Tenofovir is effective alone or with emtricitabine in adefovir-treated patients with chronic-hepatitis B virus infection.
OBJECTIVE
We compared treatments for patients with chronic hepatitis B virus (HBV) infection who had an incomplete response to adefovir dipivoxil (ADV). We evaluated a combination of fixed-dose emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) from the start (early combination) versus TDF as monotherapy.


METHODS
Patients (n = 105) were randomly assigned to groups given TDF (n = 53) or FTC/TDF (n = 52). End points included HBV DNA suppression, biochemical and serologic response, and response by baseline or developed resistance mutations through 48 weeks of treatment. Patients given TDF monotherapy had the option to receive FTC, as fixed-dose FTC/TDF, if viremia persisted after week 24.


RESULTS
At baseline, patients' mean HBV DNA level was 5.97 log(10) copies/mL, and 58% had received lamivudine (LAM); LAM- and ADV-associated mutations were detected in 13 and 10 patients, respectively, by population sequencing and in 14 and 18 patients, respectively, by reverse hybridization line probe assay (INNO-LiPA HBV DR). Through week 24 (direct comparison of blinded therapy), viral decay curves were identical between groups. At week 48, 81% of patients initially given TDF or TDF/FTC had HBV DNA levels below 400 copies/mL. The presence of baseline LAM- or ADV-associated mutations did not affect response. Adherence to therapy appeared to be the primary factor associated with HBV DNA levels below 400 copies/mL at week 48.


CONCLUSIONS
TDF monotherapy and the combination of FTC and TDF had similar efficacy in patients with incomplete viral suppression after therapy with ADV; response was not influenced by the presence of baseline LAM- or ADV-associated mutations. Initial monotherapy followed by combination therapy was as effective as early combination therapy.
Berg
Thomas
T
Universitätsklinik Leipzig, Leipzig, Germany.
Marcellin
Patrick
P
Zoulim
Fabien
F
Moller
Bernd
B
Trinh
Huy
H
Chan
Sing
S
Suarez
Emilio
E
Lavocat
Fabien
F
Snow-Lampart
Andrea
A
Frederick
David
D
Sorbel
Jeff
J
Borroto-Esoda
Katyna
K
Oldach
David
D
Rousseau
Franck
F
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000410:Alanine Transaminase; D000068679:Emtricitabine; D000225:Adenine; C106812:adefovir dipivoxil