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

David A. Jolliffe, Davaasambuu Ganmaa, Christian Wejse, Rubhana Raqib, Md. Ahsanul Haq, Nawal Salahuddin, Peter K. Daley, Anna P. Ralph, Thomas R. Ziegler, Adrian R. Martineau
European Respiratory Journal 2019; DOI: 10.1183/13993003.02003-2018
David A. Jolliffe
1Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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Davaasambuu Ganmaa
2Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
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Christian Wejse
3School of Public Health, Aarhus University, Aarhus, Denmark
4Bandim Health Project, Statens Serum Institute, Bissau, Guinea-Bissau
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Rubhana Raqib
5International Centre for Diarrheal Disease Research, Dhaka, Bangladesh
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Md. Ahsanul Haq
5International Centre for Diarrheal Disease Research, Dhaka, Bangladesh
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Nawal Salahuddin
6King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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Peter K. Daley
7Memorial University, St John's, Newfoundland, Canada
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Anna P. Ralph
8Menzies School of Health Research, Darwin , Australia
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Thomas R. Ziegler
9Emory University School of Medicine, Atlanta, Georgia, USA
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Adrian R. Martineau
1Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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Abstract

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

Methods We meta-analysed IPD from RCTs of vitamin D in patients receiving antimicrobial therapy for PTB. 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 sub-group analyses were done according to baseline vitamin D status, age, sex, drug-susceptibility, HIV status, extent of disease, and vitamin D receptor genotype.

Results IPD were obtained for 1850 participants in 8 studies. Vitamin D did not influence time to sputum culture conversion overall (aHR 1.06, 95% CI 0.91–1.23), but it did accelerate sputum culture conversion in participants with multidrug-resistant PTB (aHR 13.44, 95% CI 2.96–60.90); no such effect was seen in those whose isolate was sensitive to rifampicin and/or isoniazid (aHR 1.02, 95% CI 0.88–1.19; Pinteraction=0.02). Vitamin D accelerated sputum smear conversion overall (aHR 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 PTB.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. JOLLIFFE has nothing to disclose.

Conflict of interest: Dr. Ganmaa has nothing to disclose.

Conflict of interest: Dr. Wejse has nothing to disclose.

Conflict of interest: Dr. Raqib has nothing to disclose.

Conflict of interest: Dr. Haq has nothing to disclose.

Conflict of interest: Dr. Salahuddin has nothing to disclose.

Conflict of interest: Dr. Daley has nothing to disclose.

Conflict of interest: Dr. Ralph reports grants from Australian National Health and Medical Research Council, during the conduct of the study.

Conflict of interest: Dr. Ziegler has nothing to disclose.

Conflict of interest: Dr. Martineau has nothing to disclose.

This is a PDF-only article. Please click on the PDF link above to read it.

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Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data
David A. Jolliffe, Davaasambuu Ganmaa, Christian Wejse, Rubhana Raqib, Md. Ahsanul Haq, Nawal Salahuddin, Peter K. Daley, Anna P. Ralph, Thomas R. Ziegler, Adrian R. Martineau
European Respiratory Journal Jan 2019, 1802003; DOI: 10.1183/13993003.02003-2018

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Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data
David A. Jolliffe, Davaasambuu Ganmaa, Christian Wejse, Rubhana Raqib, Md. Ahsanul Haq, Nawal Salahuddin, Peter K. Daley, Anna P. Ralph, Thomas R. Ziegler, Adrian R. Martineau
European Respiratory Journal Jan 2019, 1802003; DOI: 10.1183/13993003.02003-2018
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