Low plasma zinc levels and immunological responses to zinc supplementation in HIV-infected patients with immunological discordance after antiretroviral therapy

Immunological discordance in HIV-infected patients is associated with a higher risk of mortality and disease progression. Zinc is an essential micronutrient for immune function. A two-phase pilot study including a cross-sectional study to determine plasma zinc levels and a prospective, randomized, placebo-controlled trial to determine immunological responses after zinc supplementation was conducted in HIV-infected patients with immunological discordance in a medical school hospital. Immunological discordance was defined in patients who received antiretroviral therapy, had HIV RNA < 40 copies/mL, and a CD4⁺ cell count < 200 cells/mm³ that increased <30% from baseline after receiving ART with undetectable HIV RNA for 12 months. Of 31 patients, 12 (39%) had low plasma zinc levels (<75 μg/dL). Five of 12 patients with low plasma zinc levels and 8 of 19 patients with normal plasma zinc levels were randomized to receive zinc supplementation. The median changes in plasma zinc levels after supplementation versus placebo in patients with low plasma zinc levels were 29 versus 4.5 μg/dL, respectively. The CD4⁺ cell count significantly increased (176 versus 250 cells/mm³, P = 0.042) after zinc supplementation in patients with low plasma zinc levels. Further large-scale studies to determine long-term benefits of zinc supplementation in patients with immunological discordance are required.