A RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF THE SAFETY AND EFFICACY OF ORAL GANCICLOVIR FOR PROPHYLAXIS OF CYTOMEGALOVIRUS DISEASE IN HIV-INFECTED INDIVIDUALS

Objective: Evaluate safety and efficacy of oral ganciclovir (GCV) for preventing cytomegalovirus (CMV) disease in HIV-infected persons at hi gh risk for CMV disease. Design: Double-blind, placebo-controlled, ran domized clinical trial in primary care clinics and private practice of fices specializing in the care of people with HIV. Interventions were oral GCV (1000 mg three times/day) or placebo. Protocol amendment allo wed switch to open-label oral GCV. Main outcome measures were confirme d CMV retinal or gastrointestinal mucosal disease, and death. The stud y enrolled 994 people co-infected with CMV and HIV, with at least one CD4 count recorded < 100 x 10(6) cells/l. Results: At study completion (15 months median follow-up), CMV event rates in the oral GCV and con trol groups were 13.1 and 14.6 per 100 person years, respectively, a h azard ratio (HR) of 0.92 [95% confidence interval (CI), 0.65-1.27; P = 0.6]. At protocol amendment event rates were 12.7 and 15.0, respectiv ely (HR, 0.85; 95% CI, 0.56-1.30; P = 0.45). At study completion, even t rates for death were 26.6 and 32.0 (HR, 0.84; P = 0.09), and at prot ocol amendment were 18.9 and 19.6 (HR, 0.95; P = 0.78), respectively. At protocol amendment for the CMV endpoint, the oral GCV treatment eff ect was associated with baseline use of didanosine (ddI). For patients taking ddI at randomization, HR was 7.48 (P = 0.02). For patients not taking ddI, HR was 0.62 (P = 0.04). These HR were statistically diffe rent (P = 0.0006). Conclusions: In our study, 3 g/day oral GCV did not significantly reduce CMV disease incidence, but there was a suggestio n of a death-rate reduction. Furthermore, results suggest that oral GV C decreased risk of CMV disease in patients not prescribed ddI, and in creased risk in those prescribed ddI. For the CMV endpoint, our study differs markedly from the only similar study, although for the death e ndpoint, a combined analysis of studies indicated significant reductio n in death rate.