Randomized, controlled clinical trial of zinc supplementation to prevent immunological failure in HIV-infected adults.
What this study found
Zinc supplementation for 18 months meaningfully delayed immunological failure in HIV-infected adults with zinc deficiency. The relative rate for immunological failure was 0.24 (95% confidence interval, 0.10-0.56; P < .002), indicating about a four-fold lower likelihood versus placebo. Zinc also reduced diarrhea over time (odds ratio, 0.4; 95% confidence interval, 0.183-0.981; P = .019). Viral load was not affected, mortality did not differ significantly (11 deaths in the zinc group vs 8 in placebo), and no adverse effects were observed.
- Study & population
- Randomized, double-blind, placebo-controlled trial in HIV-infected adults with low plasma zinc levels.
- Intervention
- Oral elemental zinc was given for 18 months at 12 mg/day for women and 15 mg/day for men, compared with placebo.
- Key limitation
- The trial was modest in size and limited to HIV-infected adults with low zinc levels, which narrows generalizability.
View source
Open PDFOriginal 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.