Micronutrients and Antioxidants in HIV Infection

Study Overview
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Brief Summary
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Infection with human immunodeficiency virus (HIV) causes decline in immunity or the ability to fight infection and progresses to acquired immunodeficiency disease (AIDS). Anti-HIV drug treatment has improved the prognosis of persons with HIV infection, but is expensive and potentially toxic. Low micronutrient levels occur in the blood even in early stages of HIV infection and increase risk of a poorer prognosis, but the role of micronutrient and antioxidant supplements in medical management of HIV/AIDS is not well defined. The proposed clinical trial aims to assess if supplementation of untreated HIV-infected adults with a micronutrient and antioxidant preparation can delay decline in immunity or disease progression or start of anti-HIV drug treatment compared with supplementation with standard multivitamins. If the findings are positive, the study has implications for health and health care savings.

Detailed Description
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Background: Antiretroviral therapy (ART) has improved the prognosis of persons with human immunodeficiency virus (HIV) infection, but is expensive and potentially toxic. Micronutrient deficiencies occur even in early stages of HIV infection and increase risk of morbidity, disease progression to acquired immunodeficiency syndrome (AIDS) and mortality, but the role of micronutrient antioxidant supplements in medical management of HIV/AIDS is not clear. Objective: To determine if supplementation of untreated asymptomatic HIV-infected persons with a broad-spectrum micronutrient and antioxidant preparation will reduce the rate of decline of CD4 T lymphocyte count, or delay emergence of documented CDC-defined AIDS-defining illness, or start of ART compared to 100% recommended daily allowance (RDA) multivitamins and minerals, and is safe. Study design: A prospective, randomized, controlled, double blind clinical trial of supplementation of 218 untreated asymptomatic HIV-infected adults with a micronutrient and antioxidant preparation or identical appearing RDA multivitamins and minerals for two years, with quarterly follow up in clinic for assessment of time from baseline to CD4 count <350 mm3, or emergence of documented CDC-defined AIDS-defining illness, or start of ART. Participants and sample size: 218 participants from clinics in Ontario and other participating centres of the CIHR Canadian HIV Trials Network (CTN). Study duration: approximately five years, allowing for approximately three years for participant accrual and two years follow-up. Eligibility criteria: The main eligibility criteria are: • Asymptomatic HIV-infected adults at least 18 years of age • CD4+ cells ≥375 and ≤750 cells/mm3 • No previous ART (excluding less than seven days and perinatal transmission prophylaxis) Study intervention: Oral supplementation with a broad spectrum micronutrient and antioxidant preparation (n=109) or identical appearing RDA multivitamins and minerals (n=109). Primary outcome: Time from baseline to CD4+ cell count <350 cells/mm3 (confirmed by two measures at least one week apart), or emergence of documented CDC-defined AIDS-defining illness, or start of ART Secondary outcomes: • Non-AIDS related adverse events • Tolerance of and adherence to study medication • Time from baseline to CD4+ cell count <350 cells/mm3 (confirmed by two measures at least one week apart) • Time from baseline to emergence of documented CDC-defined AIDS-defining illness • Time from baseline to start of ART • Serial quarterly lymphocyte measures: absolute lymphocyte count (ALC), CD4+, CD8+, and CD3+ cell counts, CD4%, CD8%, CD4:CD8 • Serial quarterly HIV RNA plasma viral load • Serum chemistries: Glucose, BUN, creatinine, total protein, C-reactive protein, albumin, alkaline phosphatase, ALT, AST, total bilirubin • Serum micronutrient levels: Carotene (quarterly) and vitamin B12 (quarterly), folate (six monthly) and vitamin D (25-OHD, six monthly) • Quality of Life measures: MOS HIV, EuroQol, and Health Utilities Index (HUI) Statistical analysis: Analysis of the primary outcome by intention-to-treat will compare time from baseline to primary outcome. Interim analyses are planned once 100 participants are followed for one year.

Official Title
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A Randomized Control Clinical Trial Of Micronutrient & Antioxidant Supplementation in Persons With Untreated HIV Infection

Conditions
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HIV Infection

Intervention / Treatment
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* Dietary Supplement: Micronutrients and antioxidants
* Dietary Supplement: Multivitamins and minerals


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: be an asymptomatic HIV infected adult at least 18 years of age have CD4+ cells between 375 and 750 cells/mm3 have received no ART (excluding less than seven days and perinatal transmission prophylaxis) if a woman of child bearing potential, have a negative pregnancy test within two weeks prior to randomization and agree to practice barrier method of birth control during the study be willing and able to sign informed consent and to comply with the study protocol Exclusion Criteria: have HIV-2 infection alone have known allergy or intolerance to any study medication ingredient be pregnant have active treatment for an acute opportunistic infection or malignancy have ALT greater than 3 x normal range have known cirrhosis of the liver have serum creatinine less than 133 umol/L abuse alcohol and recreational drugs be taking micronutrient (except vitamin D*) or natural health product supplements within 30 days of randomization *Maximum 2000 IU daily (Health Canada Guidelines).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Treatment group (Group A): Will receive micronutrients and antioxidants. Control group (Group B): Will receive identical appearing RDA multivitamins and minerals
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: Broad spectrum micronutrients<br>The experimental treatment medications (micronutrients and antioxidants) will be taken as one packet (8 capsules) twice a day with meals. Because of the presence of calcium, iron and zinc in the study medication, any other medication must be taken at least two hours before or after taking it. Participants may initiate the intervention at half dose (one packet of 8 capsules once a day) and increase to full dose after one week. The intervention will last for two years. | Dietary Supplement: Micronutrients and antioxidants<br>* 8 capsules twice daily for two years<br>* Other names: K-PAX Ultra;|
| Active Comparator: B: Identical appearing multivitamins<br>The active comparator/control medications (identical appearing RDA multivitamins and minerals) will be taken as one packet (8 capsules) twice a day with meals. Because of the presence of calcium, iron and zinc in the study medication, any other medication must be taken at least two hours before or after taking it. Participants may initiate the intervention at half dose (one packet of 8 capsules once a day) and increase to full dose after one week. The intervention will last for two years. | Dietary Supplement: Multivitamins and minerals<br>* 8 capsules twice daily for two years<br>* Other names: Centrum-like multivitamins and minerals;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from baseline to CD4+ cell count <350 cells/mm3 (confirmed by two measures at least one week apart), or emergence of documented CDC-defined AIDS-defining illness, or start of ART |  | Quarterly | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-AIDS related adverse events |  | Quarterly | 
| Tolerance of and adherence to study medication |  | Quarterly | 
| Time from baseline to CD4+ cell count <350 cells/mm3 (confirmed by two measures at least one week apart) |  | Quarterly | 
| Time from baseline to emergence of documented CDC-defined AIDS-defining illness |  | Quarterly | 
| Time from baseline to start of ART |  | Quarterly | 
| Serial quarterly lymphocyte measures (ALC, CD4+, CD8+, and CD3+ cell counts, CD4%, CD8%, CD4:CD8) |  | Quarterly | 
| Serial quarterly HIV RNA plasma viral load |  | Quarterly | 
| Serum chemistries: Glucose, BUN, creatinine, total protein, albumin, alkaline phosphatase, ALT, AST, total bilirubin, |  | Quarterly | 
| Serum micronutrient levels: carotene (quarterly), vitamin B12 (quarterly), folate (six monthly) and vitamin D (25-OHD six monthly) |  | Quarterly or as specified | 
| Quality of Life measures |  | Quarterly | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infection, Micronutrients, Antioxidants