Hepatitis B virus genotypes and virologic response in 694 patients in phase III studies of adefovir dipivoxil1.
OBJECTIVE
Hepatitis B virus (HBV) genotype may influence disease progression and antiviral response. We therefore analyzed the frequency and distribution of genotypes in patients from 2 multinational phase III studies of adefovir dipivoxil. Antiviral efficacy of adefovir dipivoxil 10-mg therapy was examined with respect to HBV genotype, hepatitis B e antigen (HBeAg) serostatus, and race.


METHODS
HBV genotypes were assigned by phylogenetic analyses of DNA sequences amplified from baseline serum samples (n = 694).


RESULTS
Patients from Asia/Oceania were infected predominantly with genotypes B and C, whereas patients from Western European countries were infected predominantly with genotypes A and D. In Mediterranean countries, genotype D was dominant. The most common genotype in North America was C, followed by A, B, and D. Regardless of location, Asian patients were infected predominantly with genotypes B or C, whereas Caucasian patients were infected predominantly with A or D. There were significant differences in the baseline serum HBV-DNA levels of patients infected with different HBV genotypes regardless of HBeAg serostatus. Forty-eight weeks of adefovir dipivoxil 10-mg therapy resulted in potent reductions in serum HBV DNA with no significant differences based on genotype, HBeAg status, or race; similarly, there was no statistical difference in HBeAg seroconversion rates between genotypes in these patients.


CONCLUSIONS
HBV genotypes were distributed asymmetrically with respect to race, geography, and HBeAg status. Forty-eight weeks of adefovir dipivoxil therapy resulted in significant decreases in serum HBV-DNA levels in patients regardless of HBV genotype, HBeAg status, or race.
Westland
Chris
C
Gilead Sciences, Foster City, California 94404, USA.
Delaney
William
W
Yang
Huiling
H
Chen
Shan-Shan
SS
Marcellin
Patrick
P
Hadziyannis
Stephanos
S
Gish
Robert
R
Fry
John
J
Brosgart
Carol
C
Gibbs
Craig
C
Miller
Michael
M
Xiong
Shelly
S
D000225:Adenine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D001208:Asia; D004279:DNA, Viral / Q000032:analysis; D005060:Europe; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000208:ethnology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America; D063065:Organophosphonates; D010139:Pacific Islands; D010802:Phylogeny; D015995:Prevalence; D044469:Racial Groups; D012189:Retrospective Studies
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000225:Adenine; C106812:adefovir dipivoxil