CLINICAL-EXPERIENCE WITH ATOVAQUONE ON A TREATMENT INVESTIGATIONAL NEW DRUG PROTOCOL FOR PNEUMOCYSTIS-CARINII PNEUMONIA

The clinical experience of human immunodeficiency virus (HIV) + patien ts treated with oral atovaquone for acute Pneumocystis carinii pneumon ia (PCP) under a Treatment investigational New Drug (IND) protocol (mi ld or moderate PCP) and an Open-Label Study protocol (severe PCP) was evaluated. A total of 940 patients intolerant of or unresponsive to tr imethoprim-sulfamethoxazole were enrolled from private practices, clin ics, and institutional HIV treatment centers in the United States, Dem ographics data and the history and severity of PCP were collected at e nrollment, The number of therapy days, adverse experiences, clinical r esponse to therapy, and mortality were collected at day 21. Reporting of serious, unexpected adverse experiences attributable to therapy was required. Of the 760 (96%) patients with mild to moderate disease for whom follow-up observation was complete, 591 (78%) responded clinical ly to treatment, 177 patients (23%) discontinued treatment prematurely , and 50 patients (7%) died. Of the 140 patients (95%) with severe PCP with follow-up data, 79 (56%) responded to treatment, 45 (32%) discon tinued treatment early, and 53 patients (38%) died. Adverse events tha t resulted in temporary or permanent discontinuation of therapy includ ed diarrhea, vomiting, elevated liver enzyme levels, nausea, and fever . No serious unexpected adverse events attributable to the drug were r eported. The treatment IND mechanism enabled a large number of patient s with acute PCP to be treated with this experimental therapy while th e drug was under regulatory view.