Vitamin D HIV Study on Postmenopausal Women

The purpose of this study is to determine the effects of vitamin D repletion on rates of bone
loss and indices of immune function in HIV+ postmenopausal women. Lower baseline serum
Vitamin D levels, as assessed by measuring serum 25-hydroxyvitamin D (25-OHD) were associated
with a trend toward more bone loss. In addition, the investigators found that despite
providing supplements that contained approximately 600 IU vitamin D, serum 25-OHD did not
increase during the first year. Provision of adequate calcium and vitamin D is the
cornerstone of effective prevention and therapy of osteoporosis. HIV-infected patients may be
at increased risk of having vitamin D deficiency because they take several medications that
may interfere with vitamin D action. Therefore, the investigators will recruit 100 HIV
infected postmenopausal women for this study who are on a stable antiretroviral therapy (ART)
regimen and randomize them to receive 1000 or 3000 IU of vitamin D daily. The subjects will
be followed closely for one year to monitor compliance and changes in bone health and immune
function.

Inclusion Criteria:

- HIV+ African American and Latina postmenopausal women, aged 40-70, who meet the
standard definition of menopause:

If 50 years old or older then amenorrhea for > 1year. If age 40 to 49 then amenorrhea for
over a year and and Follicle-Stimulating Hormone (FSH) level of equal to or greater than 20
mIU/ml; as some amenorrheic chronically ill women may have hypothalamic dysfunction and low
FSH values, if FSH is 10 to 19, and the serum estradiol level is consistent with menopause
less than or equal to 30pg/ml, she will be determined to be postmenopausal.

- On stable antiretroviral therapy (ART) for >2 years

- Undetectable HIV RNA (viral load) at least 2 times over the past year (RNA <400)

Exclusion Criteria:

- Metabolic bone disease (Paget's disease, clinical osteomalacia, primary
hyperparathyroidism, hypercalcemia)

- Multiple myeloma, solid tumors with metastases;

- Endocrinopathy (hyperthyroidism, untreated hypothyroidism, Cushing's syndrome,
prolactin-secreting pituitary adenoma)

- Renal insufficiency (serum creatinine above 1.5 mg/dl)

- Liver disease (AST, ALT, bilirubin, total alkaline phosphatase activity > twice upper
normal limit);

- Intestinal disorders (celiac disease, pancreatic insufficiency, Crohn's disease,
ulcerative colitis)

- Current use of glucocorticoids, anticonvulsants, anticoagulants, diuretics,
methotrexate;

- Current or past use of drug therapies for osteoporosis (raloxifene, bisphosphonates,
calcitonin, PTH). Women on estrogen are excluded. Past estrogen use is permitted if
discontinued >1 year before enrollment.

- If there is a history of a low trauma fracture, a T score < -3 or a prevalent
vertebral fracture on Instant Vertebral Assessment™ (IVA), subjects will be referred
for osteoporosis treatment as appropriate.

- Severe vitamin D deficiency (25-OHD level <10 ng/ml) or normal baseline serum vitamin
D (25-OHD >32 ng/ml). Subjects with severe vitamin D deficiency may be referred to our
sub-study, if all other inclusion/exclusion criteria are met.

- Hypercalcemia or history of calcium-containing kidney stones

- Known allergy/sensitivity or any hypersensitivity to components of study drugs or
their formulations

- Current imprisonment or voluntary incarceration in a medical facility for psychiatric
illness

- Any condition that, in the opinion of the site investigator, would compromised the
subject's ability to participate in the study