CLINICAL TRIAL: IMPAACT P1066 (VERSION 10) A PHASE I/II, MULTICENTER, OPEN-LAB

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT There is an acute medical need for novel and potent antiretroviral therapy for HIV-infected patients who are experiencing resistance, suffer from toxicities on other possible regimens, or are failing their current antiretroviral regimen. These patients are often heavily pre-treated and have very limited or no remaining therapeutic options. The purpose of this pediatric study is to gain dosage, short and long term safety data, intensive and population PK data, drug interactions, and efficacy experience with raltegravir in HIV-1 infected children with which to guide potential usage in children ages two through adolescence. IMPAACT P1066 is a Phase I/II, multi-center, open-label, noncomparative study of approximately 120 to 140 HIV-1 infected children and adolescents ages =2 years to 1000-fold selectivity over other phosphotranferases, including the structurally related enzyme HIV-1 RNase H and the human DNA polymerases, a, ¿, and (IC50 values 50 ¿M). The antiretroviral potency of raltegravir (IC95 of 33 ¿ 23 nM; 50% human serum) measured in vitro is comparable to many clinically efficacious antiretroviral therapeutics. Inhibition of HIV-1 replication is shown to be a result of raltegravir interference with integration. Preclinical data, including in vitro inhibition assays and safety assessment, suggest that raltegravir has the promise to be a clinically safe and effective integrase inhibitor. In addition, raltegravir has been shown in Phase II and III clinical studies, to be generally well tolerated and has demonstrated potent efficacy in both treatment-na¿ve and treatment-experienced patients with triple-class resistant virus.