Vitamin D Dose Finding Study

• Safety as determined by serum calcium and 25D concentrations and efficacy to replete vit D status determined by achieving a minimum serum 25D concentration of 32 ng/mL. [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]
  

• Cathelicidin antimicrobial protein activity will be used as an indicator of immune response to vit D depletion and repletion. [ Time Frame: 16 months ] [ Designated as safety issue: No ]
  

Drug: Cholecalciferol (Vit D3)
To test two oral daily doses (4000 vs. 7000 IU) of cholecalciferol (D3) dietary supplement (capsules or liquid) over a 3-month period in 44 children, adolescents and adults with HIV/AIDS.
Other Names:
• Carlson D Drops: The D Drop Company
• Nutraceutical Life Sciences Vitamin D3 2000 IU capsules: Vitacost
• NOW Foods 5000 IU softgels: Now Health Group, Inc.

The key role of vitamin D (vit D) in maintaining optimal bone health has long been recognized, but its role in modulating the innate immune response and inflammatory reaction has only recently come under active investigation. As such, vit D is an increasingly frequently chosen and prescribed high dose dietary supplement,because it is thought to improve immune and inflammatory status in healthy people of all ages, and in those with chronic diseases including HIV/AIDS. Vit D also has calciotrophic functions essential for bone health, and poor vit D status contributes to the osteopenia/osteoporosis associated with antiretroviral therapy (ART). Vit D may improve insulin/glucose/lipid metabolism, blood pressure and risk of some cancers, all of which may complicate HIV/AIDS and its treatments. Poor vit D status is common in patients with HIV/AIDS of all ages and factors such as age, skin pigment, lactose intolerance and sun exposure alter the risks for vit D deficiency. In the multicenter U.S. REACH study of adolescents (72% African American), with and without HIV, showed that 87% had low serum 25D concentrations (<15 ng/mL), compared to 34% in a recent sample of healthy African American children from Philadelphia. Young African Americans are disproportionately affected by HIV infection in the US (~ 55% among persons with HIV aged 13 to 24 years are African American), and are also at high risk for vit D deficiency. Vit D therapy has great promise to improve major medical conditions and the quality of life for our patients with HIV/AIDS, yet the potential role of vit D in the treatment of HIV/AIDS has not been formally tested. Well-designed randomized trials are urgently needed to determine vit D supplementation safety and efficacy.

The investigators propose a two-phase study to establish safety and efficacy of high dose vit D supplementation in children and adults with HIV/AIDS. In Study Phase I, the safety and efficacy of two oral vit D3 doses (4000 and 7000 IU/d) are determined over 12 weeks in 44 subjects ages 5.0 to 24.9 y. The key safety measure is concurrently elevated serum calcium and 25D concentrations. Efficacy is evaluated by serum 25D concentration and cathelicidin (innate immune, antimicrobial protein) mRNA expression. Study Phase II is a 12 month, double blind, randomized, placebo controlled supplementation study (n=52). Key outcomes include safety and longterm 25D concentration within the goal range (32 to 160 ng/mL), improved cathelicidin mRNA expression, and measures of bone, muscle, inflammation, growth and body composition status, and HIV/AIDS disease severity. Based on the evidence and promise, vit D clearly deserves to be among the first nutrients evaluated in the National Center for Complimentary and Alternative Medicine (NCCAM) HIV research program.