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

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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.