Zinc Supplements Delay CD4 Cell Loss and Reduce Diarrhea in People with HIV

		SUMMARY: HIV positive people who received zinc supplements in a randomized clinical trial were about 75% less likely to see their CD4 cell count drop below 200 cells/mm3 or fail to recover adequately after starting antiretroviral therapy, according to a study published in the June 15, 2010 issue of Clinical Infectious Diseases. Zinc recipients were also half as likely to have diarrhea. These findings are important, as research indicates that more than 50% of adults with HIV may have zinc deficiency.

By Liz Highleyman

Marianna Baum from Florida International University in Miami and colleagues examined the safety and efficacy of long-term zinc supplementation and its relation to HIV disease progression. Adequate zinc is critical for proper immune function, they noted as background, but zinc deficiency occurs in more than half of HIV positive adults.

This prospective clinical trial included 231 HIV positive adult participants with low plasma zinc levels (< 0.75 mg/L). They were randomly assigned to receive zinc supplements (12 mg of elemental zinc for women and 15 mg for men) or placebo for 18 months.

Most participants (73%) were men, 77% were black, and the average age was 43 years. About two-thirds were on combination antiretroviral therapy (ART), but 69% nevertheless had detectable viral load; at study entry one-third had a CD4 cell count below 200 cells/mm3, the danger zone for opportunistic infections.

HIV viral load and CD4 cell count were measured every 6 months. Questionnaires, pill counts, and levels of plasma zinc and C-reactive protein (a marker of inflammation) were used to monitor adherence to supplements and ART. Immunological failure was defined as a CD4 count < 200 cells/mm3.

Results

	Zinc supplementation for 18 months reduced the likelihood of immunological failure by 4-fold versus placebo, after controlling for age, sex, food insecurity, baseline CD4 count, viral load, and ART (relative rate 0.24, or 76% reduction; P < 0.002).
	In a sub-analysis of participants who had undetectable viral load on ART, the 4 patients who experienced immunological failure were all in the placebo group.
	Overall, participants achieved poor virological control despite ART, but viral load was not affected by zinc supplementation.
	Zinc supplementation reduced the frequency of diarrhea by 60% compared with placebo (odds ratio 0.4; P = 0.019).
	However, there was no significant difference in mortality between the zinc and placebo groups.

"This study demonstrated that long-term (18-month) zinc supplementation at nutritional levels delayed immunological failure and decreased diarrhea over time," the investigators concluded. "This evidence supports the use of zinc supplementation as an adjunct therapy for HIV-infected adult cohorts with poor viral control."

In an accompanying editorial, Saurabh Mehta and Wafaie Fawzi from Harvard School of Public Health described some of the biological mechanisms by which zinc deficiency might be associated with disease progression, including suppression of cell-mediated immunity, decreased levels of a thymus hormone that stimulates T-cell differentiation, impaired regeneration of CD4 cells, altered cytokine levels, and increased inflammation in the gut.

Florida International University, R. Stempel College of Public Health and Social Work, Miami, FL; University of Miami, Miller School of Medicine, Miami, FL; Johns Hopkins University, Baltimore, MD.

6/11/10

References

MK Baum, S Lai, S Sales, and others. Randomized, controlled clinical trial of zinc supplementation to prevent immunological failure in HIV-infected adults. Clinical Infectious Diseases 50(12): 1653-1660 (Abstract). June 15, 2010.

S Mehta and W Fawzi. Micronutrient supplementation as adjunct treatment for HIV-infected patients (Editorial). Clinical Infectious Diseases 50(12): 1661-1663. June 15, 2010.