Objective: To compare the efficacy and safety of 7 days' treatment with famciclovir 500 mg twice a day versus acyclovir 400 mg five times a day, for mucocutaneous herpes simplex virus (HSV) infection in HIV-infected individuals.
Design: Randomized, double-blind, parallel-group study to demonstrate equivalence for the primary efficacy parameter.
Setting: Forty-eight hospital-based or specialist public-health clinics in 12 countries.
Patients: Two-hundred and ninety-three HIV-positive patients with recurrent HSV infection (orolabial or genital) starting treatment within 48 h of first appearance of herpetic lesions.
Main outcome measures: Proportion of patients developing new lesions during treatment (primary outcome measures); Time to complete healing of lesions, time to cessation of viral shedding, time to loss of lesion-associated symptoms, number of withdrawals due to treatment failure (secondary outcome measures).
Results: Equivalence was defined prospectively and famciclovir was equivalent to acyclovir in preventing new lesion formation: new lesions occurred in 16.7% and 13.3% of patients, respectively [difference, 3.4%; 95% confidence interval (CI), -4.8-11.5]. The groups were comparable in time to complete healing (median 7 days for both groups; hazard ratio, 1.01; 95% CI, 0.79-1.29;P = 0.95), cessation of viral shedding (median of 2 days [hazard ratio = 0.93; 95% C.I. 0.68, 1.27;p = 0.64]), and loss of lesion-associated symptoms (median 4 days; hazard ratio, 0.99; 95% CI, 0.75-1.30;P = 0.93). Similar numbers in each group withdrew because of treatment failure. There were no differences between groups in the incidence of adverse events.
Conclusions: Famciclovir given twice a day is as effective and well tolerated as high-dose acyclovir for mucocutaneous HSV infections in HIV-infected individuals, and has the convenience of less frequent dosing.