Pharmacokinetics of anti-TB drugs in children and adolescents with drug-resistant TB: a multicentre observational study from India.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is one of the challenging forms of TB to treat, not only in adults but also in children and adolescents. Further, there is a void in the treatment strategy exclusively for children due to various reasons, including paucity of pharmacokinetic (PK) data on anti-TB drugs across the globe. In this context, the present study aimed at assessing the PK of some of the anti-TB drugs used in DR-TB treatment regimens. METHOD: A multicentre observational study was conducted among DR-TB children and adolescents (n = 200) aged 1-18 years (median: 12 years; IQR: 9-14) treated under programmatic settings in India. Steady-state PK (intensive: n = 89; and sparse: n = 111) evaluation of moxifloxacin, levofloxacin, cycloserine, ethionamide, rifampicin, isoniazid and pyrazinamide was carried out by measuring plasma levels using HPLC methods. RESULTS: In the study population, the frequency of achieving peak plasma concentrations ranged between 13% (for rifampicin) to 82% (for pyrazinamide), whereas the frequency of suboptimal peak concentration for pyrazinamide, cycloserine, moxifloxacin, levofloxacin and rifampicin was 15%, 19%, 29%, 41% and 74%, respectively. Further, the frequency of supratherapeutic levels among patients varied between 3% for pyrazinamide and 60% for isoniazid. In the below-12 years age category, the median plasma maximum concentration and 12 h exposure of moxifloxacin were significantly lower than that of the above-12 years category despite similar weight-adjusted dosing. CONCLUSIONS: Age significantly impacted the plasma concentration and exposure of moxifloxacin. The observed frequencies of suboptimal and supratherapeutic concentrations underscore the necessity for dose optimization and therapeutic drug monitoring in children and adolescents undergoing DR-TB treatment.

Efficacy and tolerability of a 4-month ofloxacin-containing regimen compared to a 6-month regimen in the treatment of patients with superficial lymph node tuberculosis: a randomized trial.

BACKGROUND: Tuberculosis (TB) lymphadenitis is the most common form of extra-pulmonary TB, and the treatment duration is six months. This non-inferiority based randomized clinical trial in South India evaluated the efficacy and safety of a four-month ofloxacin containing regimen in tuberculosis lymphadenitis (TBL) patients. METHODS: New, adult, HIV-negative, microbiologically and or histopathologically confirmed superficial lymph node TB patients were randomized to either four-month oflaxacin containing test regimen [ofloxacin (O), isoniazid (H), rifampicin (R), pyrazinamide (Z) -2RHZO daily/ 2RHO thrice-weekly] or a six-month thrice-weekly control regimen (2HRZ, ethambutol/4RH). The treatment was directly observed. Clinical progress was monitored monthly during and up to 12 months post-treatment, and thereafter every three months up to 24 months. The primary outcome was determined by response at the end of treatment and TB recurrence during the 24 months post-treatment. RESULTS: Of the 302 patients randomized, 298 (98.7%) were eligible for modified intention-to-treat (ITT) analysis and 294 (97%) for per-protocol (PP) analysis. The TB recurrence-free favourable response in the PP analysis was 94.0% (95% CI: 90.1-97.8) and 94.5% (95% CI: 90.8-98.2) in the test and control regimen respectively, while in the ITT analysis, it was 92.7% and 93.2%. The TB recurrence-free favourable response in the test regimen was non-inferior to the control regimen 0.5% (95% CI: -4.8-5.9) in the PP analysis based on the 6% non-inferiority margin. Treatment was modified for drug toxicity in two patients in the test regimen, while one patient had a paradoxical reaction. CONCLUSION: The 4-month ofloxacin containing regimen was found to be non-inferior and as safe as the 6-month thrice-weekly control regimen.

Lung volume reduction surgery versus endobronchial valves: a randomised controlled trial.

BACKGROUND: Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. METHODS: This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. RESULTS: 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 versus BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) versus BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm. CONCLUSION: Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.

Resistance Profiles to Second-Line Anti-Tuberculosis Drugs and Their Treatment Outcomes: A Three-Year Retrospective Analysis from South India.

