This is a Phase II/III randomized trial in HIV-infected infants and children requiring PCP prophylaxis. Subjects will receive TMP/SMX 5 mg/kg/day, or micronized atovaquone, 30 mg/kg/day plus azithromycin 5 mg/kg/day. Both arms will have matching placebos. Subjects will be evaluated for safety and tolerance of the study drugs, and will be tested for equivalence of the antibacterial agents by monitoring for occurrence of serious bacterial infections. New guidelines have been established for initiation of PCP prophylaxis in children with HIV infection that take into account age appropriate CD4 counts. TMP/SMX remains the drug of choice for PCP prophylaxis, but drug sensitivity may limit its use. The efficacy of alternative therapies recommended for children (oral dapsone and IV or aerosolized pentamidine) is undetermined. Atovaquone has been demonstrated to be as efficacious as IV pentamidine and safer than TMP/SMX in adults. HIV infected children are at increased risk for serious bacterial infections, thought to be secondary to B-cell dysfunction early in the course of HIV infection. Azithromycin, an azalide with an extended half- life and broad antimicrobial spectrum, is an attractive prophylactic agent for use in children with HIV infection because of its record of relative safety and its once daily dosing regimen. Crossover to alternative study drug regimen will occur for either arm if a serious treatment-related toxicity is observed or if a serious bacterial infection endpoint is reached. This study is open to enrollment. There have been 286 patients accrued nationwide out of a target of 690.
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