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Ten marrow transplant recipients with biopsy-proven cytomegalovirus pneumonia were treated with the acyclic nucleoside analog 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine (BW B759U). Viruria and viremia ceased after 4 days of treatment in all patients with cultures initially positive from these sites. Cytomegalovirus was eliminated from respiratory secretions after a median of 8 days. Despite this antiviral effect, only one patient survived the pneumonia. Quantitative cultures of lung tissue before and after treatment confirmed that therapy with BW B759U was associated with substantial antiviral activity, with a mean decrease in viral titers of more than 99.99% after treatment. Neutropenia developed in three patients when mean peak and trough plasma levels exceeded 50 and 10 mu mol/L, respectively, but no other toxicity was seen. BW B759U is the first antiviral agent showing consistent activity against cytomegalovirus in vivo, and it should be evaluated in the earlier management of cytomegalovirus infections after marrow transplantation and in serious cytomegalovirus infections in other immunocompromised patients.

Acyclovir tolerance has been explored in a broad range of human populations and dosage regimens with intravenous, topical, and oral formulations. Phase I pharmacokinetic/tolerance studies assured safety in special populations at unique risk of complicated herpes infections who were simultaneously at increased risk of toxicity to anti-DNA chemotherapeutic agents. Further safety evaluations accompanied placebo-controlled Phase II studies in infected patients who represent future users of acyclovir. These studies confirm acyclovir as the safest antiherpes agent to be explored in clinical studies to date.