A pilot study of 2',3'-dideoxyinosine for the treatment of chronic hepatitis B.
The nucleoside analog 2',3'-dideoxyinosine, currently being used to treat patients infected with the human immunodeficiency virus, has been shown to inhibit viral replication in certain cell culture systems of hepatitis B virus and the duck model of chronic hepatitis B infection. We studied the effect of dideoxyinosine on viral replication in patients with chronic hepatitis B. In the initial dose-finding phase, patients received sequential 2-wk courses of dideoxyinosine in escalating doses of 3, 6 and 9 mg/kg/day. In the second, long-term treatment phase, patients received dideoxyinosine at a dose of 9 mg/kg/day for 12 wk. Dideoxyinosine was given orally in three divided doses. The effects of dideoxyinosine on hepatitis B were assessed by serial measurements of ALT, hepatitis B virus DNA and DNA polymerase activity in serum. Six patients completed the dose-finding phase, and five patients continued into the long-term treatment phase. No significant differences were seen in serum aminotransferases, hepatitis B virus DNA levels or DNA polymerase activity at any time during treatment when compared with pretreatment levels. All patients remained positive for HBeAg during treatment and during 6 mo of follow-up. Thus at the doses tested, dideoxyinosine had no appreciable effect on viral replication in patients with chronic hepatitis B.
Fried
M W
MW
Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Korenman
J C
JC
Di Bisceglie
A M
AM
Park
Y
Y
Waggoner
J G
JG
Mitsuya
H
H
Hartman
N R
NR
Yarchoan
R
R
Broder
S
S
Hoofnagle
J H
JH
D000328:Adult; D002908:Chronic Disease; D004279:DNA, Viral / Q000097:blood; D004259:DNA-Directed DNA Polymerase / Q000097:blood; D016049:Didanosine / Q000627:therapeutic use*; D006509:Hepatitis B / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D008297:Male; D010865:Pilot Projects
D004279:DNA, Viral; D004259:DNA-Directed DNA Polymerase; D016049:Didanosine