Clinical trial: randomized controlled study of zidovudine and lamivudine for patients with primary biliary cirrhosis stabilized on ursodiol.
BACKGROUND
A human betaretrovirus has been characterized in patients with primary biliary cirrhosis (PBC). Uncontrolled studies using combination anti-retroviral therapy have reported significant biochemical and histological improvement.


OBJECTIVE
To conduct a double blind, randomized controlled trial as a proof of principal to link infection with PBC.


METHODS
Fifty-nine patients with an alkaline phosphatase level>1.5 upper limits of normal stabilized on ursodeoxycholic acid therapy were randomized to either 300 mg zidovudine and 150 mg lamivudine B.I.D. or placebo for 6 months.


RESULTS
None of the patients normalized alkaline phosphatase and no significant differences were observed in normalizing serum aminotransferase levels. Significant differences were observed in the antiviral versus placebo arms with improvements in serial alkaline phosphatase (p<0.04), ALT (p<0.03) and AST (p<0.04) as well as clinical score (p<0.02). After 6 months, 25% of patients in the placebo arm and 4% in the antiviral arm had evidence of virus in serum.


CONCLUSIONS
The study endpoints for normalizing hepatic biochemistry were too stringent to show efficacy for zidovudine and lamivudine therapy despite the demonstrable impact on clinical and biochemical improvement. Accordingly, more potent anti-viral regimens will be required to confirm the efficacy of antiviral therapy in PBC patients with human betaretrovirus infection.
Mason
A L
AL
Public Health Research Unit, CHUL Research Centre, Québec, Canada.
Lindor
K D
KD
Bacon
B R
BR
Vincent
C
C
Neuberger
J M
JM
Wasilenko
S T
ST
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D030121:Betaretrovirus / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012192:Retroviridae Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000188:drug therapy*; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
D000998:Antiviral Agents; D002756:Cholagogues and Choleretics; D019259:Lamivudine; D015215:Zidovudine; D014580:Ursodeoxycholic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase