""""""""The goal of this project is to conduct translational research aimed at developing improved and novel therapies for children with HIV infection and HIV-associated malignancies. In terms of HIV infection, both antiretroviral and immunologic approaches are currently being investigated. One focus during the past year has been to continue to evaluate in Phase I/II trials the highly active protease inhibitors indinavir and ritonavir. These drugs have been found to make a major impact on the care of adults with HIV infection, but until very recently have not been studied or available for children with HIV infection. These studies helped define the pharmacokinetics, toxicity, and activity of ritonavir and indinavir in children. Based in part on short term data from one of these trials, ritonavir was approved by the FDA for pediatric use in March 1997. Data generated from our phase I study of indinavir will be also be utilized to seek FDA approval for pediatric patients. We are currently studying the long-term virological and immunological effects of therapy with these agents and in particular their ability to effect immune reconstitution. We are also investigating three novel immunomodulatory agents in HIV-infected children: recombinant IL-2, levamisole and HIV-1 immunogen vaccine. In addition to delineation of toxicity and antiviral activities, an intensive focus is directed toward assessment of quantitative and qualitative measures of immune function associated with these therapies. We have also initiated a study of the novel antiretroviral agent F-ddA (lodenosine) in children. This agent, which was developed by the NCI, has been found to have little cross-reactivity to other dideoxynucleoside reverse transcriptase inhibitors and to even retain activity in strains of HIV with a Q151M mutation that has resistance to multiple dideoxynucleosides. We are in the process of initiating a study of the immunoreconstitution achieved with a combination regimen of highly active antiretroviral therapy (HAART). A study is planned of the combination of ddI (didanosine) and hydroxyurea. In collaboration with members of the Pediatric Oncology Branch, we are also conducting studies of interferon-alpha and all-trans-retinoic acid for the treatment of HIV associated lymphoproliferative disorders, and dose-intensive chemotherapeutic regimen for treatment of non-Hodgkin's lymphoma (NHL) in HIV-infected patients. Longitudinal studies of neurocognitive function, brain imaging and immune measures in children receiving antiretroviral therapy are being conducted in addition to investigation of the pathophysiology of HIV encephalopathy. Psychosocial studies include investigation of correlates of psychosocial functioning and coping strategies in long term survivors and longitudinal examination of psychological disturbances in HIV-infected, school-aged children. HIV/AIDS-related work accounted for 100% of this project.""""""""
Showing the most recent 10 out of 11 publications
