Six RCTs were included in the review (n=442 patients, range 8 to 146). One trial received 5 points out of 7 for quality; three trials received 4 points; one trial received 3 points; and one trial received 2 points. Only one RCT was double-blinded. Follow-up period ranged from 12 weeks to 40 weeks.
Adefovir dipivoxil plus lamivudine combination therapy groups had higher biochemical response (RR 1.18, 95% CI 1.04 to 1.35; five RCTs), virological response (RR 1.28, 95% CI 1.10 to 1.49; six RCTs), hepatitis B e antigen clearance (RR 2.09, 95% CI 1.18 to 3.72; four RCTs) and hepatitis B antigen seroconversion (RR 2.47, 95% CI 1.15 to 5.28; four RCTs) than adefovir dipivoxil monotherapy groups. The combination therapy groups also had lower rates of emergence of adefovir dipivoxil-resistant mutations than monotherapy groups (RR 0.15, 95% CI 0.03 to 0.74; four RCTs). Heterogeneity was assessed as statistically non significant in all cases.
One trial reported that combination therapy was not well tolerated in five patients with cirrhosis.
Removing the trial with the lowest quality from the analyses made the pooled estimate for biochemical response of borderline statistical significance (RR 1.19, 95% CI 1.00 to 1.42), and the differences in clearance and seroconversion non significant, but did not affect the statistical significance of the other outcomes.