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 from patients with primary biliary cirrhosis (PBC). Uncontrolled studies using combination anti-retroviral therapy have reported significant biochemical and histological improvement. Aim: 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.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 anti-viral vs. placebo arms with improvements in serial alkaline phosphatase (P < 0.04), alanine aminotransferase (P < 0.03) and aspartate aminotransferase (P < 0.04) levels as well as clinical score (P < 0.02). After 6 months, 25% of patients in the placebo arm and 4% in the anti-viral 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 anti-viral therapy in PBC patients with human betaretrovirus infection.