Background: Dapsone is an alternative drug for prophylaxis of Pneumocystis carinii pneumonia (PCP), but there are few data about its toxicity or efficacy in HIV-infected children.

Methods: This was a randomized, open-label, multicenter study of daily vs. weekly dapsone in HIV-infected children intolerant to trimethoprim/ sulfamethoxazole (T/S) who required PCP prophylaxis. 94 children were randomized to 1 mg/kg daily (later 2 mg/kg) or 4 mg/kg weekly of oral dapsone. Hematologic, hepatic and clinical toxicities, survival, and the incidence of laboratory-proven PCP were monitored, and steady-state pharmocokinetic (PK) studies were performed.

Results: Early PK data indicated that 1 mg/kg daily dosing did not achieve peak drug concentrations and AUCs equivalent to those seen with the standard 100 mg daily adult dosing. The dose was therefore increased to 2 mg/kg in those already randomized, and new patients entering on daily drug received the higher dose.

Early (2 week) red cell toxicity was significantly greater in the daily than the weekly group, but this was not clinically significant, and recovery occurred: long-term, Grade 3/4 hematologic toxicity was not significantly different between the groups. Deaths while on study drug or within 3 months of stopping were significantly (p=.037) greater in the daily (8) than the weekly(2) group, although causes of death were diverse, multiple, and of the expected type for children with AIDS. Allergic-type rashes occurred in both groups (16% over-all, p=.78), usually in the first 1-5 weeks. Having a rash while on prior T/S did not appear to predispose to rash with dapsone.

10 cases of proven PCP occurred on dapsone. While this was not enough to demonstrate significant differences between the dosing groups, 6 of the cases occurred in the weekly group (9.5 cases/100 patient-years) and 3 in the children receiving 1 mg/kg daily (22.0 cases/100 PY). Only one case occurred in a child receiving 2 mg/kg daily (2.0 cases/100 PY).

Conclusion: Weekly dapsone at a dose of 4 mg/kg caused significantly less acute red-cell toxicity than daily dapsone. Although hypersensitivity-type rashes were observed with both regimens, prior rash on T/S did not appear to predispose. Finally, while not statistically significant, daily dapsone at 2 mg/kg appeared to be more protective against PCP than weekly dapsone at 4 mg/kg, and the 2 mg/kg daily dose appeared to protect better than 1 mg/kg.