THE EVALUATION OF IMMUNE DYSREGULATION DURING ALCOHOL WITHDRAWAL TREATMENT AND EARLY REMISSION AMONG HIV INFECTED ALCOHOLICS

Abstract



BACKGROUND Immune activation (IA) is a hallmark of HIV progression and result in end- organ diseases. HIV progression markers: - viral load - biomarkers of chronic inflammatory - microbial translocation and immune activation Alcohol withdrawal and detoxification induce disturbances in the stress hipothalamo-pituitary axis (HPA), sympathetic-adrenomedullary system (SAM) and immune response. - Alcohol abuse associated with more rapid HIV progression by inducing immune activation - Alcohol induces neuroinflammatory processes - Alcohol withdrawal is associated with an increased CD4+ T cell counts Potential protective markers Neurosteroids (dehidroepiandro-sterone and its sulfate, DHEA and DHEA-S) have anti-stress properties, protective role in detrimental effects of stress hormones, altered cognitive functions, have anti-inflammatory related to higher VL and shift from Th1 to Th-2. Decreased level of steroid precursor, cholesterol, was find as predictive factors of relapse in detoxified cocaine HYPOTHESIS 1: alcohol withdrawal-induced HPA and SAM dysregulations are the major mediator of viral control, immune responses and neurocognitive impairment (NCI) in HIV persons 2: HPA/SAM dysregulations effects are lasting the 4 weeks follow up after alcohol detoxification APPROACH - Study sample = 50 ART naive HIV+ persons who are entering alcohol addiction treatment - All patients will complete 3 assessments and each included neurocognitive assessment and blood sampling TIME LINE -------------------------------------------------------------------------------------------------------- \ (Day #1) • Clinical examination, neurocognitive assessment, blood sampling, urine J Viit 2 • Clinical examination, neurocognitive assessment, blood sampling, medical charts review (Day #5-10) j \ Visit 3 • Clinical examination, neurocognitive assessment, blood sampling, urine drug test (Day #30) J OUTCOMES Primary outcome: HIV RNA in blood plasma Secondary outcomes: • Neurocognitive performance (z-score) • Stress response system biomarkers (HPA, SAM dysregulation) AIMS dysregulations to virologic control and NCI during detoxification Aim 2: To determine the mechanism of impaired viral regulation by linking HPA/SAM axis dysregulation Aim 3: To explore the normalization of HPA/SAM after 4 weeks of abstinence linked to virologic control and NCI improvements METODS Markers of immune activation: • sCD14 (macrophage activation marker, microbial translocation indicator) • MCP-1 (CCL2, monocyte activation marker) • IL-6 (chronic inflammation marker) • Lipopolysaccharide, LPS (microbial translocation indicator) • Activated T-cells: CD4+ and CD8+ Markers of stress response system: HPA axis • ACTH, Cortisol • Cholesterol, DHEA, DHEA-s SAM system • Epinephrine, Norepinephrine • NPY Markers of immune response • Th1 cells (fight intracellular bacteria): TNF alpha • Th2 cells (combat extracellular bacteria): IL-10 IMPLICATIONS - It determines if alcohol withdrawal disrupt HIV control acutely by inducing dysregulations of HPA/SAM and immune systems - It evaluates a potential risks of development of NCI during alcohol withdrawal and early remission in HIV- infected alcoholics - It examines HIV progression and markers of immune activation and stress response system The content is solely the responsibility of the authors. The authors have no conflicts of interest to declare.

M Vetrova

First Pavlov State Medical University of St. Petersburg

O Toussova

First Pavlov State Medical University of St. Petersburg

T Yaroslavtseva

First Pavlov State Medical University of St. Petersburg

V Palatkin

First Pavlov State Medical University of St. Petersburg

E Blokhina

First Pavlov State Medical University of St. Petersburg

E M Krupitsky

First Pavlov State Medical University of St. Petersburg

E E Zvartau

First Pavlov State Medical University of St. Petersburg

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Copyright (c) 2016 Vetrova M., Toussova O., Yaroslavtseva T., Palatkin V., Blokhina E., Krupitsky E.M., Zvartau E.E.

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