Vitamin D Dose Finding Study

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.