STUDY OF HIGH DOSE LOPINAVIR/RITONAVIR IN HIV INFECTED PEDIATRIC SUBJECTS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。具体目的：确定高剂量LPV/r治疗组1 （400/ 100mg /m2 PO Q12H）和组2 （480/120mg/m2 PO Q12H）并发NNRTI治疗的安全性和耐受性；评估沙奎那韦（750mg/m2或1200mg /m2 PO Q 12h）联合LPV/r在儿童和青少年中的安全性和耐受性（步骤2和步骤3）；估计LPV/r和沙奎那韦在接受联合抗逆转录病毒治疗的有蛋白酶抑制剂经历的hiv感染儿童和青少年中的药代动力学参数。艾滋病毒是一种慢性感染，需要终生治疗，因为目前的药物无法治愈。治疗的目标是长期控制HIV复制，以预防或逆转HIV相关症状或免疫系统抑制。三种或三种以上抗逆转录病毒药物的联合治疗优于仅使用两种抗逆转录病毒药物的单一治疗，目前推荐用于治疗艾滋病毒感染患者的三联药物治疗。有效的多药治疗可以减少病毒复制，将血浆病毒载量降低到定量或敏感试验（BLQ）以下，逆转HIV感染症状，改善生长，并改善免疫系统功能，包括增加CD4+细胞计数，减少CD8+细胞计数，提高对疫苗接种的反应。虽然有效的治疗方案最初可以将大多数HIV感染者的病毒载量降低到低于测定定量限制，但30%至80%的治疗对象将在治疗方案失败并在一年内重新检测到血浆病毒。在一些受试者中，失去对艾滋病毒复制的控制可能是良性的，他们将保持CD4+细胞计数持续高或上升，没有机会性感染的风险，也没有艾滋病毒感染的症状。然而，在其他受试者中，血浆病毒血症的复发可能与CD4+细胞计数减少、耐药病毒的选择以及HIV症状或机会性感染的复发有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims: To determine the safety and tolerability of high dose LPV/r in Group 1 (400/100 mg/m2 PO Q12H) and Group 2 (480/120mg/m2 PO Q12H) with concurrent NNRTI treatment; to evaluate the safety and tolerability of saquinavir (750mg/m2 or 1200 mg/m2 PO Q 12 H) in combination with LPV/r in children and adolescents (Step 2 and Step 3); To estimate pharmakokinetic parameters for LPV/r and saquinavir in protease inhibitor experienced HIV-infected children and adolescents receiving combination antiretroviral regimens. HIV is a chronic infection, which requires life-long therapy, since current drugs are not curative. The goal of therapy is long-lasting control of HIV replication to prevent or reverse HIV-related symptoms, or immune system suppression. Combination therapy with three or more antiretroviral medications is better than therapy with monotherapy with only 2 antiretrovirals, and triple-drug therapy is currently recommended for treatment of patients with HIV infection. Potent multi-drug therapy can decrease virus replication, reduce plasma virus load to below limits of quantitation or sensitive assays (BLQ), reverse symptoms of HIV infection, improve growth, and lead to improved immune system function, including increased CD4+ cell count, decreased CD8+ cell count, and improved response to vaccination. While potent regimens can initially reduce virus load to below assay quantitation limits in the majority of persons with HIV infection, 30% to 80% of treated subjects will have regimen failure and return of detectable plasma virus within one year. Loss of control of HIV replication can be benign in some subjects, who will have sustained high or rising CD4+ cell counts, no risk of opportunistic infection, and no symptoms of HIV infection. However, in other subjects, return of plasma viremia may be associated with a decrease in CD4+ cell count, selection of drug-resistant virus, and return of symptoms of HIV or opportunistic infection.