comparison of two dosage regimens of oral dapsone for prophylaxis of pneumocystis carinii pneumonia in pediatric hiv infection

Conditions: Pneumonia, Pneumocystis Carinii; HIV Infections

Summary: primary: to compare the toxicity of daily versus weekly dapsone in hiv-infected infants and children; to study the pharmacokinetics of orally administered dapsone in hiv-infected infants and children. secondary: to obtain information on the rate of pneumocystis carinii pneumonia ( pcp ) breakthrough in children receiving two different dose regimens of dapsone. prophylaxis for pneumocystis carinii pneumonia ( pcp ) is recommended for all hiv-infected children considered to be at high risk. approximately 15 percent of children are intolerant to trimethoprim / sulfamethoxazole, the first choice drug for pcp prophylaxis. since many children are also unable to take or tolerate aerosolized pentamidine, dapsone is a second choice for pcp prophylaxis. the most favorable dose regimen for dapsone has not been established.

prophylaxis for pneumocystis carinii pneumonia ( pcp ) is recommended for all hiv-infected children considered to be at high risk. approximately 15 percent of children are intolerant to trimethoprim / sulfamethoxazole, the first choice drug for pcp prophylaxis. since many children are also unable to take or tolerate aerosolized pentamidine, dapsone is a second choice for pcp prophylaxis. the most favorable dose regimen for dapsone has not been established. ninety-six hiv-infected infants and children who are intolerant to trimethoprim / sulfamethoxazole ( tmp / smx ) are randomized to receive oral dapsone in a lower dose once daily or at a higher dose once weekly. treatment continues until the last patient enrolled has received at least 3 months of therapy. blood samples are drawn between weeks 4 and 8, at weeks 12 and 24, and every 3 months thereafter during dapsone administration.

Eligibility criteria:
inclusion criteria concurrent medication: allowed: * rifampin and rifampin derivatives for up to 1 week during the study. * rifabutin or other drugs that could alter dapsone metabolism (if prescribed by the child's primary care physician). patients must have: * evidence of hiv infection. per amendment 11/16/95: * children who require prophylaxis. (was written - risk of developing pcp.) * known intolerance to tmp / smx. * consent of parent or guardian. patients entering this study may be co-enrolled in other actg pediatric studies. exclusion criteria co-existing condition: patients with the following symptoms and conditions are excluded: * glucose-6-phosphate dehydrogenase deficiency. * known allergy to dapsone. concurrent medication: excluded: * rifampin, rifampin derivatives, or oxidant drugs for more than 1 week. patients with the following prior conditions are excluded: * serious or life-threatening reactions to tmp / smx (e.g., anaphylaxis, stevens-johnson syndrome, hypotension) that would contraindicate therapy with sulfa drugs. prior medication: excluded: * prior dapsone. * rifampin, rifampin derivatives, or oxidant drugs within 1 week prior to study entry. * tmp / smx within 7 days prior to study entry (and toxicity must be clearly resolving). prior treatment: excluded: * rbc transfusion within 4 weeks prior to study entry.

Keywords: pneumonia, pneumocystis carinii dapsone acquired immunodeficiency syndrome aids-related complex drug administration schedule