Zinc supplements delayed immune failure, decreased diarrhea in adults with HIV

Nutritional doses of zinc delayed immunological failure and decreased diarrhea in adults with HIV — supporting the use of zinc as an adjunct therapy in those with poor viral control from this population, according to study findings.

More than half of adults with HIV lack sufficient zinc levels, according to the researchers from Miami and Baltimore. Zinc deficiencies are often associated with reduced T cells; decreased humoral and cell-mediated immunity; lymphopenia; thymic atrophy; and frequent infections, they noted.

The 18-month study included 231 adults with HIV who had plasma zinc levels less than 0.75 mg/L. The researchers randomly assigned patients to elemental zinc supplement (12 mg for women, 15 mg for men) or placebo.

At the end of the study, patients assigned to zinc were four times less likely to experience immunological failure, defined as any CD4+ cell count less than 200 cells/mm³ (P<.002), after controlling for sex, age, food insecurity, viral load, baseline CD4+ cell count and antiretroviral therapy. Zinc also lowered the frequency of diarrhea by more than 50% (P=.019). These benefits were reached despite persisting detectable viral load in the majority of the patients.

“The results of this study can be generalized primarily to [populations with HIV] with prevalent zinc deficiency, such as drug users, children, men who have sex with men and populations in developing countries, as well as those with poor viral control while receiving ART,” the researchers wrote.

The researchers theorized that the improved CD4+ cell counts seen in their patients might be due to increased levels of active zinc-bound thymulin, a thymic peptide that helps mature the thymocytes that create T cells. Thymulin only activates when it binds to zinc.

“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,” they concluded.

An emerging theme in basic science studies of zinc (Zn) physiology is that Zn can act in a drug-like manner rather than strictly as a micronutrient, an idea that has been reflected in recent editorials. If this is the case, then a short regime of Zn at, or slightly above, the recommended daily value may be better than prolonged, low-dose treatment for specific indications. However, early reports indicated that intakes of Zn above nutritional levels were associated with disease progression in adults with HIV.

Baum and colleagues now show that low-dose, prolonged Zn supplementation of adults with HIV resulted in a 4-fold decrease in the likelihood of immunological failure [defined as a decrease of CD4+ cell count to <200 cells/mm³]. They conducted a randomized, double-blind, placebo-controlled trial in Miami, providing Zn-supplements (12mg for women, 15mg for men), or placebo, daily for 18 months, and for the first time, show that Zn supplementation significantly reduces the morbidity associated with HIV-related diarrhea, compared with placebo, in adults. The results of this study can be generalized primarily to populations with HIV with prevalent Zn deficiency, such as drug users, children, men who have sex with men and populations in developing countries, as well as those with poor viral control while receiving HAART. This report supports the recommendations of WHO and UNICEF - that Zn therapy is 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.

– Angus Scrimgeour PhD
Military Nutrition Division USARIEM

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