Understanding the Progression of HIV-Associated Neurocognitive Disorder (HAND) through cardiovascular disease and markers of inflammation

Despite recent advancements in healthcare that allow people living with HIV (PLWH) and healthy people living with comorbid conditions, such as obesity, diabetes, and heart disease, to live longer, new consequences arise, as people now live for longer durations of time with these diseases and comorbid conditions. Research has suggested that presence of diseases such as obesity, diabetes, and heart disease in mid-life could be predictive of cognitive decline development later on in life through several interconnected pathogenic mechanisms, each which could potentially be exacerbated by HIV infection. For instance, systemic inflammation caused by obesity, cardiovascular disease development, metabolic dysregulation, and HIV infection could eventually lead to neuroinflammation, development of pathogenic vascular plasticities which result from a heightened inflammatory state, and secretion of pro-inflammatory cytokines, all which ultimately culminate in cognitive decline. Eventually, this leads to a synergistic effect in PLWH, as additional cardiac complications occur in this cohort of people due to previously harsh antiretroviral therapy management, development of myocarditis, endothelial damage, and eventual heart failure. Overall, each of these processes contribute to pathogenic pathways which lead to cognitive decline, and potential development of HIV-associated neurocognitive disorder (HAND) in PLWH. This essay aims to describe, in detail, the interplay of the aforementioned mechanisms, and to also examine if single-nucleotide polymorphisms of the cyclic AMP (cAMP) element-binding protein CREB1, which has been implicated in higher rates of cognitive decline in healthy adults, exist at significant levels in PLWH. Results show no significant interaction between alleles of CREB1 and decline status in this cohort of subjects, however it is important to continue research in this area, due to its public health implications. This area of research is of high public health significance, because individuals living with these conditions may eventually suffer from a lower quality of life as a result of comorbid conditions. Additionally, it addresses current gaps in research by attempting to describe a causal pathway of how cognitive decline progresses in HIV-infected vs. healthy individuals, what factors (i.e. environmental, genetic) could contribute to this progression, and if/how they can be managed to ensure better quality of life