Studies in the prophylaxis of herpes infections in severely immunocompromised patients using acyclovir

That acyclovir is effective therapeutically in herpes simplex virus (HSV) and herpes zoster (VZV) infections in immunocompromised patients has been established [13]. This paper reviews our subsequent studies in prophylaxis of herpes group infections in a high risk group of patients suffering from acute leukaemia. In study 1 we randomised HSV seropositive (greater than or equal to 1:8) patients to receive intravenous acyclovir or placebo. In this stratified study bone marrow transplant (BMT) recipients were completely protected from HSV infections by acyclovir compared with a 50% failure rate for those on placebo. There was significant protection also in the non-BMT group [8]. In study 2 oral acyclovir prophylaxis failed to provide complete protection in BMT recipients despite the achievement of apparently adequate blood levels. In study 1 the secretion of EBV in saliva before and during the trial gave inconclusive results. In each of the first two studies one patient on "active" acyclovir developed a cytomegalovirus (CMV) infection. Thus, at the dosage of drug used, prophylaxis of CMV was unsuccessful suggesting that claims of therapeutic efficacy are unlikely to be supported in controlled trials. Study 3 is current and concerns the pharmacokinetics of an acyclovir prodrug (BW 134U) taken by mouth. This drug is near 100% absorbed and achieves approximately twice the level of active acyclovir in vivo, following conversion by adenosine deaminase (ADA), in normal volunteers.