The human immunodeficiency virus (HIV) epidemic is progressing at an alarming rate in developing and low- to middle-income countries. Treatment of HIV with highly active antiretroviral therapy (HAART) is frequently delayed or unavailable to many infected individuals, and consequently the prevalence of HIV-associated diseases is much higher in these countries compared to high-income countries. In southern India, many patients experience severe immunosuppression and development of neurocognitive and neuroimaging abnormalities. Preliminary studies focused on the evolution of these abnormalities reveal strong relationships between low CD4 cell count and cognitive difficulties, and associations between the volume of specific brain structures and cognitive dysfunction among patients with significant immune system suppression. However, studies have not examined the impact of severely compromised immune systems on the development of neurocognitive and neuroimaging abnormalities among non-demented patients. The purpose of this proposal is to establish a collaborative research partnership between clinical researchers at YRG Care in Chennai, India and researchers at the Brown University Center For AIDS Research to examine brain dysfunction associated with HIV. We propose to: 1) establish the investigative collaboration and conduct needs assessments, 2) develop and implement training modules focused on the assessment of cognitive function, structural neuroimaging abnormalities, and the integration of cognitive, neuroimaging, and laboratory values of disease activity, 3) collect pilot data for a subsequent R01 submission to comprehensively examine the evolution of brain dysfunction in patients with HIV. The pilot study will involve collection of cognitive, structural MRI and laboratory values of disease activity in HIV patients with significant immune system compromise. Cross-sectional and longitudinal analyses will examine the impact of HIV on cognitive and brain morphometric indices. The study will take advantage of the infrastructure currently available at the YRG Care in Chennai, India, and the clinical and research infrastructure established at the Brown CFAR. The developmental grant will yield significant advances in the understanding of brain disorders associated with HIV.
