Pneumocystis pneumonia is a major cause of death for AIDS patients. Over the past 20 years almost nothing has been learned about the causative organisms, Pneumocystis carinii. In a collaborative effort, an in vitro system was established that identified trimetrexate as a potent dinydrofolate reductase inhibitor for pneumocystis, far more potent than currently available drugs. In a clinical trial for AIDS patients with pneumocystis pneumonia, trimetrexate alone and trimetrexate with sulfa gave excellent response rates when used as initial therapy and when used for patients who had failed conventional therapy. Toxicity was minimal. A large multicenter trial to compare trimetrexate with conventional therapy started 8/87. The importance of this project is the identification of new drugs to treat a major cause of death among AIDS patients.
