Zinc for HIV Disease Among Alcohol Users - an RCT in the Russia ARCH Cohort
Condition: HIV Infection; Alcohol Use
MeSH terms: Alcohol Drinking
Study type: Interventional

Summary: 
      This study is a double-blinded randomized controlled trial (RCT) to assess the efficacy of
      zinc supplementation vs. placebo among 250 HIV-infected Russians from the Russia ARCH Cohort,
      who are ART-naive at enrollment and have a recent history of heavy drinking.
    

Detailed description: 
      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-infected 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-infected 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.
    

Intervention name(s): Zinc gluconate; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Study participants will be randomly assigned to a zinc gluconate or placebo group and will be instructed to take one pill of study medication orally daily for 18 months.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Alcohol Use; Microbial Translocation; Inflammation; Altered Coagulation; Russia; Zinc; AMI; VACS index; Reynolds risk score