Human Immunodeficiency Virus (HIV) is a significant public health concern in the United States. The Center for Disease Control (CDC) estimates that over one million individuals in the United States are currently living with the disease, with thousands of new cases each year. In the United States survival rates associated with HIV infection have improved dramatically since the introduction of highly active antiretroviral therapy (HAART), which permits greater control of viral migration into the brain post-infection.1-4 However, nearly half of all individuals with HIV exhibit cognitive dysfunction, despite advances in highly active antiretroviral therapy (HAART). 5-6 Furthermore, the onset and progression of cognitive dysfunction is variable among HIV+ individuals.7-13 Increased importance has therefore been placed on understanding the role that comorbid conditions play in the etiology of HIV-related neurocognitive in the HAART era. A recent NIH- funded study investigated the impact of early life stress (ELS), which is highly prevalent in HIV+ individuals, on structural brain integriy and neurocognitive performance in a group of HIV+ individuals and healthy controls.14 Results of this study revealed reduced grey matter integrity and neurocognitive dysfunction in HIV+ individuals with high levels of ELS. Due to the robustness of these findings, it is crucial that we develop a more comprehensive understanding of the impact that ELS has on the brain of individuals with HIV. The proposed study will investigate the combined effects of HIV and high levels of ELS on white matter (WM) microstructural integrity using diffusion tensor imaging (DTI) which offers a more direct method of examining brain dysfunction than traditional structural magnetic resonance imaging (MRI). This study will examine DTI scalar metrics fractional anisotropy and mean diffusivity, and neuropsychological performance among a cross-sectional sample of HIV+ individuals with prior history of high levels of ELS (= 3 ELS events; ELS+) and demographically similar HIV+ individuals with no ELS (0 events; ELS-) to identify the long term impact of ELS on the brain. A sample of 30 HIV+/ELS+ individuals will be compared to 30 HIV+/ELS- individuals using a 3T MRI with DTI and neuropsychological evaluation. This research will be the first to utilize DTI scalar metrics in conjunction with neuropsychological evaluation to detect WM microstructural integrity and cognitive deficits in individuals with comorbid HIV and ELS. The long-term objective of this study is to develop a more comprehensive model of the mechanisms through which high ELS impacts neurocognition in HIV patients to increase our ability to assess and treat HIV related neurocognitive dysfunction.
Prior research has revealed neural abnormalities and cognitive dysfunction in individuals with human immunodeficiency virus (HIV). There is, however, a high rate of variability in this population, with some individuals experiencing minimal dysfunction and others demonstrating significant deficits. Numerous studies have provided evidence that this variability can often be explained by viral and host factors. However, little research has examined the impact of early life stress (ELS), a prevalent host factor in HIV+ individuals, on cognitive and brain structural variability. Evidence from a recent NIH-funded study examining the impact of HIV and comorbid ELS revealed that high levels of ELS (=3 ELS events) in HIV+ individuals negatively impacts neurocognitive function and grey matter volume, however the impact of this comorbidity has not been examined in white matter integrity. Therefore, we currently lack a comprehensive understanding of the impact of ELS on the brains of HIV+ individuals. The proposed study will be the first to integrate neuropsychological assessment and diffusion tensor imaging to examine mechanisms of structural and functional dysfunction following ELS exposure in HIV+ individuals.
