Adjunct Therapy of Zinc Supplementation Increases Immunological Response in HIV-Infected Patients: A Systematic Review and Meta-Analysis

Dwijo Anargha Sindhughosa1, I Ketut Agus Somia2, *, Ketut Tuti Parwati Merati2, Ketut Suryana3
1 Internal Medicine Residency Program, Udayana University/Sanglah General Hospital, Denpasar, Bali, Indonesia
2 Department of Internal Medicine, Tropical and Infectious Disease Division, Udayana University/Sanglah General Hospital, Denpasar, Bali, Indonesia
3 Department of Internal Medicine, Immunology Division, Udayana University/Sanglah General Hospital, Denpasar, Bali, Indonesia

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© 2022 Sindhughosa et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Internal Medicine, Tropical and Infectious Disease Division, Udayana University/Sanglah General Hospital, Denpasar, Bali, Indonesia E-mails:,



Malnutrition greatly accelerates the impairment of immune function among HIV-infected patients. Zinc deficiency is often found in people living with HIV/AIDS, affecting their immune function. Several studies have evaluated the effect of zinc in HIV-infected patients, including CD4+ T-cells. However, the results have varied. This review aimed to evaluate the effect of zinc supplementation in HIV patients, particularly its effect on CD4+ T-cells count.


Relevant publications were obtained from PubMed database, Google Scholar, COCHRANE, and Science Direct. The primary outcome was CD4+ T-cells count, while the secondary outcomes were viral load and zinc levels. Year of publication, type of study, population, doses of zinc given, duration of zinc administration, sample size, age, and baseline CD4+ T-cells counts were also obtained and reported. Quantitative data from the publications were analyzed using a fixed-effect model or a random-effect model.


We evaluated 13 full-text articles on zinc supplementation in HIV-infected patients, involving 802 subjects for the experiment group and 742 subjects for the control group. Overall, zinc supplementation, whether as zinc supplementation-only or prepared as multiple micronutrient or multivitamin preparation, increases CD4+ T-cells counts by 33.14 cells/mm3 (p =0.02; 95% CI: 6.09 to 60.19), irrespective of age. Subgroup analysis revealed CD4+ T-cells counts also increase in patients who receive zinc supplementation-only preparation by 33.56 cells/mm3 (p = 0.04; 95% CI: 1.5 to 65.63). Zinc supplementation increases serum zinc levels with pooled mean difference of 15.41 µg/dl (p < 0.05; 95% CI: 12.77 to 18.06). However, the viral load did not significantly decrease with zinc supplementation, with a pooled mean difference of -4.02 copies/ml (p =0.7; 95% CI: -24.78 to 16.75), based on the random-effect model.


Zinc supplementation in HIV-infected patients enhances immunological response, characterized by an increase in CD4+ T-cells counts. In addition, it increases zinc serum levels in HIV-infected patients, indicating the importance of zinc supplementation in this group of patients.

Keywords: Zinc supplementation, HIV-infected patients, CD4+ T-cells, Immunological response, Viral load, Peptides.