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 HIV-infected adults. We examined the safety and efficacy of long-term zinc supplementation on HIV disease progression. Methods A prospective randomized controlled clinical trial was conducted with 231 HIV+ adults with low plasma zinc levels (<0.75 μg/ml), randomly assigned into zinc (12 mg of elemental zinc for women and 15 mg for men) or placebo, for 18 months. The primary endpoint was immunological failure. HIV-viral load and CD4+ cell count were determined every 6 months. Questionnaires, pill-counts, plasma zinc and C-reactive protein (hsCRP) were used to monitor adherence with study supplements and ART. Intent-to-treat analysis utilized multiple-event analysis, treating CD4+ cell count <200 cells/mm3 as 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 four-fold the likelihood of immunological failure, controlling for age, gender, lack of food, baseline CD4+ cell count, viral load, and antiretroviral therapy (RR=0.24[95%CI:0.10,0.56],p<0.002). Viral load indicated poor control with ART but was not affected by zinc supplementation. Zinc supplementation also reduced the rate of diarrhea by more than half (OR=0.4[95%CI:0.183-0.981],p=0.019) compared to placebo. There was no significant difference in mortality between the two groups. Conclusion 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 in HIV+ adult cohorts with poor viral control. Summary 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 in HIV+ adult cohorts with poor viral control.

Effect of zinc on immune recovery in HIV patients. Medellín 2013. Randomized controlled trial

“…terms of development and productivity, generating physically challenged adults with low levels of productivity (22).…”

Zinc Status in Virological Controlled Human Immunodeficiency Virus Type 1 Infected Patients

“…However, in these studies the percentage of patients with virological control and the absence of other confounding factors is low [3,9].…”

Review of randomized controlled trials of nutritional supplementation in people living with HIV

“…29,33,34,[53][54][55] Although a Cochrane review 56 found no definite evidence of the role of nutritional supplementation on morbidity, mortality, and HIV disease progression among PLWH, and vitamin A supplementation seems to be beneficial only in children, subsequent reports from RCTs of supplementation have found benefits for both adults and children. [23][24][25]39,[57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72] ART and nutritional supplementation are not in contradiction, as concluded by another review, 73 as each of them support the recovery of the immune system by different mechanisms.…”

“…10 In the era of ART, wasting is more frequently observed in cases with virologic and/or immunological failure, who are living in poor socioeconomic conditions and with high food insecurity. 10,39 Micronutrient deficiencies have also been observed, even in patients receiving chronic ART. Jones et al 40 reported a high prevalence of zinc deficiency in participants on ART, adjusting for parameters of acute-phase reaction.…”