Background: Patients with first-line drug resistance (DR) to rifampicin (RIF) or isoniazid (INH) as a first-line (FL) line probe assay (LPA) were subjected to genotypic DST using second-line (SL) LPA to identify SL-DR (including pre-XDR) under the National TB Elimination Program (NTEP), India. SL-DR patients were initiated on different DR-TB treatment regimens and monitored for their outcomes. The objective of this retrospective analysis was to understand the mutation profile and treatment outcomes of SL-DR patients. Materials and Methods: A retrospective analysis of mutation profile, treatment regimen, and treatment outcome was performed for SL-DR patients who were tested at ICMR-NIRT, Supra-National Reference Laboratory, Chennai between the years 2018 and 2020. All information, including patient demographics and treatment outcomes, was extracted from the NTEP Ni-kshay database. Results: Between 2018 and 2020, 217 patients out of 2557 samples tested were identified with SL-DR by SL-LPA. Among them, 158/217 were FQ-resistant, 34/217 were SLID-resistant, and 25/217 were resistant to both. D94G (Mut3C) of gyrA and a1401g of rrs were the most predominant mutations in the FQ and SLID resistance types, respectively. Favorable (cured and treatment complete) and unfavorable outcomes (died, lost to follow up, treatment failed, and treatment regimen changed) were recorded in a total of 82/217 and 68/217 patients in the NTEP Ni-kshay database. Conclusions: As per the testing algorithm, SL- LPA is used for genotypic DST following identification of first-line resistance, for early detection of SL-DR in India. The fluoroquinolone resistance pattern seen in this study population corelates with the global trend. Early detection of fluoroquinolone resistance and monitoring of treatment outcome can help achieve better patient management.

Individualised risk in patients undergoing lung volume reduction surgery: the Glenfield BFG score.

Lung volume reduction surgery (LVRS) has been shown to be beneficial in patients with chronic obstructive pulmonary disease, but there is low uptake, partly due to perceived concerns of high operative mortality. We aimed to develop an individualised risk score following LVRS.This was a cohort study of patients undergoing LVRS. Factors independently predicting 90-day mortality and a risk prediction score were identified. Reliability of the score was tested using area under the receiver operating characteristic curve (AUROC).237 LVRS procedures were performed. The multivariate analysis factors associated independently with death were: body mass index (BMI)<18.5 kg·m-2 (OR 2.83, p=0.059), forced expiratory volume in 1 s (FEV1)<0.71 L (OR 5.47, p=0.011) and transfer factor of the lung for carbon monoxide (TLCO) <20% (OR 5.56, p=0.031). A risk score was calculated and total score assigned. AUROC for the risk score was 0.80 and a better predictor than individual components (p<0.01). The score was stratified into three risk groups. Of the total patients, 46% were classified as low risk. Similar improvements in lung function and health status were seen in all groups. The score was introduced and tested in a further 71 patients. AUROC for 90-day mortality in this cohort was 0.84.It is possible to provide an individualised predictive risk score for LVRS, which may aid decision making for both clinicians and patients.

Sputum culture conversion with moxifloxacin-containing regimens in the treatment of patients with newly diagnosed sputum-positive pulmonary tuberculosis in South India.

BACKGROUND: Rapid sputum culture conversion at 2 months indicates the sterilizing capacity and potential of regimens to shorten duration of tuberculosis treatment. We compared results of sputum culture conversion by moxifloxacin and control regimens and identified factors affecting sputum culture positivity after 2 months of treatment. METHODS: Human immunodeficiency virus-uninfected adults with newly diagnosed smear-positive pulmonary tuberculosis were randomized to receive a 3- or 4-month moxifloxacin regimen (moxifloxacin [M], isoniazid [H], rifampicin [R], pyrazinamide [Z], ethambutol [E]) or the control regimen (RHZE thrice weekly). Bacteriological assessments were done at 15, 30, 45, and 60 days of treatment. Because all patients in the moxifloxacin groups received 2 months of daily RHZEM, they were grouped together for analysis. Statistical methods included χ(2) test and logistic regression analysis. RESULTS: Sputum culture conversion was analyzed in 780 (616 in the moxifloxacin group and 164 in the control group) of 801 enrolled patients. Ninety-five percent of 590 patients in the moxifloxacin group and 81% of 151 patients in the control group had negative sputum cultures at month 2 (P < .001). The control regimen, age (≥35 years), initial sputum culture grade (2+ or 3+), and male sex were significantly associated with higher odds of positive sputum cultures at 2 months. CONCLUSIONS: A 5-drug daily regimen with moxifloxacin results in significantly higher sputum culture conversion in the first 2 months compared with a thrice-weekly, 4-drug regimen in patients with newly diagnosed sputum-positive pulmonary tuberculosis.

Evolved design makes ThoraQuik safe and user friendly in the management of pneumothorax and pleural effusion.

