A Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Effectiveness of Vitamin D3 50,000 IU Every 4 weeks to Increase Bone Mineral Density and Decrease Tenofovir-Induced Hyperparathyroidism in Youth with HIV Infection Being Treated with Tenofovir-Containing Combination Antiretroviral Therapy (ATN 109 Version 2.0, dated 08/18/2014)
DescriptionThis is a 48 week randomized double-blind, placebo-controlled prospective cohort study of adolescents and young adults with HIV infection in the ATN who are currently being treated with cART that includes TDF as one component of the regimen that includes at least three Food and Drug Administration (FDA)-approved ARVs for at least 180 days. Subjects must have at least one documented viral load that is below 200 copies/mL that is collected following initiation of TDF containing cART and greater than 90 days prior to randomization; no viral load above 200 copies/mL if measured within the 90 days prior to randomization; and an HIV viral load obtained at screening that is below 200 copies/mL. Treatment assignments will be balanced by subject sex at birth, age (<20 years vs. >=20 years), and race (African American vs. other). Enrolled subjects will be randomized to receive vitamin D3 50000 IU or matching placebo, given orally every four weeks by DOT. In addition to the randomized study agent, all subjects will receive a MVI to be taken orally once daily. This "standard" MVI will contain ingredients not to exceed 600 IU of vitamin D3 and 200 mg Ca. DXA measurement of whole-body BMC, and BMD at spine and hip, will be performed at baseline and study weeks 24 and 48. Blood and urine sampling to assess the Ca-PO4 axis, PTH-FGF23-vitamin D signaling, bone turnover, and renal glomerular and tubular function will occur at baseline and study weeks 12, 24, and 48 Blood samples to measure Gluc homeostasis will be drawn at baseline and week 48, and will be run by batch analysis. Safety, measured by SCa and SCr, will be monitored by subject's record review at study sites since these labs will generally be measured as a part of routine clinical care. The ATN109 study will use the SCa and SCr values obtained within 10 weeks at the time of the visit beginning at the baseline visit. If these evaluations were not performed within the prior 10 weeks they will be drawn at the time of the visit. Viral load and CD4 cell count results will be recorded for the ATN109 study at screening, baseline and study weeks 12, 24, 48, and Post-Week 48 provided the evaluations were done within the protocol specified timeframe. If the evaluations are not performed within the protocol specified timeframes they will be drawn at the time of the visit.
Inclusion and Exclusion Criteria
- To be considered eligible for enrollment, an individual must meet the criteria listed below at the time of randomization: NOTE: If the DXA scan is scheduled prior to randomization, , all eligibility criteria must be met prior to performing the DXA scan.
- Age 16 years and 0 days to 24 years and 364 days;
- Behaviorally infected with HIV (e.g., sexual contact, injection drug use; not infected by perinatal transmission, blood transfusion, or at age younger than 9 years);
- HIV-1 infection as documented in subject's medical record by at least one of the following criteria:
- reactive HIV screening test result with an antibody based FDA-licensed assay followed by a positive supplemental assay (e.g., HIV-1 Western Blot, HIV-1 Indirect Immunofluorescence, Antibody Differentiation Assay (Multispot)); or
- positive HIV-1 DNA PCR assay; or
- plasma HIV-1 quantitative RNA assay >1,000 copies/mL; or
- positive plasma HIV-1 RNA qualitative assay
- Subjects must have at least one documented HIV viral load that is below 200 copies/mL collected following initiation of TDF containing cART and greater than 90 days prior to randomization; no HIV viral load above 200 copies/mL if measured within the 90 days prior to randomization; and an HIV viral load obtained at screening that is below 200 copies/mL.
- Currently being treated for at least 180 days by the time of randomization with a TDF containing cART with at least 2 other FDA approved ARVs (NOTE: This may include a TDF-containing fixed drug combination medication);
- Negative serum hepatitis B surface antigen (HBsAg) at screening or by history within 4 weeks prior to screening (see section 7.1.3);
- Willingness and ability to remain on the same cART regimen for the duration of study participation;
- Willingness and ability to participate in the study, follow all study procedures for the duration of study participation, and provide written informed consent or assent with parental permission, if applicable; and
- For females of child-bearing potential, agreement to use a minimum of one proven-effective method of birth control and willingness to postpone pregnancy for the duration of study participation (see section 5.3.2 for permitted hormonal contraceptives)
- To be considered eligible for enrollment, an individual must not meet any of the criteria listed below at the time of randomization: NOTE: If the DXA scan is scheduled prior to randomization, all eligibility criteria must be met prior to performing the DXA scan.
- Prior hypersensitivity to vitamin D;
- History of sarcoidosis, arteriosclerosis, renal stones, glomerulonephritis, interstitial kidney disease, nephrotic syndrome, hypercalcemia, osteoporosis and/or other bone diseases, clinical diagnosis of hypoparathyroidism or hyperparathyroidism;
- Lactation or pregnancy currently or within the past 24 weeks;
- Chemotherapy or radiation therapy for malignancy within the past 12 months;
- Known presence of GI disease that, in the opinion of the clinician, would interfere with study agent administration or absorption (e.g. Crohn's, Colitis);
- For subjects ≥ 18 years, confirmed creatinine clearance < 70 ml/min (estimated GFR from SCr using CG equation) and for subjects <18 years, confirmed creatinine clearance < 70ml/min/1.73m2 (estimated GFR from SCr using Schwartz formula (see section 3.5). (Estimated GFR may be calculated using the formulae programmed on the ATN website;
- SCa > Upper Limit Normal (ULN) for local laboratory values (see section 7.1.3);
- Active Grade 3 or higher clinical or laboratory toxicity except ATV associated indirect hyperbilirubinemia (see section 188.8.131.52);
- Weight is > 350 pounds (lbs) or 159 kilograms (kgs);
- Positive hepatitis C antibody by history or at screening (see section 7.1.3); and
- Use of any medications as specified in sections 5.3.1, 5.3.3 and 5.4.
- Females Only: Use of certain hormonal contraceptives as specified in the protocol.
Please contact Susana Sanchez to learn more about where you can participate in this trial. Please use the contact form on the right side.