Vitamin D Supplements for HIV-positive Patients on cART

In the post-HAART era, patients continue to suffer from the adverse medical consequences of
HIV/AIDS. The adverse effects include incomplete immune reconstitution, chronic
inflammation, depression, increased risk of cardiovascular and metabolic disease, and low
bone density. Clinical trials suggest that vitamin D supplements can increase bone density,
reduce inflammation, alleviate depression, and increase longevity if given in adequate
doses. To achieve maximum benefits, most vitamin D experts in the HIV field agree that
vitamin D treatments should raise the concentration of 25-hydroxyvitamin D [25(OH)D] above
30 ng/ml. A growing number of HIV care providers desire an evidence-based protocol for
achieving these 25(OH)D target levels. This project addresses the need for a validated
protocol for treating vitamin D deficiency in HIV-positive individuals on HAART. The goal of
Aim I is to conduct a 12-mo randomized, double-blinded trial comparing two dosing regimens
of oral vitamin D plus 0.5 g/d of calcium in patients on stable HAART who have 25(OH)D
levels ≤ 25 ng/ml and undetectable HIV viral load at baseline (100 per arm). Medication
event monitoring system (MEMS) caps will be used to record supplement use and to promote
adherence. Subjects in Protocol A will receive 50,000 IU/wk of vitamin D2 for 8 wk followed
by 1000 IU/d of vitamin D3 for 48 wk. Subjects in Protocol B will receive 2000-4000 IU/d of
vitamin D3, depending on the basal 25(OH)D level, with dose titration, as necessary, based
on the slope of the initial response. The primary outcome measure is the difference in the
percentage of subjects with 25(OH)D levels in the range of 30-60 ng/ml at 12 mo. The
secondary outcome is the slope of the 25(OH)D response curve during various time intervals.
The goal of Aim II is to compare the impact of the two protocols on markers of disease. The
primary outcome measure is the change in the CD4+T cell count. Secondary outcomes include
changes in CD4+ T cell subsets, markers of inflammation, markers of bone and calcium
metabolism, self-reported psychological status, viral load, side effects, safety, and
adherence. To our knowledge, this trial is the first head-to-head comparison of a regimen
that uses a loading dose of vitamin D2 with a regimen that uses a tiered starting dose of
vitamin D3. The project will yield a validated protocol for treating vitamin D deficiency in
HIV-infected patients on HAART and will provide initial data about the risks and health
benefits of vitamin D and calcium supplements. This information is essential for designing
definitive multicenter trials in the future.

Inclusion Criteria:

- age, 18-70 yr

- HIV-infected

- on a stable HAART regimen for at least 12 mo with an undetectable HIV viral load for
6-mo

- willing to participate

- not receiving vitamin D supplementation in a form other than vitamin D2 or vitamin D3

- not receiving treatment for bone disease

- not receiving medications known to alter bone mineralization

- not suffering from conditions known to affect vitamin D, calcium, and/or phosphate
levels (including clinically significant hypocalcemia, primary hyperparathyroidism)

- not experiencing kidney disease based on GFR > 60 min/ml/1.73 m2, 10) 25(OH)D level <
25 ng/ml

- not meeting criteria of the National Osteoporosis Foundation for established bone
disease (osteoporosis, osteomalacia) requiring immediate treatment

- not consuming more than 2.0 gm of calcium/day in food and supplements combined
outside the trial

- not consuming more than 800IU/day of vitamin D outside the trial

- not suffering from an unstable medical condition likely to preclude participation in
a 12 month trial

- able to ingest and absorb food and nutrients

- not pregnant or planning to become pregnant.

Exclusion Criteria:

- No history or evidence of HIV infection

- HIV viral load positive

- outside the age range