title: Randomized, controlled clinical trial of zinc supplementation to prevent immunological failure in HIV-infected adults.
abstract: BACKGROUND
  Adequate zinc is critical for immune function; however, zinc deficiency occurs in >50% of human immunodeficiency virus (HIV)-infected adults. We examined the safety and efficacy of long-term zinc supplementation in relation to HIV disease progression.
  
  
  METHODS
  A prospective, randomized, controlled clinical trial was conducted involving 231 HIV-infected adults with low plasma zinc levels (<0.75 mg/L), who were randomly assigned to receive zinc (12 mg of elemental zinc for women and 15 mg for men) or placebo for 18 months. The primary end point was immunological failure. HIV viral load and CD4(+) cell count were determined every 6 months. Questionnaires, pill counts, and plasma zinc and C-reactive protein levels were used to monitor adherence to study supplements and antiretroviral therapy. Intent-to-treat analysis used multiple-event analysis, treating CD4(+) cell count <200 cells/mm(3) as a recurrent immunological failure event. Cox proportional hazard models and the general-linear model were used to analyze morbidity and mortality data.
  
  
  RESULTS
  Zinc supplementation for 18 months reduced 4-fold the likelihood of immunological failure, controlling for age, sex, food insecurity, baseline CD4(+) cell count, viral load, and antiretroviral therapy (relative rate, 0.24; 95% confidence interval, 0.10-0.56; P<.002). Viral load indicated poor control with antiretroviral therapy but was not affected by zinc supplementation. Zinc supplementation also reduced the rate of diarrhea by more than half (odds ratio, 0.4; 95% confidence interval, 0.183-0.981; P=.019), compared with placebo. There was no significant difference in mortality between the 2 groups.
  
  
  CONCLUSIONS
  This study demonstrated that long-term (18-month) zinc supplementation at nutritional levels delayed immunological failure and decreased diarrhea over time. This evidence supports the use of zinc supplementation as an adjunct therapy for HIV-infected adult cohorts with poor viral control. Trial registration. ClinicalTrials.gov identifier: NCT00149552.
authors.affiliation: Florida International University, R. Stempel College of Public Health and Social Work, Miami, Florida, USA. baumm@fiu.edu
authors.forename: Marianna K
authors.initials: MK
authors.lastname: Baum
authors.forename: Shenghan
authors.initials: S
authors.lastname: Lai
authors.forename: Sabrina
authors.initials: S
authors.lastname: Sales
authors.forename: J Bryan
authors.initials: JB
authors.lastname: Page
authors.forename: Adriana
authors.initials: A
authors.lastname: Campa
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D019587:Dietary Supplements; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007154:Immune System Diseases / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load; D015032:Zinc / Q000172:deficiency / Q000627:therapeutic use*
chemical_list: D015032:Zinc
references.citation: J Nutr. 2000 May;130(5S Suppl):1421S-3S
references.pmid: 10801954
references.citation: JAMA. 1988 May 20;259(19):2850-1
references.pmid: 3367449
references.citation: Clin Infect Dis. 2005 Aug 1;41(3):361-72
references.pmid: 16007534
references.citation: Clin Infect Dis. 2003;37 Suppl 2:S117-23
references.pmid: 12942385
references.citation: Lancet. 2005 Nov 26;366(9500):1862-7
references.pmid: 16310552
references.citation: J Acquir Immune Defic Syndr (1988). 1991;4(10):976-80
references.pmid: 1890606
references.citation: Curr Opin Pulm Med. 2004 May;10(3):176-82
references.pmid: 15071368
references.citation: J Med Virol. 2005 Jun;76(2):153-60
references.pmid: 15834865
references.citation: Curr HIV Res. 2008 Mar;6(2):100-7
references.pmid: 18336257
references.citation: J Infect Dis. 1997 Feb;175(2):247-54
references.pmid: 9203644
references.citation: AIDS. 1992 Jul;6(7):701-8
references.pmid: 1503689
references.citation: Biometrics. 1986 Mar;42(1):121-30
references.pmid: 3719049
references.citation: Clin Infect Dis. 2009 Feb 1;48(3):328-37
references.pmid: 19123868
references.citation: Pediatr Int. 2003 Oct;45(5):555-9
references.pmid: 14521531
references.citation: AIDS. 1995 Sep;9(9):1051-6
references.pmid: 8527077
references.citation: MMWR Recomm Rep. 2008 Dec 5;57(RR-10):1-12
references.pmid: 19052530
references.citation: Ann N Y Acad Sci. 1992 Apr 15;650:94-8
references.pmid: 1605503
references.citation: Am J Clin Nutr. 1997 Aug;66(2):460S-463S
references.pmid: 9250133
references.citation: Food Nutr Bull. 2007 Sep;28(3 Suppl):S403-29
references.pmid: 17988005
references.citation: AIDS Rev. 2006 Apr-Jun;8(2):88-97
references.pmid: 16848276
references.citation: Int J STD AIDS. 2008 Jun;19(6):410-3
references.pmid: 18595880
references.citation: Ann Intern Med. 2000 Sep 19;133(6):401-10
references.pmid: 10975957
references.citation: Am J Epidemiol. 1993 Dec 1;138(11):937-51
references.pmid: 7903021
references.citation: J Acquir Immune Defic Syndr. 2006 Oct 1;43(2):197-201
references.pmid: 16940855
references.citation: Int J Immunopharmacol. 1995 Sep;17(9):719-27
references.pmid: 8582783
references.citation: J Acquir Immune Defic Syndr. 2006 Dec 1;43(4):475-82
references.pmid: 17019373
references.citation: N Engl J Med. 1995 Sep 28;333(13):839-44
references.pmid: 7651474
references.citation: Br J Nutr. 1993 Jan;69(1):243-55
references.pmid: 8457531
references.citation: Int Arch Allergy Immunol. 1993;101(2):126-31
references.pmid: 8508050
references.citation: J Pediatr. 1999 Aug;135(2 Pt 1):208-17
references.pmid: 10431116
references.citation: Postgrad Med J. 1990 Dec;66(782):1025-8
references.pmid: 2128123
references.citation: J Acquir Immune Defic Syndr. 2008 Aug 15;48(5):541-6
references.pmid: 18645520
references.citation: J Infect Dis. 1996 Jul;174(1):191-4
references.pmid: 8655993
references.citation: Stat Methods Med Res. 2007 Apr;16(2):103-22
references.pmid: 17484295
references.citation: J Acquir Immune Defic Syndr. 2005 Nov 1;40(3):288-93
references.pmid: 16249702
references.citation: J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Dec 1;16(4):272-8
references.pmid: 9402074
references.citation: AIDS. 2007 Jan 2;21(1):108-10
references.pmid: 17148977
references.citation: Br J Nutr. 2006 Apr;95(4):762-70
references.pmid: 16571156