PREVENTION OF SERIOUS BACTERIAL IN HIV CHILDREN

本研究假设阿托伐酮/阿奇霉素联合治疗在预防CD4淋巴细胞群减少的hiv感染儿童的严重细菌感染方面将相当于或优于甲氧苄啶/磺胺甲恶唑。这两种预防方案的长期安全性和耐受性也将作为研究的一部分进行评估。在对是否使用过TMP/SMX和/或IVIG进行分层后，受试者被随机分为两组：TMP/SMX （5mg /kg/天）或微粉阿托伐酮（30mg /kg/天）加阿奇霉素（5mg /kg/天）。如果观察到严重的与治疗相关的毒性，则需要交叉使用替代药物方案。正在通过监测严重细菌感染的发生或PCP的突破来评估抗菌方案的疗效。当达到严重的细菌感染终点（确定第二次感染）时，受试者将被交叉到替代研究药物方案。受试者将接受研究药物，直到最后一名受试者完成2年的随访。前30名受试者进行了药代动力学分析，以帮助确保先前建立的阿奇霉素和阿托伐酮的血药浓度不受两种药物联合使用的显著影响。

This study hypothesizes that the combination of atovaquone/azithromycin will be equivalent to or superior to trimethoprim/sulfamethoxazole for the prevention of serious bacterial infection in HIV-infected children with depleted CD4 lymphocyte populations. The long-term safety and tolerance of the two prophylactic regimens will also be evaluated as part of the study. After stratifying for previous use of TMP/SMX and/or IVIG, subjects were randomized to one of two arms: TMP/SMX (5 mg/kg/day) or micronized atovaquone (30 mg/kg/day) plus azithromycin (5 mg/kg/day). Cross-over to the alternative drug regimen was to occur if a serious treatment-related toxicity was observed. The efficacy of the antibacterial regimens is being evaluated through monitoring the occurrence of serious bacterial infections or PCP break-through. When a serious bacterial infection endpoint ( a second infection is identified) is reached, subjects will be crossed over to the alternative study drug regimen. Subjects will receive study drug until the last subject enrolled has completed 2 years follow up. The first 30 subjects were to have had a pharmacokinetics profile performed to assist in insuring that previously established blood concentrations of azithromycin and atovaquone were not significantly affected by the administration of the two drugs in combination.