A double-blind randomized placebo trial on very high doses of acyclovir in weakly symptomatic HIV-patients.

Herpesvirus infections are thought to be cofactors of the human immunodeficiency virus (HIV) disease, and high concentrations of acyclovir (ACV) are active on all herpesviruses. Because ACV was shown to delay the cytopathic effect of HIV in vitro, we evaluated the effect of intermittent high doses of ACV in mildly symptomatic HIV-patients in a randomized double-blind placebo-controlled trial with a 4-month treatment period. A total of 30 CDC II and III patients were enrolled; 24 (80%) completed the study. Placebo and ACV were given once a week in a 3-h infusion with 1 g oral probenecid. Each dose of ACV was 50 mg/kg. Pharmacokinetic data were obtained from patients of the preliminary open study. The obtained concentrations were effective against both herpesviruses and HIV: peak concentrations were 197 and 11 mumol/l in serum and CSF, respectively; the CSF:serum ratio of the areas under the curve was 82%. Two patients with placebo acquired hairy leukoplakia and detectable antigenemia vs. none in the ACV group (p = 0.23). T-helper cell count over the 4-month period decreased in the placebo group while it increased in the ACV-treated group (mean of change = -105 c/microliters vs. +68 c/microliters; p = 0.06). beta 2-microglobulin increased with placebo and did not with ACV (mean of change = +0.63 mg/l vs. -0.27 mg/l, p less than 0.025). Only one patient had, at one time, transient elevation of creatinemia related to ACV. We concluded that weekly high doses of ACV were able to delay the progression of some significant markers of HIV disease. Thus, preventive/prophylactic treatment of herpesvirus infections could be useful in mildly symptomatic HIV patients. Further larger trials using a more feasible treatment are warranted.