Effects of high-dose oral acyclovir on herpesvirus disease and survival in patients with advanced HIV disease: a double-blind, placebo-controlled study. European-Australian Acyclovir Study Group.

OBJECTIVE

To determine the efficacy of high-dose oral acyclovir in preventing cytomegalovirus (CMV) and other herpesvirus disease in patients with advanced HIV disease and to evaluate its effect on patient survival.

DESIGN

Double-blind, placebo-controlled randomized trial of up to 1 year's therapy.

SETTING

Outpatient clinics in 16 hospitals in Europe and Australia.

PARTICIPANTS

A total of 302 patients with Centers for Disease Control and Prevention stage IV HIV disease, seropositive for CMV and with CD4+ lymphocyte counts < or = 150 x 10(6)/l.

INTERVENTIONS

Oral acyclovir (800 mg, four times daily) or matching placebo for 48 weeks.

MAIN OUTCOME MEASURES

Time to development of CMV and other herpesvirus disease. Following the results of another study, the protocol was amended to make survival a second major endpoint.

RESULTS

Acyclovir failed to reduce the incidence of CMV disease: the probability of developing CMV disease at 1 year was 0.24 and 0.23 in the placebo and acyclovir groups, respectively (P = 0.53). However, acyclovir significantly reduced the probability of dying at 1 year of follow-up (from 0.39 to 0.23; P = 0.018). As expected, acyclovir significantly reduced the incidence and frequency of herpes simplex virus disease. There were no notable differences between treatment groups in clinically adverse experiences and no changes in haematological parameters to indicate clinically significant drug-induced toxicity.

CONCLUSIONS

High-dose acyclovir failed to reduce the incidence of CMV disease, but significantly reduced the probability of dying at 1 year of follow-up.