title: High-dose vitamin D3 supplementation in children and young adults with HIV: a randomized, placebo-controlled trial.
abstract: BACKGROUND
  Suboptimal vitamin D status is prevalent in HIV-infected patients and associated with increased risk of disease severity and morbidity. We aimed to determine 12-month safety and efficacy of daily 7000 IU vitamin D3 (vitD3) versus placebo to sustain increased serum 25-hydroxyvitamin D (25(OH)D) and improve immune status in HIV-infected subjects.
  
  
  METHODS
  This was a double-blind trial of perinatally acquired HIV (PHIV)-infected subjects or behaviorally acquired HIV (BHIV)-infected subjects (5.0-24.9 years). Safety, 25(OH)D-related parameters and immune status were assessed at baseline, 3, 6 and 12 months.
  
  
  RESULTS
  Fifty-eight subjects enrolled (67% male, 85% African American and 64% BHIV) and 50 completed with no safety concerns. In unadjusted analyses, there were no differences between randomization groups at baseline; at 3, 6 and 12 months, 25(OH)D was higher with supplementation than baseline and higher than with placebo (P < 0.05). In adjusted mixed models, in the supplementation group, the fixed effect of 25(OH)D was higher (P < 0.001). Percentage of naive T-helper cells (Th naive%) were significantly (P < 0.01) and T-helper cells (CD4%) marginally (P < 0.10) increased with supplementation in those taking highly active antiretroviral therapy (HAART), and RNA viral load was reduced (P ≤ 0.05). In exploratory linear models, change in 25(OH)D predicted RNA viral load at 3 and 12 months and CD4% at 3 months (P < 0.05).
  
  
  CONCLUSIONS
  Daily 7000 IU vitD3 for 12 months was safe in HIV-infected subjects and effective in increasing 25(OH)D. Supplementation improved some clinically important HIV immune markers in subjects on HAART. Adjunct therapy with high-dose, daily vitD3 for HIV-infected subjects and for those on/off HAART requires further investigation.
authors.affiliation: From the *Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia; †Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania; ‡Allergy and Immunology; and §General Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Stallings
authors.forename: Joan I
authors.initials: JI
authors.lastname: Schall
authors.forename: Mary L
authors.initials: ML
authors.lastname: Hediger
authors.forename: Babette S
authors.initials: BS
authors.lastname: Zemel
authors.forename: Florin
authors.initials: F
authors.lastname: Tuluc
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Dougherty
authors.forename: Julia L
authors.initials: JL
authors.lastname: Samuel
authors.forename: Richard M
authors.initials: RM
authors.lastname: Rutstein
mesh_terms: D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D002648:Child; D002675:Child, Preschool; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D010919:Placebos; D002762:Cholecalciferol