Diabetes mellitus (DM) and tuberculosis (TB) are two common diseases with increasing geographic overlap and clinical interactions. The effect of DM and hemoglobin A1c (HbA1c) values on the pharmacokinetics (PK) and pharmacodynamics (PD) of anti-TB drugs remains poorly characterized. Newly diagnosed TB patients with and without DM starting fixed-dose, thrice-weekly treatment underwent sampling for PK assessments (predose and 0.5, 2, and 6 h postdose) during the intensive and continuation phases of treatment. The effect of DM and HbA1c values on the maximum concentration ( ) of rifampin, isoniazid, and pyrazinamide and the association between drug concentrations and microbiologic and clinical outcomes were assessed. Of 243 patients, 101 had DM. Univariate analysis showed significant reductions in the of pyrazinamide and isoniazid (but not rifampin) with DM or increasing HbA1c values. After adjusting for age, sex, and weight, DM was associated only with reduced pyrazinamide concentrations (adjusted geometric mean ratio = 0.74, = 0.03). In adjusted Cox models, female gender (adjusted hazards ratio [aHR] = 1.75, = 0.001), a lower smear grade with the Xpert assay (aHR = 1.40, < 0.001), and the pyrazinamide (aHR = 0.99, = 0.006) were independent predictors of sputum culture conversion to negative. Higher isoniazid or rifampin concentrations were associated with a faster time to culture conversion in patients with DM only. A pyrazinamide above the therapeutic target was associated with higher unfavorable outcomes (treatment failure, relapse, death) (odds ratio = 1.92, = 0.04). DM and higher HbA1c values increased the risk of not achieving therapeutic targets for pyrazinamide (but not rifampin or isoniazid). Higher pyrazinamide concentrations, though, were associated with worse microbiologic and clinical outcomes. DM status also appeared to influence PK-PD relationships for isoniazid and rifampin.

BackgroundIndia accounts for nearly one-quarter of the global tuberculosis (TB) burden. Directly observed treatment (DOT) through in-person observation is recommended in India, although implementation has been heterogeneous due largely to resource limitations. Video DOT (vDOT) is a novel, smartphone-based approach that allows for remote treatment monitoring through patient-recorded videos. Prior studies in high-income, low disease burden settings, such as the United States, have shown vDOT to be feasible, although little is known about the role it may play in resource-limited, high-burden settings.ObjectiveThe goal of the research was to assess the feasibility and acceptability of vDOT for adherence monitoring within a resource-limited, high TB burden setting of India.MethodsWe conducted a prospective, single-arm, pilot implementation of vDOT in Pune, India. Outcome measures included adherence (proportion of prescribed doses observed by video) and verifiable fraction (proportion of prescribed doses observed by video or verbally confirmed with the patient following an incomplete/unverifiable video submission). vDOT acceptability among patients was assessed using a posttreatment survey.ResultsA total of 25 patients enrolled. The median number of weeks on vDOT was 13 (interquartile range [IQR] 11-16). Median adherence was 74% (IQR 62%-84%), and median verifiable fraction was 86% (IQR 74%-98%). More than 90% of patients reported recording and uploading videos without difficulty.ConclusionsWe have demonstrated that vDOT may be a feasible and acceptable approach to TB treatment monitoring in India. Our work expands the evidence base around vDOT by being one of the first efforts to evaluate vDOT within a resource-limited, high TB burden setting. To our knowledge, this is the first reported use of vDOT in India.

Background Diabetes mellitus (DM) increases the risk of tuberculosis (TB) disease. Knowledge of the impact of DM on TB treatment outcomes is primarily based on retrospective studies. Methods We conducted a prospective cohort study of new pulmonary TB patients with and without DM (TB-DM and TB-only) in India. The association of DM with a composite unfavorable TB treatment outcome (failure, recurrence, mortality) over 18 months was determined and the effect of DM on all-cause mortality and early mortality (death during TB treatment) was assessed. Results Of 799 participants, 574(72%) had TB-only and 225(28%) had TB-DM. The proportion of patients with DM who experienced the composite outcome was 20% as compared to 21% for TB only participants (adjusted hazard ratio 1.13, 95% CI 0.75–1.70). Mortality was higher in participants with DM (10% vs. 7%), and early mortality was substantially higher among patients with DM (adjusted hazard ratio [aHR] 4.36; 95% CI:1·62–11.76). Conclusion DM was associated with early mortality in this prospective cohort study, but overall unfavorable outcomes were similar to participants without DM. Interventions to reduce mortality during TB treatment among people with TB-DM are needed.

SUMMARY SETTING: Pune, India. OBJECTIVES: To estimate the prevalence and risk factors of pre-diabetes mellitus (DM) and DM, and its associations with the clinical presentation of tuberculosis (TB). DESIGN: Screening for DM was conducted among adults (age ⩾ 18 years) with confirmed TB between December 2013 and January 2017. We used multinomial regression to evaluate the risk factors for pre-DM (glycated hemoglobin [HbA1c] ⩾ 5.7–6.5% or fasting glucose 100–125 mg/dl) and DM (HbA1c ⩾ 6.5% or fasting glucose ⩾ 126 mg/dl or random blood glucose > 200 mg/dl or self-reported DM history/treatment) and the association of dysglycemia with the severity of TB disease. RESULTS: Among 1793 participants screened, 890 (50%) had microbiologically confirmed TB. Of these, 33% had pre-DM and 18% had DM; 41% were newly diagnosed. The median HbA1c level among newly diagnosed DM was 7.0% vs. 10.3% among known DM (P < 0.001). DM (adjusted OR [aOR] 4.94, 95%CI 2.33–10.48) and each per cent increase in HbA1c (aOR 1.42, 95%CI 1.01–2.01) was associated with >1+smear grade or ⩽9 days to TB detection. CONCLUSION: Over half of newly diagnosed TB patients had DM or pre-DM. DM and increasing dysglycemia was associated with higher bacterial burden at TB diagnosis, potentially indicating a higher risk of TB transmission to close contacts.