S75 Risk Factors And Therapeutic Implications Of Vitamin D Deficiency In Malawian Adults With Pulmonary Tuberculosis

Abstract

Introduction and objectives Pre-treatment Vitamin D deficiency (VDD) is well described amongst adult TB patients in Malawi and has been associated with impaired mycobacterial immunity. Anti-TB drugs and antiretroviral therapy (ART) for HIV may induce hepatic Vitamin D metabolism, further reducing the serum concentration of active metabolites including 25-OH D3. This study identified risk factors for baseline VDD, assessed the effect of therapy on 25-OH D3 concentrations, and evaluated whether VDD deficiency has prognostic implications for treatment response. Methods Adults with pulmonary TB were treated with standard 6 month therapy. Serum 25-OH D3 concentrations were measured at baseline, 8 weeks and end of treatment. Serial sputum samples were used to model the rate of bacterial elimination for each patient. Patients were followed until 1 year post-treatment and final outcomes were defined as favourable (stable cure) or unfavourable (failure/relapse). Linear and logistic regression analyses were used to identify risk factors for VDD and assess relationships between VDD and treatment response. Results 133 patients were studied. 75 (56%) were HIV-infected and 24 (18%) were on ART. 118 (89%) had favourable and 15 (11%) had unfavourable outcomes. The median baseline 25-OH D3 concentration was 57.3 nmol/l. 47 (28%) patients had concentrations <50 nmol/l, representing VDD. On multivariate analysis, neither HIV status nor ART influenced baseline 25-OH D3 levels, but lower concentrations were reported in patients who were recruited during the cold months of July/August (p = 0.001), suffered food insecurity (p = 0.035) or had a lower baseline Body Mass Index (p = 0.047). Without specific supplementation, 25-OH D3 levels improved during TB therapy (see figure). There were no associations between 25-OH D3 levels at

Impact of Nonlinear Interactions of Pharmacokinetics and MICs on Sputum Bacillary Kill Rates as a Marker of Sterilizing Effect in Tuberculosis

“…These findings suggest that the effect of removing isoniazid from the regimen on long-term outcomes, such as relapse and emergence of resistance, should be evaluated in future studies. Some clinical studies have found a higher isoniazid AUC to be associated with positive treatment outcomes, while the effects of all the other drugs were not significant (42,43). Therefore, the long-term role of isoniazid needs further evaluation.…”

Review of the British Thoracic Society Winter Meeting 2014, 3-5 December, London, UK

“…A higher than expected prevalence of blood-borne viruses in TB cases was confirmed in a separate abstract by Potter et al ,35 who advocated changing national guidelines to recommend routine screening for hepatitis B and C in patients with active tuberculosis. Vitamin D deficiency was an important discussion topic in the 2013 winter meeting review, but in a study by Sloan et al 36 was found not to have any effect on treatment response during TB infection in adults in Malawi.…”