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Determination of a biomarker profile associated with neurocognitive disorders in HIV-1 patients

Grant number: 15/13853-7
Support type:Regular Research Grants
Duration: December 01, 2015 - May 31, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Jose Ernesto Vidal Bermudez
Grantee:Jose Ernesto Vidal Bermudez
Home Institution: Instituto de Infectologia Emílio Ribas (IIER). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers:Augusto Cesar Penalva de Oliveira ; Camila Malta Romano ; Jorge Simão do Rosário Casseb

Abstract

The introduction of highly active antiretroviral therapy (HAART) resulted in decrease of the incidence of HIV-Associated Dementia (HAD).However, in the past few years long-term infected patients, including those systemically controlled individuals, began to complain about memory problems, slow-thinking and difficulties in concentration. Neurological disorders associated with HIV (HAND) affect quality of life, productive working function and adherence to HAART, which can in turn affect the control of systemic infection. Many potential markers have been studied, but so far none of them proved to be useful in clinical practice alone, so it is necessary to determine an objective, quantitative, and scalable profile markers to HAND. Therefore, the aim of this study is to evaluate possible virological, immunological and brain injury markers in 150 patients. Of these, 120 are seropositive for HIV being 30 diagnosed with Asymptomatic Neurocognitive Amendment, 30 diagnosed with Disorder mild / moderate, 30 Neurocognitive diagnosed with HIV-associated dementia and 30 without any neurocognitive disorders (control group 1). The remaining 30 must show negative HIV serology and no neurocognitive disorders (control group 2).To determine virological markers, the proposal is to quantify the viral load of HIV-1 and HERV-K in CSF, which is highly expressed in HIV-1 infected individuals. To trace the host immune response profile, lipopolysaccharide levels will be searched in plasma as well as aspecific panel of cytokines in cerebrospinal fluid. Samples with detectable HIV viral load in the CSF of patients who also exhibit detectable plasma viral load will also be sequenced. Finally, constituent proteins of neurofilaments will be searched in CSF as brain injury indicators. So far were collected approximately 40 samples and the immunophenotyping was performed in the CSF of some patients to determine the most prevalent cell populations, as well as their level of activation. Preliminary analysis showed that patients with ANI have significantly higher number of activated lymphocytes and monocytes compared to HIV- control group and also a reduced number of CD4 + T cells when compared to HIV+ control group. (AU)