Vitamin D supplementation in addition to antimicrobial therapy for tuberculosis had no effect on time to sputum culture for patients with tuberculosis, but cut time to sputum culture conversion for multi-drug resistant patients, according to a systematic review and meta-analysis.
Overall, vitamin D had no effect on time to sputum culture conversion (adjusted HR 1.06, 95% CI 0.91-1.23), reported Adrian R. Martineau, PhD, of Queen Mary University of London in England, and colleagues in the European Respiratory Journal.
However, in patients with multi-drug resistant tuberculosis (MDR-TB), adding vitamin D accelerated sputum conversion (adjusted HR 13.44, 95% CI 2.96-60.90) — albeit with an extremely wide confidence interval, they noted.
But they added that nearly 30% of patients with MDR-TB did not receive any second-line antimicrobial therapy, and the analysis is based on a relatively small number of participants.
The researchers noted that vitamin D has generated interest as a potential candidate for an adjunctive host therapy on the basis of its historical use in treating tuberculosis, as well as “the reported associations between vitamin D deficiency and susceptibility to TB infection and disease, and its recognized role in supporting antimycobacterial immune responses.”
But studies in this setting have yielded conflicting results, with some showing favorable effects on either the whole population, subgroups of the population only or no effects at all. Researchers also noted that systematic reviews and aggregate data meta-analyses have been limited by lack of individual participant data.
The primary outcome of this systematic review and meta-analysis was time from initiation of antimicrobial therapy to stable sputum culture conversion “estimated as the mid-point between the last positive sputum culture and the first negative culture.”
Individualized data was obtained for 1,850 participants in eight studies, six of which used parallel arms to investigate the effects of vitamin D. Seven studies administered vitamin D orally to participants in the intervention arm, and one administered vitamin D intramuscularly. Follow-up ranged from 8 weeks to 8 months.
HIV status was tested in 995 participants in five studies, and about 16% tested positive. There were 1,660 participants in six studies with baseline 25(OH)D concentrations, which ranged from undetectable to 250 nmol/L. Of the 1,350 participants in six studies with drug susceptibility testing results, 55 patients tested had MDR-TB. In four trials, the risk of bias was “unclear,” due to >20% of participants being lost to follow-up, the authors said.
While having no significant effect on the primary outcome, the authors described the subgroup analysis finding that vitamin D supplementation “accelerated” sputum culture conversion in patients with MDR-TB as having “potential clinical significance,” and said it was biologically plausible, “since host-directed therapies … are likely to confer greater benefit in scenarios where antimicrobial therapy is less effective.”
However, the authors noted that there was no effect in those whose isolate was sensitive to rifampicin and/or isoniazid (adjusted HR 1.02, 95% CI 0.88-1.19).
Examining secondary outcomes, the authors found that vitamin D accelerated sputum smear conversion (adjusted HR 1.15, 95% CI 1.01-1.31), but there was no difference in other secondary outcomes, such as proportions of participants with negative sputum culture/smear after 8 weeks of antimicrobial therapy, and weight after 8 weeks of antimicrobial therapy.
There were also no differences in secondary safety outcomes, such as hypercalcemia, serious adverse events, study withdrawal, or death due to any cause.
Limitations to the data include that individual participant data was not obtained for two of 10 eligible trials, and that end-of-treatment outcomes were not available for meta-analysis.
Martineau disclosed no conflicts of interest. One co-author disclosed support from the Australian National Health and Medical Research Council.