Efficacy of tenofovir disoproxil fumarate at 240 weeks in patients with chronic hepatitis B with high baseline viral load.
We evaluated the antiviral response of patients with chronic hepatitis B (CHB) who had baseline high viral load (HVL), defined as having hepatitis B virus (HBV) DNA ≥ 9 log10 copies/mL, after 240 weeks of tenofovir disoproxil fumarate (TDF) treatment. A total of 641 hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients (129 with HVL) received 48 weeks of TDF 300 mg (HVL n = 82) or adefovir dipivoxil (ADV) 10 mg (HVL n = 47), followed by open-label TDF for an additional 192 weeks. Patients with confirmed HBV DNA ≥ 400 copies/mL on or after week 72 had the option of adding emtricitabine (FTC). By week 240, 98.3% of HVL and 99.2% of non-HVL patients on treatment achieved HBV DNA <400 copies/mL. Both groups had similar rates of histologic regression between baseline and week 240. Patients with HVL generally took longer to achieve HBV DNA <400 copies/mL than non-HVL patients, but by week 96, the percentages of patients with HBV DNA <400 copies/mL were similar in both groups. Among HVL patients, time to achieving HBV DNA <400 copies/mL was shorter among those initially receiving TDF, compared to ADV. No patient with baseline HVL had persistent viremia at week 240 or amino acid substitutions associated with TDF resistance.


CONCLUSIONS
CHB patients with HVL can achieve HBV DNA negativity with long-term TDF treatment, although time to HBV DNA <400 copies/mL may be longer, relative to patients with non-HVL.
Henry Ford Health System, Detroit, MI, USA.
Stuart C
SC
Gordon
Zahary
Z
Krastev
Andrzej
A
Horban
Jörg
J
Petersen
Jan
J
Sperl
Phillip
P
Dinh
Eduardo B
EB
Martins
Leland J
LJ
Yee
John F
JF
Flaherty
Kathryn M
KM
Kitrinos
Vinod K
VK
Rustgi
Patrick
P
Marcellin
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D010757:Phosphorous Acids / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
C574165:9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine; D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D010757:Phosphorous Acids; D003841:Deoxycytidine; D000068679:Emtricitabine; D000225:Adenine; C106812:adefovir dipivoxil