Safety of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in patients with human immunodeficiency virus infection

Abstract

The compound 9-(2-phosphonylmethoxyethyl)adenine (PMEA) is a potent inhibitor of a number of viruses in vitro such as human immunodeficiency virus types 1 and 2, herpes simplex virus types 1 and 2, hepatitis B virus, cytomegalovirus, and Epstein-Barr virus. PMEA also proved to be effective in vivo against feline immunodeficiency virus in cats and simian immunodeficiency virus in rhesus monkeys. In an open, non-placebo-controlled trial, the safety of weekly doses of PMEA in 10 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was studied for a period of 11 weeks. CD4+ T-cell counts at baseline were between 10 and 450/mm(3). The drug was administered intravenously at a dose of 1000 mg. No serious side-effects were seen. On one occasion one patient showed alanine aminotransferase and aspartate aminotransferase levels 5 times higher than the upper limit of normal and another patient showed on one occasion aspartate aminotransferase levels 5 times higher than the upper limit of normal. In another patient serum amalyse levels increased, on one occasion 1.5 times above the upper limit of normal. An improvement in general well-being was reported by all patients. For patients with a CD4+ T-cell count > 100/mm(3) at baseline, the CD4+ T-cell count increased from a mean of 283/mm(3) at baseline to a mean of 448/mm(3) at the end of the study. Repeat infusions of PMEA at a dose of 1000 mg were safe and well tolerated. Our results suggest that PMEA, administrated according to this treatment schedule, may be effective in treating patients with human immunodeficiency virus infection.

Effect of Weekly Adefovir (PMEA) Infusions on HIV-1 Virus Load: Results of a Phase I/II Study

“…In contrast to a previous study [17] no hepatotoxicity was observed in this study. In general, laboratory abnormalities were primarily characterized by a decline in neutrophil counts in three of the nine patients at the end of the study and will be a reason for concern in future clinical trials with adefovir.…”

“…In a previous study we sought to determine the safety and tolerance of weekly doses of adefovir, administered intravenously at a dose of 1000 mg in patients with AIDS or AIDS-related complex [17]. During a period of 12 weeks no serious clinical toxicity was observed in that study.…”

“…The patients received 1000 mg adefovir in a 30 ml saline buffered solution in less than 10 minutes by infusion. In case of elevated ALT and/or ASAT levels, as seen in a previous study [17], or other laboratory abnormalities, therapy was resumed at half the original dose. Persistent laboratory abnormalities led to permanent discontinuation of adefovir therapy.…”