The goal of this research is to improve our understanding of the treatment and prevention of Pneumocystis carinii pneumonia (PCP) in men, women and children with HIV 1 infection. The specific objectives are to study: 1) the efficacy, toxicity, and pharmacokinetics of high dose, aerosolized pentamidine prophylaxis in adult patients, 2) the pharmacokinetics of parenteral pentamidine in asymptomatic, HIV 1 infected men and women who are at risk for the development of PCP, 3) the pharmacokinetics of prophylactic aerosolized and parenteral pentamidine in asymptomatic, HIV 1 infected children, 4) the pharmacokinetics of parenteral pentamidine in children who are being treated for acute PCP. In the adult study, 150 patients will receive either 600 mg once-monthly or 300 mg once-monthly (double-blind) of aerosolized pentamidine prophylaxis. End point analysis includes occurrence of PCP, toxicity and death. In a subset of 20 of these patients, an intensive study of toxicity and pharmacokinetics will be carried out using serial pulmonary function testing and measurement of pentamidine concentration in bronchoalveolar lavage fluid and plasma. The pharmacokinetics of pentamidine will be studied in an additional 80 individuals in the following categories: Group 1: 15 women who are being treated for PCP with intravenous pentamidine, Group 2: 10 volunteer, asymptomatic HIV+ women who are at risk for PCP, Group 3: 10 volunteer asymptomatic HIV men (control group) who are at risk for PCP, Group 4: 15 children, age < 13 years, who are receiving treatment for PCP with intravenous pentamidine, Group 5: 15 asymptomatic HIV+ children who are receiving once monthly intravenous prophylaxis, Group 6: 15 HIV+ asymptomatic children who are receiving once monthly aerosolized prophylaxis for pentamidine. Serial blood and urine specimens will be obtained according to the enclosed protocols, pentamidine will be assayed using high performance liquid chromatography, and the kinetics will be calculated using standard modelling techniques.
