Zn Supplementation in HIV Immunological Non Responders

NCT06612554 | Recruiting

• 2 other identifiers: 2023/11335/IPI23/00456
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Zinc is an essential micronutrient crucial for the normal functioning of the human immune system. Zinc deficiency impairs immune function and increases infection risk, especially in vulnerable populations like people living with HIV. This project aims to study the role of zinc supplementation in improving immune response in HIV-infected individuals who are Immunological Non-Responders (INRs)-people who have not restored Cluster of differentiation 4 (CD4) T-cell counts despite receiving antiretroviral therapy (ART). INRs face a higher risk of opportunistic infections, non-HIV comorbidities due to high inflammation, and generally have a poorer prognosis. Zinc supports immune function by aiding in immune cell development, cytokine production, and maintaining mucosal barrier integrity. Several studies have investigated zinc supplementation in HIV-infected individuals, showing significant increases in CD4 counts and a reduction in opportunistic infections. However, the doses used vary, and the results are sometimes contradictory. Our objective is to study whether zinc supplementation in INRs improves immune function, specifically by increasing CD4 counts, decreasing inflammation, and affecting other immune parameters. This project involves a clinical trial where INRs will be randomly assigned to receive 75mg of elemental zinc daily (in the form of 3 zinc acetate tablets) along with their usual treatment or to continue their treatment without zinc supplements. We will assess whether zinc supplementation increases CD4 lymphocytes, reduces inflammation in INRs, and induces immune system changes. We will also investigate immune system functionality by measuring the presence of the Torque Teno Virus (TTV), a harmless virus, and see how zinc supplementation impacts its control by monitoring viral load changes. Recent research by our group has demonstrated that zinc has both antiviral and anti-inflammatory effects. Zinc supplementation is generally safe and well-tolerated, with few adverse effects. Zinc is available in various forms, including gluconate, acetate, and sulfate. Although the recommended daily dose is 40mg, studies have shown that doses exceeding 80mg have been safely administered for over 10 years without side effects. We have selected a 75mg daily dose of elemental zinc for several reasons. Studies that showed no effect used lower doses (15-20mg/day), and our research found that 75mg/day improved outcomes in acute viral infections like Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2). We believe previous failures to show zinc's efficacy were due to insufficient dosing. After extensive literature review, we concluded that 75mg daily is safe and likely to produce the desired effects. Our goal is to demonstrate the efficacy of zinc as an immunomodulatory agent. If successful, this could be a simple and cost-effective way to improve the quality of life for many people. We would recommend its widespread use under medical supervision, particularly at the doses being studied.

Conditions

HIV; Zinc Status; HIV Infection

Keywords

Zinc Supplementation; HIV Immunological Non-Responder; Immune response; immune activation; Inflammation

Outcome Measures

Primary Outcomes (1)

• CD4+ T-cell number change

  CD4+ T-cell count (cells/ml)

  16 weeks

Secondary Outcomes (10)

• Change in CD4+Tcell activation

  16 weeks

• Change in CD8+Tcell activation

  16 weeks

• Change in Quality of Life EuroQol-5D-3L

  16 weeks

• Changes in Interleukin-6

  16 weeks

• Changes in C-Reactive protein

  16 weeks

Other Outcomes (8)

• Changes at week 24 CD4+ T-cell number change

  Week 24

• Changes at week 24 CD4+Tcell activation

  Week 24

• Changes at week 24 CD8+Tcell activation

  Week 24

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo tablets will be administered. Three Tablets will be with the same shape and size that Zn supplement tablets during 16 weeks

Other: Placebo

Zn Supplementation

EXPERIMENTAL

16 weeks with 3 tablets of zinc (83mg Zinc acetate/tablet)

Dietary Supplement: zinc acetate

Interventions

zinc acetate DIETARY_SUPPLEMENT

Participants in Control group. They will continue the SoC + 3 tablets of placebo and participants in Zinc supplementation group. Tablets will be separated 12h (just in case the ART is based in Integrase Inhibitors (INSTI)) during supplementation for 16 weeks with 3 tablets of zinc (83mg Zinc acetate/tablet).

Zn Supplementation

Placebo OTHER

participants in Control group. They will continue the SoC + 3 tablets of placebo. 3 tablets separated 12h from ART during 16 weeks

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• confirmed HIV infection;
• years or older
• Serum zinc levels less than 150ug/dl (normal range considered 75-150 ug/dl)
• HIV-1 infection on stable ART for at least 3 months with cumulative ART duration of at least 6 months
• Undetectable (less than 50copies/ml) persistently (isolated transient increases in viremia of less than 1000 copies/ml will be accepted)
• Persistent less than 500CD4+ T-cells/mm3 at enrolment or an increase of less than 80 cells/mm3 after one year of viral undetectability

You may not qualify if:

• Pregnancy
• Lactation
• Active infectious or inflammatory condition
• Uncontrolled diabetes
• Serum Zinc levels more than 150ug/dl

Sponsors & Collaborators

• Parc de Salut Mar: lead
• Hospital de Sabadell: collaborator

Study Sites (1)

Hospital del Mar

Barcelona, 08003, Spain

RECRUITING

MeSH Terms

Conditions

HIV Infections; Inflammation

Interventions

Zinc Acetate

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetic Acid; Acetates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Central Study Contacts

Robert C Güerri-Fernández, M.D. Ph.D.

CONTACT

+34 932483246; rguerri@hmar.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2024
• First Posted: September 25, 2024
• Study Start: January 2, 2025
• Primary Completion: June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 16, 2026

Record last verified: 2025-07

Locations

ES (1)