Zinc supplements: a safe, cheap and effective way of preventing dangerous CD4 cell loss in patients with HIV?

Zinc supplementation significantly reduces the risk of CD4 cell counts falling below the critical 200 cells/mm³ level, US investigators report in the June 15^th edition of Clinical Infectious Diseases.

Daily doses of zinc also reduced reported diarrhoea.

“Nutritional levels of zinc supplementation given to HIV-infected adults resulted in a 4-fold decrease in the likelihood of immunological failure”, comment the investigators.

Adequate zinc levels are essential for good immune function. However, research has shown that as many as 50% of HIV-positive patients have deficient levels of zinc, and this has been associated with faster HIV disease progression and an increased risk of death.

Supplementation with zinc has been shown to delay HIV disease progression.

The risk of potentially life-threatening opportunistic infections is high for HIV-positive patients when their CD4 cell count falls below 200 cells/mm³. When a patient’s CD4 cell count falls below this threshold, they are defined as having experienced immunological failure, as are individuals whose CD4 cell count does not increase after starting HIV treatment.

Investigators in the US wished to see if daily supplementation with zinc helped to reduce the risk of immunological failure, illness, and death in a cohort of 231 HIV-positive patients in the United States.

These individuals were equally randomised to take a daily dose of zinc (15mg men, 12mg women) or a placebo. The study lasted 18 months, and the patients were monitored at regular intervals.

The mean age of the study participants was 43 years, 77% were black and 73% were men.

Antiretroviral therapy was being taken by 62% of patients, but only 29% of these individuals had an undetectable viral load.

At the end of the study, the patients who received supplementation had significantly higher zinc levels than those who were randomised to receive the placebo (p = 0.047).

Zinc supplementation was safe, and there were no serious side-effects were reported.

There was no evidence that zinc supplements lowered viral load. Similar proportions of patients taking antiretroviral therapy in both arms of the study had a detectable viral load.

However, the investigators found that zinc supplementation reduced the risk of immunological failure by approximately 75% (RR = 0.24; 95% CI, 0.10-0.56, p = 0.002).

On entry to the study, a third of patients reported a history of diarrhoea within the last twelve months, and 12% said that this had been severe. Zinc supplementation reduced the risk of diarrhoea by 60% (p = 0.19), and the investigators found a significant link between low zinc levels and reporting diarrhoea (p < 0.001).

There was no evidence that taking zinc supplements reduced the risk of death. A total of eleven patients in the treatment arm died compared to eight in the placebo arm.

A subgroup analysis was performed that was restricted to the patients taking antiretroviral therapy who had an undetectable viral load. In total, four patients experienced immunological failure, and all were taking the placebo.

The investigators suggest that zinc supplementation prevented immunologic failure by improving thymic function.

They conclude, “this evidence supports the recommendation of zinc therapy as a safe, simple, and cost-effective tool to improve the immune response and to reduce morbidity and should be considered as an adjunct therapy for HIV infection.”