Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data

Eur Respir J. 2019 Mar 7;53(3):1802003. doi: 10.1183/13993003.02003-2018. Print 2019 Mar.

Abstract

Background: Randomised controlled trials of adjunctive vitamin D in pulmonary tuberculosis (TB) treatment have yielded conflicting results. Individual participant data meta-analysis could identify factors explaining this variation.

Methods: We meta-analysed individual participant data from randomised controlled trials of vitamin D in patients receiving antimicrobial therapy for pulmonary TB. Primary outcome was time to sputum culture conversion. Secondary outcomes were time to sputum smear conversion, mean 8-week weight and incidence of adverse events. Pre-specified subgroup analyses were done according to baseline vitamin D status, age, sex, drug susceptibility, HIV status, extent of disease and vitamin D receptor genotype.

Results: Individual participant data were obtained for 1850 participants in eight studies. Vitamin D did not influence time to sputum culture conversion overall (adjusted HR 1.06, 95% CI 0.91-1.23), but it did accelerate sputum culture conversion in participants with multidrug-resistant pulmonary TB (adjusted HR 13.44, 95% CI 2.96-60.90); no such effect was seen in those whose isolate was sensitive to rifampicin and/or isoniazid (adjusted HR 1.02, 95% CI 0.88-1.19; p-value for interaction=0.02). Vitamin D accelerated sputum smear conversion overall (adjusted HR 1.15, 95% CI 1.01-1.31), but did not influence other secondary outcomes.

Conclusions: Vitamin D did not influence time to sputum culture conversion overall, but it accelerated sputum culture conversion in patients with multidrug-resistant pulmonary TB.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antitubercular Agents / therapeutic use*
  • Dietary Supplements
  • Drug Resistance, Multiple, Bacterial
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / isolation & purification
  • Randomized Controlled Trials as Topic
  • Receptors, Calcitriol / genetics
  • Sputum / microbiology
  • Tuberculosis, Pulmonary / drug therapy*
  • Vitamin D / administration & dosage*
  • Young Adult

Substances

  • Antitubercular Agents
  • Receptors, Calcitriol
  • VDR protein, human
  • Vitamin D