This study has been designed with the recognition that the concurrence of alcohol use and HIV infection are escalating worldwide, and of critical concern is the significantly impairing immune responses and cognitive performance among those HIV infected individuals in their more productive years. Recognizing the involvement of the immune system in the neurobiological mechanisms that underlie cognitive impairment, we will also investigate its action, through the evaluation of platelets and platelet associated factors (i.e. serotonin, PAF, BDNF) on both immune and cognitive dysfunction. Support for this potential mechanism is based upon our preliminary findings and evidence that 1) both HIV and alcohol use affect and are affected by platelets and platelet associated factors, 2) platelets are a source of neurotransmitters and immunomodulators;3) platelet drops have been associated with HIV disease progression and 4) platelets have been proof a good peripheral model to study CNS compromise. Over the past six years, we have evaluated the deleterious effects of combined alcohol abuse and HIV infection over the neuroimmune system, in an ethnically diverse clinical sample. The proposed application will build upon our previous studies. Using an observational clinic based longitudinal study we will evaluate platelets, platelet associated factors, immune and cognitive function in four groups: hazardous and non-hazardous alcohol consuming HIV-infected subjects and hazardous and non-hazardous alcohol consuming HIV sero-negative subjects (n=540). Using standard questionnaires, a detailed sociodemographic, medical, nutritional, alcohol use and HIV medication history will be obtained. Biological measures (i.e. alcohol levels, platelet counts, serotonin, brain derived neurotrophic factors, platelet activator factor, CD4, CD8, markers or apoptosis, TNF viral load, nutrition status, biochemical profile) followed longitudinally will complement the evaluation. Cognitive function will be evaluated at baseline, 6, 12 and 18 months using a cognitive test battery that incorporates recommendations from the NIMH Workgroup on Neuropsychological Assessment Approaches in HIV. We will then establish cross-sectional and longitudinal within-subject relationships among platelets system measures, cognitive performance, and clinical status by study groups. Our long-term objectives are to extend biomedical knowledge related to mechanism mediating alcohol/HIV damage. magebocytopenia and platelet associated factors on the observations.

Public Health Relevance

Collectively, this information will broaden the scope of therapeutic interventions that might be used to enhance or restore host defense mechanisms and neuroimmune modulation that have been altered as a result of HIV infection and drinking. By increasing understanding of the new mechanistic insights related to the role of thrombocytopenia in the pathogenesis of HIV, scientist can manipulate them to therapeutic advantage.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA018095-03
Application #
8080465
Study Section
Special Emphasis Panel (ZRG1-AARR-H (02))
Program Officer
Wang, Joe
Project Start
2009-08-10
Project End
2013-11-30
Budget Start
2011-06-01
Budget End
2013-11-30
Support Year
3
Fiscal Year
2011
Total Cost
$346,438
Indirect Cost
Name
Florida International University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
071298814
City
Miami
State
FL
Country
United States
Zip Code
33199
Míguez-Burbano, Maria Jose; Espinoza, Luis; Whitehead, Nicole Ennis et al. (2014) Brain derived neurotrophic factor and cognitive status: the delicate balance among people living with HIV, with and without alcohol abuse. Curr HIV Res 12:254-64
Míguez-Burbano, María José; Espinoza, Luis; Bueno, Diego et al. (2014) Beyond the Brain: The Role of Brain-Derived Neurotrophic Factor in Viroimmune Responses to Antiretroviral Therapy among People Living with HIV with and without Alcohol Use. J Int Assoc Provid AIDS Care 13:454-60
Míguez-Burbano, María José; Rodriguez, Allan; Vargas, Mayra et al. (2014) Are Serotonin Alterations the Link between Thrombocytopenia and Poor Immune Status among HIV Infected Individuals? J AIDS Clin Res 2:
Míguez-Burbano, María José; Quiros, Clery; Lewis, John E et al. (2014) Gender differences in the association of hazardous alcohol use with hypertension in an urban cohort of people living with HIV in South Florida. PLoS One 9:e113122
Míguez-Burbano, María José; Espinoza, Luis; Cook, Robert L et al. (2013) Alcohol, Brain Derived Neurotrophic Factor and Obesity among People Living with HIV. J AIDS Clin Res 4:245
Miguez, Maria Jose; Rosenberg, Rhonda; Burbano-Levy, Ximena et al. (2012) The effect of alcohol use on IL-6 responses across different racial/ethnic groups. Future Virol 7:205-213
Míguez, María José; Burbano-Levy, Ximena; Carmona, Talita et al. (2012) Hypocalcaemia, alcohol drinking and viroimmune responses in ART recipients. Alcohol 46:763-8
Miguez, Maria Jose; Rosenberg, Rhonda; Burbano, Ximena et al. (2011) Cholesterol as a Mediator of Alcohol-Induced Risks for Respiratory Disease Hospitalizations among People Living With HIV. J AIDS Clin Res Suppl 1:
Míguez, María Jose; Lewis, John E; Bryant, Vaughn E et al. (2010) Low cholesterol? Don't brag yet ... hypocholesterolemia blunts HAART effectiveness: a longitudinal study. J Int AIDS Soc 13:25
Míguez-Burbano, María José; Lewis, John E; Fishman, Joel et al. (2009) The influence of different types of alcoholic beverages on disrupting highly active antiretroviral treatment (HAART) outcome. Alcohol Alcohol 44:366-71

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