Background Bedaquiline and delamanid offer the possibility of more effective and less toxic multidrug-resistant tuberculosis (MDR-TB) treatment. With this treatment, however, some patients, remain at high risk for an unfavorable treatment outcome. The endTB observational study is the largest multicountry cohort of patients with rifampin-resistant/MDR-TB treated in routine care, according to WHO guidance, with delamanid-and/or bedaquiline-containing regimens. We report frequency of sputum culture conversion within six-months of treatment initiation and risk factors for non-conversion. Methods We included patients with a positive baseline culture who initiated a first endTB regimen prior to April 2018. Two consecutive negative cultures collected > 15 days apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups. Findings 1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%) or both (10%). Of these, 939 (85%) experienced culture conversion within six months. In adjusted analyses, patients with HIV had a lower probability of conversion (0•73 [95% CI: 0•62, 0•84]) than patients without HIV (0•84 [95% CI: 0•79, 0•90]; p=0•03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0•68 [95% CI: 0•57, 0•79]) relative to patients without either (0•89; 95% CI: 0•84, 0•95; p=0•0004). Hepatitis C infection, diabetes mellitus/glucose intolerance, and baseline resistance were not associated with conversion.

Summary Setting Four regions in Kazakhstan where participants were recruited from June 2012 to May 2014. Objective To examine associations between incarceration history and tobacco, alcohol, and drug consumption, and human immunodeficiency virus (HIV) infection and diabetes mellitus (DM) with TB. Design This matched case-control study included 1600 participants who completed a survey on sociodemographics, history of incarceration, tobacco, alcohol and drug use, and HIV and DM diagnosis. Conditional logistic regression analysis was used to examine associations between a TB diagnosis and risk factors. Results Participants who had ever smoked tobacco (aOR 1.73, 95%CI 1.23–2.43, P ≤ 0.01), ever drank alcohol (aOR 1.41, 95%CI 1.03–1.93, P ≤ 0.05), were HIV-positive (aOR 36.37, 95%CI 2.05–646.13, P ≤ 0.05) or had DM (aOR 13.96, 95%CI 6.37–30.56, P ≤ 0.01) were more likely to have TB. Conclusions The association between TB and tobacco use, alcohol use, HIV and DM in Kazakhstan suggests a need for comprehensive intervention and prevention approaches that also address tobacco and alcohol use, DM and HIV.

Background Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings. Methods endTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations. Discussion The lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide. Trial registration ClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.

No abstract

No abstract

Supplemental Digital Content is available in the text

No abstract

No abstract