HIV-associated Co-morbidities
Conditions
Keywords
HIV, combination antiretroviral therapy, vitamin D, low bone density
Brief 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.
Interventions
DIETARY_SUPPLEMENTconventional vitamin D treatment
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.
DRUGtiered/titrated vitamin D dosing
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.
Sponsors
National Institute on Drug Abuse (NIDA)
Andrea Branch
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 25(OH)D Levels | baseline and 12 months | The difference in the percentage of subjects with 25(OH)D levels in the range of 30-60 ng/ml at 12 mo between the two arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD4+T Cell Count | baseline and 12 months | The change in the CD4+T cell count between the two arms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Conventional Vitamin B Dosing 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. | 32 |
| Tiered/Titrated Vitamin B Dosing tiered/titrated vitamin D dosing: Subjects in Protocol B received 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. | 30 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 5 |
Baseline characteristics
| Characteristic | Tiered/Titrated Vitamin B Dosing | Conventional Vitamin B Dosing | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 32 Participants | 62 Participants |
| Age, Continuous | 48 years | 47 years | 48 years |
| Region of Enrollment United States | 30 participants | 32 participants | 62 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 24 Participants | 25 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 30 |
| other Total, other adverse events | 0 / 32 | 0 / 30 |
| serious Total, serious adverse events | 0 / 32 | 0 / 30 |
Outcome results
Primary
25(OH)D Levels
The difference in the percentage of subjects with 25(OH)D levels in the range of 30-60 ng/ml at 12 mo between the two arms.
Time frame: baseline and 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conventional Vitamin D Treatment | 25(OH)D Levels | 13 Participants |
| Tiered/Titrated Vitamin D Dosing | 25(OH)D Levels | 20 Participants |
Secondary
CD4+T Cell Count
The change in the CD4+T cell count between the two arms.
Time frame: baseline and 12 months
Population: Analysis only for participants who completed the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conventional Vitamin D Treatment | CD4+T Cell Count | 26 cell/μL |
| Tiered/Titrated Vitamin D Dosing | CD4+T Cell Count | 40 cell/μL |