Heavy alcohol consumption in an HIV-infected person may accelerate HIV disease progression and end organ disease with one leading explanatory pathway being via enhanced microbial translocation and inflammation/altered coagulation. Heavy alcohol consumption and HIV infection are both causes of microbial translocation, the process by which bacterial products leak across the gastrointestinal membrane with resultant destructive immune activation. Alcohol can lead to microbial translocation directly through zinc deficiency. Low zinc levels, affecting 30-50% of alcohol dependent persons, are associated w ith reduced immune function and HIV disease progression. Among HIV-infected people, high levels of microbial translocation (as measured by soluble CD14) and inflammation/altered coagulation (as measured by D- dimer) are each associated with an increased risk of death. Of importance, among HIV-infected persons, heavy drinking is also significantly associated with higher levels of D-dimer in cross-sectional studies. Of note, initiation of antiretroviral therapy (ART) is associated with a reduction in D-dimer levels. Yet the following is not known: is there a longitudinal relationship between alcohol consumption and these biomarkers independent of ART;and does zinc supplementation improve biomarker levels? Answering these questions requires a setting with prevalent HIV infection, heavy alcohol use and limited current ART use. As Russia has a relatively young, expanding HIV epidemic, a growing HIV treatment infrastructure and enormous per capita alcohol consumption, St. Petersburg is a setting where this research is possibi e. Thus, as part of the Uganda, Russia, Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium, we seek to create the Russia ARCH cohort from participants of a recently completed NIAAA-funded randomized controlled trial (RCT) of HIV-infected Russian heavy drinkers and perform the following: [1] an assessment of the longitudinal association between alcohol consumption and biomarkers of microbial translocation (sCD14) and inflammation/altered coagulation (D-dimer);[2] implementation of the Zinc Intervention Nested in a Cohort (ZINC) study, a double-blinded, placebo controlled, RCT to determine if short term zinc supplementation results in lower biomarker levels and whether the effects differ based on alcohol consum ption. These studies will clarify the association between alcohol and key biomarkers overtime and evaluate a pragmatic treatment, zinc supplementation, as a therapy in HIV-infected heavy drinkers.
The Russia ARCH Cohort and the ZINC study will draw from an established cohort of HIV-infected heavy drinkers to examine alcohol's impact on biomarkers reflecting microbial translocation and inflammation/ altered coagulation and to evaluate a pragmatic treatment: zinc supplementation. With successful completion of the specific aims, the study can clarify the association between alcohol and these biomarkers overtime and assess if zinc merits consideration in larger studies as a therapy in HIV-infected heavy drinkers.
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