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

BackgroundThe 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.MethodsWe 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.ResultsOverall 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.ConclusionsThe 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.

Potentials of Host-Directed Therapies in Tuberculosis Management

“…In addition, Vitamin D may also inhibit M. tb growth by enhancing the ability of monocytes to respond to IFN-gamma [26]. It then seems promising to use Vitamin D supplementation for individuals more susceptible to M. tb infection, such as HIV patients [27]. However, there are conflicting reports regarding the effectiveness of serum-25 hydroxyvitamin D in cases of active pulmonary tuberculosis.…”

“…However, there are conflicting reports regarding the effectiveness of serum-25 hydroxyvitamin D in cases of active pulmonary tuberculosis. In one cross-sectional study, it was determined that HIV patients, testing positive for pulmonary TB, still had greater serum levels of 25-hydroxyvitamin D [27]. While this is at variance with other reports, there are still clinical trials demonstrating beneficial potential of adjunctive vitamin D supplementation.…”

Vitamin D and Hemostasis Parameters in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients with Pulmonary Tuberculosis Coinfections

“…Various things may affect Vitamin D levels in HIV/AIDS patients with and without pulmonary TB D. In addition, the complication may also play a role in the intensity of sunlight exposure, malnutritional, and decreased oral intake [20], [21] ART also plays a role in decreased Vitamin D levels. EFV poses a risk for Vitamin D deficiency by increasing the catabolism of 25(OH)D and production of inactive metabolites through interaction with CYP450 enzyme in the form of CYP24A1 induction, which converts 25(OH)D into its inactive form, 24,25(OH) 2 D, as well as reduction of CYP2R1 transcription which inhibits the hydroxylation of Vitamin D3 and Vitamin D2 [20], [21], [22].…”

Host-Directed Therapies and Anti-Virulence Compounds to Address Anti-Microbial Resistant Tuberculosis Infection

“…Moreover, vitamin D enhances the ability of monocytes to respond to interferon gamma (IFN-γ) [47]. Various clinical trials which included vitamin D in addition to the standard regimen have been performed, sometimes with variable results [48][49][50]. It seems evident that key issues for successful use of vitamin D in TB therapy are proper dosing and possibly also genetic background and comorbidities of the patient.…”