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

David A. Jolliffe, Davaasambuu Ganmaa, Christian Wejse, Rubhana Raqib, M. Ahsanul Haq, Nawal Salahuddin, Peter K. Daley, Anna P. Ralph, Thomas R. Ziegler, Adrian R. Martineau

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    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.

    Original languageEnglish
    Article number1802003
    JournalThe European respiratory journal
    Volume53
    Issue number3
    Early online date7 Mar 2019
    DOIs
    Publication statusPublished - Mar 2019

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    Jolliffe, D. A., Ganmaa, D., Wejse, C., Raqib, R., Haq, M. A., Salahuddin, N., Daley, P. K., Ralph, A. P., Ziegler, T. R., & Martineau, A. R. (2019). Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data. The European respiratory journal, 53(3), [1802003]. https://doi.org/10.1183/13993003.02003-2018