Melanie Gasper, PhD
Nominated From: University of Washington
Research Site: Peru
Research Area: Infectious Disease
Primary Mentor: Joseph Zunt
Immune correlates of central nervous system-immune reconstitution inflammatory syndrome (CNS-IRIS) development in patients with and without HIV infection
HIV dramatically alters the ability of immune cells to contain infection with other pathogens, leading to an increase in both active opportunistic infections and resultant death in HIV coinfected individuals. In addition, coinfection cases produce unique complications regarding the clinical management of each disease in the context of the other. For example, immune reconstitution inflammatory syndrome (IRIS) is an inflammation-driven cause of deterioration in HIV-infected patients following the initiation of antiretroviral therapy (ART) for HIV treatment and subsequent restoration of the immune response (against coinfecting pathogens). Life-threatening neurological involvement, including meningitis, can occur during IRIS, necessitating a delay in ART treatment for immunocompromised patients during coinfection to reduce the likelihood of inducing IRIS. In order to better understand immune correlates of CNS-IRIS development, this proposal includes the following specific aims:
1. Determine the presence and activation status of innate cells in cerebrospinal fluid and peripheral blood cells of patients who do and do not develop CNS-IRIS.
2. Determine the presence and phenotype of antigen-specific lymphocytes in peripheral blood and cerebrospinal fluid of coinfected patients who do and do not develop CNS-IRIS.
Because CNS-IRIS is an immune-mediated disease, a thorough understanding of immune parameters associated with TBM-IRIS would provide rational approaches for developing immune-based prediction of clinical outcomes and, importantly, potential clinical interventions that would allow simultaneous treatment of the opportunistic infection and HIV.