Vitamin D Supplements for HIV-positive Patients on cART
Condition: HIV-associated Co-morbidities
MeSH terms: HIV Seropositivity
Study type: Interventional

Summary: 
      The ability of vitamin D to modulate the immune system and strengthen bones may mitigate the
      adverse medication consequences of HIV/AIDS, but little is known about either the health
      benefits of vitamin D supplements, or about the optimal dosing regimen for patients on highly
      active antiretroviral therapy (HAART). This trial is a comparison of two regimens for
      administering vitamin D and calcium to HIV-positive individuals taking antiviral medications.
      This study will help physicians make evidence-based decisions about the most effective way to
      use vitamin D in their patients and enable the design of large multi-center trials in the
      future.
    

Detailed description: 
      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.
    

Intervention name(s): conventional vitamin D treatment; tiered/titrated vitamin D dosing
Intervention type(s): Dietary Supplement; Drug
Intervention description(s): Subjects in Protocol A (the conventional/active placebo arm) 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, for a total duration of treatment of 12 mo.
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: HIV; combination antiretroviral therapy; vitamin D; low bone density