patients who underwent liver biopsy were eligible to continue the study on open-label TDF for 7 additional years; data presented were collected up to 3 years (week 144) from 85% of participants. Primary efficacy end points at week 144 included levels of HBV DNA and alanine aminotransferase, development of resistance mutations, and presence of HBeAg or hepatitis B surface antigen (HBsAg).


RESULTS
At week 144, 87% of HBeAg(-) and 72% of HBeAg(+) patients treated with TDF had levels of HBV DNA <400 copies/mL. Among patients who had previously received adefovir dipivoxil and then received TDF, 88% of the HBeAg(-) and 71% of the HBeAg(+) patients had levels of HBV DNA <400 copies/mL; overall, 81% and 74%, respectively, maintained normalized levels of alanine aminotransferase and 34% had lost HBeAg. Amino acid substitutions in HBV DNA polymerase that are associated with resistance to tenofovir were not detected in any patient. Cumulatively, 8% of HBeAg(+) patients lost HBsAg. TDF maintained a favorable safety profile for up to 3 years.


CONCLUSIONS
TDF was safe and effective in the long-term management of HBeAg(+) and HBeAg(-) patients with chronic hepatitis B.
Heathcote
E Jenny
EJ
University of Toronto, Toronto, Ontario, Canada.
Marcellin
Patrick
P
Buti
Maria
M
Gane
Edward
E
De Man
Robert A
RA
Krastev
Zahary
Z
Germanidis
George
G
Lee
Samuel S
SS
Flisiak
Robert
R
Kaita
Kelly
K
Manns
Michael
M
Kotzev
Iskren
I
Tchernev
Konstantin
K
Buggisch
Peter
P
Weilert
Frank
F
Kurdas
Oya Ovunc
OO
Shiffman
Mitchell L
ML
Trinh
Huy
H
Gurel
Selim
S
Snow-Lampart
Andrea
A
Borroto-Esoda
Katyna
K
Mondou
Elsa
E
Anderson
Jane
J
Sorbel
Jeff
J
Rousseau
Franck
F
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D004279:DNA, Viral / Q000187:drug effects; D024882:Drug Resistance, Viral / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000068698:Tenofovir; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects; D055815:Young Adult
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000068698:Tenofovir; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil