Trial of Vitamin D in HIV Progression

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of vitamin D3 (cholecalciferol) supplementation on HIV progression and incidence of pulmonary tuberculosis among HIV-positive Tanzanian adult men and women initiating highly active antiretroviral therapy (HAART).

Detailed Description
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HIV-infected adults initiating antiretroviral therapy in resource-limited settings experience high mortality, pulmonary tuberculosis, and other comorbidity rates during the first year of HIV treatment. Observational studies have shown low vitamin D is a risk factor for HIV progression and incidence of pulmonary tuberculosis among adults initiating HAART; however, whether this relationship is causal and if vitamin D supplementation starting at HAART initiation can improve health outcomes has not been determined. This study is a randomized, double-blind, placebo-controlled trial conducted to examine the effect of vitamin D3 supplementation on morality and pulmonary tuberculosis for adults initiating HAART. Participants are HIV-positive Tanzanian men and women aged 18 years and older, who are initiating HAART at the time of randomization whose baseline 25-hydroxyvitamin D (25(OH)D) concentration is <30ng/mL. Eligible individuals are randomized to receive a) a vitamin D3 regimen consisting 50,000 IU of vitamin D3 taken orally once per week for 4 weeks (weeks 0, 1, 2, 3) followed by 2,000 IU of vitamin D3 supplements taken orally once per day starting at 4 weeks until study discharge at 12 months or b) placebo pills taken once weekly for 4 weeks (weeks 0, 1, 2, 3) followed by placebo pills taken daily starting at 4 weeks until study discharge. Participants will be followed for 12 months after ART initiation.

Official Title
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Trial of Vitamin D in HIV Progression

Conditions
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HIV Infection

Intervention / Treatment
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* Dietary Supplement: Vitamin D3 (cholecalciferol)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-positive Men or Women 18 Years of Age or older Initiating HAART at time of randomization 25(OH)D concentration <30 ng/mL at HAART initiation Exclusion Criteria: Pregnant Women Enrolled in another micronutrient trial

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3 (cholecalciferol)<br> | Dietary Supplement: Vitamin D3 (cholecalciferol)<br>* Supplements containing 50,000 IU of vitamin D3 (cholecalciferol) taken orally once per week for 4 weeks (weeks 0, 1, 2, 3) followed by 2,000 IU of vitamin D3 (cholecalciferol) supplements taken orally once per day starting at 4 weeks until study discharge at 12 months<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo pills taken once weekly for 4 weeks (weeks 0, 1, 2, 3) followed by placebo pills taken orally once per day starting at 4 weeks until study discharge at 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause death |  | within 12 months after randomization | 
| Pulmonary tuberculosis |  | within 12 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4+ T-cell count |  | 6 and 12 months after randomization | 
| Physician diagnosis of comorbidities |  | within 12 months after randomization | 
| Parathyroid hormone (PTH) |  | 1, 6, and 12 months after randomization | 
| Alkaline phosphatase (ALP) |  | 1, 6, and 12 months after randomization | 
| >10% weight loss |  | monthly from month 1 to month 12 | 
| Wasting (BMI <18.5 kg/m2) |  | monthly from month 1 to month 12 | 
| Hypercalcemia |  | 1, 6, and 12 months after randomization | 
| Physical activity |  | 6 and 12 months after randomization | 
| Immunologic biomarker levels (IL-2, IL-12, IFN-γ, and cathelicidin) |  | 1, 6, and 12 months after randomization | 
| Depression and anxiety scores |  | 6 and 12 months after randomization |