The combination of heavy alcohol consumption and HIV infection is associated with increased mortality, HIV disease progression, acute myocardial infarction (AMI) and a proinflammatory state characterized by increased biomarker levels of inflammation. Heavy alcohol use and HIV infection are both causes of microbial translocation, the process by which bacterial products from the gastrointestinal (GI) tract leak across the GI membrane to the portal circulation. Microbial translocation causes immune activation leading to end organ damage. Alcohol can cause microbial translocation via zinc deficiency. Zinc deficiency is common among HIV+ heavy drinkers and linked to high mortality rates. Zinc supplementation is affordable, available, does not interfere with ART, and has minimal adverse drug reactions. In animal models zinc reduces ethanol associated microbial translocation. In human studies zinc slows HIV disease progression and reduces levels of inflammatory biomarkers which are strongly linked to mortality. Given zinc's potential efficacy we propose to conduct Zinc for INflammation and Chronic disease in HIV (ZINC HIV), a double-blinded randomized controlled trial to assess the efficacy of zinc supplementation vs. placebo among 250 HIV+ Russians, who are ART-naive at enrollment and have a recent history of heavy drinking. We will recruit most of our participants from the Russia cohort within the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium study.
Our specific aims will test the efficacy of zinc supplementation, compared to placebo to (1) improve markers of mortality as measured by the VACS index;(2) slow HIV disease progression as measured by CD4 cell count;(3) improve markers of AMI risk as measured by the Reynolds risk score;and (4) lower levels of microbial translocation and inflammation as measured by serum biomarkers. We hypothesize that as compared with placebo, patients receiving zinc supplementation will have significantly lower AMI and mortality risk as measured by the VACS index and Reynolds risk scores;higher CD4 cell counts;lower levels of biomarkers for microbial translocation and inflammation. Importantly, if our hypotheses are true, zinc supplementation could ultimately become a standard adjunctive therapy complementing alcohol interventions among HIV+ persons even in resource limited environments.

Public Health Relevance

The combination of heavy alcohol consumption and HIV infection results in serious health problems and an increased risk of death. Although it is not exactly clear how alcohol and HIV do this, inflammation appears to play an important role. Zinc supplementation has anti-inflammatory properties. This study is designed to see if giving zinc supplementation to HIV infected people who are heavy drinkers reduces the risk of serious health problems and death.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA021989-02
Application #
8549930
Study Section
Special Emphasis Panel (ZAA1-DD (09))
Program Officer
Wang, Joe
Project Start
2012-09-25
Project End
2017-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$545,241
Indirect Cost
$48,737
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118
Forman, Leah S; Patts, Gregory J; Coleman, Sharon M et al. (2017) Use of an android phone application for automated text messages in international settings: A case study in an HIV clinical trial in St. Petersburg, Russia. Clin Trials :1740774517726067
Asiimwe, Stephen B; Fatch, Robin; Patts, Gregory et al. (2017) Alcohol Types and HIV Disease Progression Among HIV-Infected Drinkers Not Yet on Antiretroviral Therapy in Russia and Uganda. AIDS Behav 21:204-215
Edelman, E Jennifer; Lunze, Karsten; Cheng, Debbie M et al. (2017) HIV Stigma and Substance Use Among HIV-Positive Russians with Risky Drinking. AIDS Behav 21:2618-2627
Idrisov, Bulat; Lunze, Karsten; Cheng, Debbie M et al. (2017) Food Insecurity, HIV Disease Progression and Access to Care Among HIV-Infected Russians not on ART. AIDS Behav 21:3486-3495
Tsui, Judith I; Cheng, Debbie M; Coleman, Sharon M et al. (2017) Pain and Risk Behaviors Among HIV-Infected Persons in St. Petersburg, Russia. AIDS Behav 21:1775-1781
Idrisov, Bulat; Lunze, Karsten; Cheng, Debbie M et al. (2017) Role of substance use in HIV care cascade outcomes among people who inject drugs in Russia. Addict Sci Clin Pract 12:30
Patts, Gregory J; Cheng, Debbie M; Emenyonu, Nneka et al. (2017) Alcohol Use and Food Insecurity Among People Living with HIV in Mbarara, Uganda and St. Petersburg, Russia. AIDS Behav 21:724-733
Tsui, Judith I; Ko, Stephen C; Krupitsky, Evgeny et al. (2016) Insights on the Russian HCV Care Cascade: Minimal HCV Treatment for HIV/HCV Co-infected PWID in St. Petersburg. Hepatol Med Policy 1:
Cannon, Abigail R; Morris, Niya L; Hammer, Adam M et al. (2016) Alcohol and inflammatory responses: Highlights of the 2015 Alcohol and Immunology Research Interest Group (AIRIG) meeting. Alcohol 54:73-7
So-Armah, Kaku A; Edelman, E Jennifer; Cheng, Debbie M et al. (2016) Effects of Heavy Drinking on T-Cell Phenotypes Consistent with Immunosenescence in Untreated HIV Infection. Alcohol Clin Exp Res 40:1737-43

Showing the most recent 10 out of 11 publications