title: Vitamin D₃supplementation in Batswana children and adults with HIV: a pilot double blind randomized controlled trial.
abstract: OBJECTIVE
  Since vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D₃) in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (Δ25D).
  
  
  METHODS
  Prospective randomized double-blind 12-week pilot trial of subjects ages 5.0-50.9 years.
  
  
  METHODS
  Sixty subjects randomized within five age groups to either 4000 or 7000 IU per day of D₃ and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D) ≥32 ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL), CD4%, anti-retroviral therapy (ART) regime, and height-adjusted (HAZ), weight-adjusted (WAZ) and Body Mass Index (BMIZ) Z scores.
  
  
  RESULTS
  Subjects were 50% male, age (mean±SD) 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log₁₀ range of <1.4 to 3.8 and VL detectable (>1.4) in 22%. From baseline to 12 weeks, 25D increased from 36±9 ng/ml to 56±18 ng/ml (p<0.0001) and 68% and 90% had 25D ≥32 ng/ml, respectively (p = 0.02). Δ25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04). HAZ and CD4% increased and VL decreased in the 7000 IU/d group (p<0.04). Younger (5-13y) and older (30-50y) subjects had greater Δ25D than those 14-29y (26±17 and 28±12 vs. 11±11 ng/ml, respectively, p≤0.001). Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p≤0.03).
  
  
  CONCLUSIONS
  In a pilot study in Botswana, 12-week high dose D₃ supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02189902.
authors.affiliation: Botswana-UPenn Partnership, Gaborone, Botswana; Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics and Adolescent Health, School of Medicine, University of Botswana, Gaborone, Botswana.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Steenhoff
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Joan I
authors.initials: JI
authors.lastname: Schall
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Julia
authors.initials: J
authors.lastname: Samuel
authors.affiliation: Botswana-UPenn Partnership, Gaborone, Botswana.
authors.forename: Boitshepo
authors.initials: B
authors.lastname: Seme
authors.affiliation: Botswana-Baylor Children's Clinical Centre of Excellence, Gaborone, Botswana.
authors.forename: Marape
authors.initials: M
authors.lastname: Marape
authors.affiliation: Botswana-UPenn Partnership, Gaborone, Botswana.
authors.forename: Bakgaki
authors.initials: B
authors.lastname: Ratshaa
authors.affiliation: Botswana-UPenn Partnership, Gaborone, Botswana.
authors.forename: Irene
authors.initials: I
authors.lastname: Goercke
authors.affiliation: Botswana-Baylor Children's Clinical Centre of Excellence, Gaborone, Botswana.
authors.forename: Michael
authors.initials: M
authors.lastname: Tolle
authors.affiliation: Department of Nutrition, University of Botswana, Gaborone, Botswana.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Nnyepi
authors.affiliation: Department of Pediatrics and Adolescent Health, School of Medicine, University of Botswana, Gaborone, Botswana.
authors.forename: Loeto
authors.initials: L
authors.lastname: Mazhani
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Babette S
authors.initials: BS
authors.lastname: Zemel
authors.affiliation: Division of General Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Rutstein
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Stallings
mesh_terms: D000293:Adolescent; D000328:Adult; D001902:Botswana; D002648:Child; D002675:Child, Preschool; D002762:Cholecalciferol / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome; D019562:Viral Load; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D