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

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; P_interaction=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.