One-step individual participant data meta-analysis: time to sputum culture conversion after initiation of antimicrobial therapy (overall and by subgroup)
| Participants (trials) | Time to sputum culture conversion days | Adjusted HR# (95% CI) | Within-subgroup p-value | p-value for interaction | ||
| Placebo group | Vitamin D group | |||||
| Overall | 820 (4) | 35 (21–49) | 35 (21–49) | 1.06 (0.91–1.23) | 0.44 | |
| Baseline 25(OH)D concentration nmol·L−1 | ||||||
| <25 | 480 (4) | 35 (22–49) | 35 (21–49) | 1.14 (0.93–1.40) | 0.20 | 0.25 |
| ≥25 | 330 (4) | 31 (20–44) | 34 (19–46) | 0.94 (0.75–1.19) | 0.62 | |
| Age years | ||||||
| <30 | 350 (4) | 35 (21–49) | 34 (20–45) | 1.09 (0.87–1.37) | 0.45 | 0.70 |
| ≥30 | 470 (4) | 35 (23–49) | 35 (22–49) | 1.04 (0.85–1.27) | 0.74 | |
| Sex | ||||||
| Male | 559 (4) | 35 (22–49) | 35 (21–49) | 1.10 (0.91–1.32) | 0.32 | 0.53 |
| Female | 261 (4) | 34 (21–47) | 34 (19–44) | 0.99 (0.77–1.29) | 0.97 | |
| MDR isolate | ||||||
| No | 780 (4) | 35 (21–49) | 35 (21–49) | 1.02 (0.88–1.19) | 0.78 | 0.02+ |
| Yes | 37 (4) | >56 (50– >56)¶ | 38 (10– >56)¶ | 13.44 (2.96–60.90) | 0.001 | |
| HIV status | ||||||
| Seronegative | 383 (3) | 29 (20–43) | 29 (16–41) | 1.03 (0.84–1.28) | 0.75 | 0.53 |
| Seropositive | 8 (2) | 21 (9–36) | 39 (10–49) | 0.09 (0.01–0.89) | 0.04 | |
| Zones involved, baseline radiograph % | ||||||
| <50 | 377 (2) | 35 (21–50) | 35 (21–49) | § | § | 0.75 |
| ≥50 | 132 (2) | 37 (28–49) | 36 (33–50) | 1.05 (0.70–1.58) | 0.82 | |
| Cavitation, baseline radiograph | ||||||
| No | 380 (3) | 35 (21–49) | 35 (21–45) | 1.13 (0.90–1.42) | 0.29 | 0.60 |
| Yes | 294 (3) | 36 (22–50) | 35 (21–51) | 1.03 (0.79–1.34) | 0.83 | |
| Vitamin D dosing regimen | ||||||
| Daily/weekly | 165 (1) | 23 (11–37) | 23 (9–37) | § | § | 0.68 |
| Bolus/2-weekly | 655 (3) | 35 (21–49) | 35 (21–49) | 1.08 (0.91–1.28) | 0.39 | |
| FokI VDR genotype | ||||||
| FF | 226 (2) | 36 (23–50) | 35 (21–51) | 0.99 (0.73–1.35) | 0.97 | 0.81 |
| Ff | 221 (2) | 36 (21–50) | 35 (34–49) | 1.20 (0.88–1.64) | 0.24 | |
| ff | 56 (2) | 36 (35–49) | 49 (22–50) | 1.00 (0.55–1.82) | 0.99 | |
| TaqI VDR genotype | ||||||
| TT | 394 (3) | 36 (22–50) | 35 (22–50) | 1.10 (0.88–1.38) | 0.41 | 0.95 |
| Tt | 162 (3) | 36 (21–49) | 35 (21–52) | 0.96 (0.68–1.37) | 0.83 | |
| tt | 42 (3) | 35 (22–53) | 34 (9–40) | 1.54 (0.77–3.08) | 0.22 | |
Data are presented as n or median (interquartile range), unless otherwise stated. 25(OH)D: 25-hydroxyvitamin D; MDR: multidrug-resistant (i.e. resistant to isoniazid and rifampicin at least); VDR: vitamin D receptor. #: adjusted for age, sex and clustering within trials, except for subgroup analysis by age (where age was not adjusted for) and sex (where sex was not adjusted for); ¶: survival times were truncated at 56 days in order to capture effects of adjunctive vitamin D on the standardised background of intensive-phase antimicrobial therapy; values for time to sputum culture conversion of >56 days are therefore indicated as “>56”; +: p-value for interaction for this subgroup analysis remained significant after correction for multiple comparisons testing, using the Benjamini–Hochberg method with a false discovery rate of 20%; §: within-subgroup adjusted hazard ratio and p-value could not be calculated due to nonconvergence of the model.