Higher serum 25-hydroxyvitamin D concentrations are associated with active pulmonary tuberculosis in hospitalised HIV infected patients in a low income tropical setting: a cross sectional study

Abstract

Background: The inherent risk of developing tuberculosis (TB) in HIV- infected individuals is further enhanced by hypovitaminosis D. Interventions that offset HIV-associated immune deterioration potentially arrest disease progression and incidence of opportunistic infections including TB. Despite conflicting reports on association between vitamin D deficiency (VDD) and risk of TB, vitamin D (VD) supplementation remains a promising intervention.

Methods: We conducted a comparative cross-sectional study on 145 HIV⁺/pulmonary TB⁺ (PTB) and 139 HIV⁺/PTB^- hospitalised patients to investigate association of vitamin D status and risk of PTB. Stratified random sampling was used to select archived serum specimens from participants enrolled in a randomised controlled trial (RCT) conducted to investigate the impact of using a point-of-care urine lipoarabinomannan strip test for TB diagnosis. PTB status was confirmed using sputum smear microscopy, culture or GeneXpert MTB/RIF. Serum 25-hydroxyvitamin D [25(OH) D] concentrations were assayed by competitive chemiluminescent immunoassay prior to commencement of anti-TB treatment. Effect of VD status on duration of hospital stay and patient outcomes on follow up at 8 weeks were also investigated. Median serum 25(OH) D concentrations were compared using Mann-Whitney test and covariates of serum VD status were assessed using logistic regression analysis.

Results: Overall VDD prevalence in the cohort was 40.9% (95% CI: 35.1-46.8). Median serum 25(OH)D concentrations were significantly higher in HIV⁺/PTB⁺ group (25.3 ng/ml, IQR:18.0-33.7) compared to the HIV⁺/PTB^- group (20.4 ng/ml, IQR:14.6-26.9), p = 0.0003. Patients with serum 25(OH) D concentration ≥ 30 ng/ml were 1.9 times more likely to be PTB⁺ compared to those with serum 25(OH) D concentrations < 30 ng/ml (odds ratio (OR) 1.91; 95% CI 1.1-3.2). PTB-related death was associated with higher odds of having 25(OH) D levels≥30 ng/ml. Age, gender, CD4⁺ count, combination antiretroviral therapy (cART) status, efavirenz based cART regimen and length of hospital stay were not associated with vitamin D status.

Conclusions: The finding of an association between higher serum 25(OH) D concentrations and active PTB and TB-related mortality among hospitalised HIV-infected patients in the present study is at variance with the commonly reported association of hypovitaminosis and susceptibility to TB. Our findings though, are in concordance with a small pool of reports from other settings.

Keywords: HIV; Hospital stay; Pulmonary tuberculosis; Vitamin D deficiency; cART.

Fig. 1

Box and whisker plot showing the distribution of serum vitamin D concentrations by PTB status. Median serum 25(OH) D concentrations were significantly higher in HIV⁺/PTB⁺ group compared to HIV⁺/PTB⁻ group (p = 0.0003). Key: HIV+ = Human Immunodeficiency Virus positive, PTB+ = Pulmonary Tuberculosis positive, PTB- = Pulmonary Tuberculosis negative