BACKGROUND: We have previously described the utility of ThoraQuik, a device designed to be fit for purpose for aspirations of pneumothorax and pleural effusions. We evaluated the safety, efficacy and operator handling of the evolved prototype, ThoraQuik II, which has a lesser profile and a spring loaded Veres needle for added safety. METHODS: A prospective, observational clinical trial with ethics and MHRA approval was conducted in a single centre. Patients with diagnosed pneumothorax (including tension pneumothorax) and pleural effusion were consented and recruited. The ease of device introduction, penetration and ease of use were evaluated. Clinical and radiological improvements were the clinical endpoints and operator feedback was analysed. RESULTS: 20 procedures were performed on patients (mean age: 63.4 years (range: 30-90 years) with 75% male subjects) recruited between September 2008 and August 2009. Nine patients had pneumothorax (tension pneumothorax n=4) and 11 had pleural effusions. 19 patients completed the study with symptomatic and radiological resolution. One patient was withdrawn due to poor pain threshold disproportionate to the procedure. No complications were encountered. 68% had complete clinical and radiological resolution and 32% had partial resolution (these patients needed a definitive drain and hence were not aspirated to completion). The operator feedback in the study rated the device as very good or excellent in 90% patients. CONCLUSIONS: Our study found the use of ThoraQuik II to be safe and easy in draining pneumothorax and pleural effusions. The changes to ThoraQuik II made it more user friendly.

Biomarkers in diagnosing and therapeutic monitoring of tuberculosis: a review.

Tuberculosis (TB) continues to pose a significant health challenge worldwide, emphasizing the importance of prompt diagnosis and efficient monitoring of treatment outcomes for effective disease control. Biomarkers have become increasingly important in the realm of TB diagnoses and treatment. The objective of this comprehensive review is to examine the present state of biomarkers employed in the diagnosis of TB, monitoring the response to treatment, and predicting treatment outcomes. In this study, we undertake a comprehensive examination of the diverse biomarkers utilized in TB diagnoses, spanning molecular, immunological, and other novel methodologies. Furthermore, we examine the potential of biomarkers in the context of therapeutic monitoring, assessment of treatment effectiveness, and anticipation of drug resistance. Additionally, this paper presents future prospects regarding the utilization of biomarkers in the therapy of tuberculosis.

Barriers to research progress for perioperative care practitioners working in cardiothoracic surgery.

Policy and research literature worldwide support the need to build research capacity and capability among non-medical practitioners within healthcare systems. However, there exists a paucity of evidence on whether practitioners in cardiothoracic surgery are attuned to this and on what barriers or enablers exist. A survey was carried out with non-medical practitioners working in cardiothoracic surgery in the United Kingdom to explore attitudes towards health research and audit, and to identify current challenges and barriers to surgical research and audit as perceived by cardiothoracic nurses and allied health professionals. A total of 160 completed questionnaires were returned. 99% of respondents supported the need for research and believed that evidence-based surgical care improves outcomes for patients. Seventy-two percent reported that their employer motivates them to take part in national research or audit but, only 22% were allocated time to do so within their role; 96% reported their interest in being involved in research and audit, yet only 30% believed they had the skills to undertake research, and 96% reported needing additional training. More work is needed to increase awareness, capacity and capability among cardiothoracic surgery care practitioners, and indeed other specialities to achieve research progress.

True thymic hyperplasia causing pure red cell aplasia: a case report.

Pure red cell aplasia caused by true thymic hyperplasia is extremely rare. We report the case of a 25-year-old female diagnosed with pure red cell aplasia. Following a thymectomy confirming true thymic hyperplasia and corticosteroid therapy, complete response was achieved. Patients diagnosed with pure red cell aplasia should be investigated with a computerized tomographic scan to assess for thymic pathology and if present, this should be resected. Follow-up is essential to monitor for recurrence.

Utilization of High-pressure Suction for EBUS-TBNA Sampling in Suspected Lung Cancer.

BACKGROUND: Sample adequacy for immediate molecular testing is paramount in lung cancer. To date, several endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) sampling setups have been evaluated, however, the utilization of high-pressure suction (HPS) has not yet been reported.The aim of this study was to evaluate the utilization of HPS onto the needle and its effect on sample volume and adequacy for molecular testing in patients with suspected lung cancer. METHODS: We retrospectively analyzed 128 consecutive EBUS-TBNA performed for suspected lung cancer. This was confirmed in 109 patients. Other diagnoses confirmed in 12, and 7 referred for surgery. Sixty-three patients (89 targets) had HPS (May to September 2020), and compared with 46 (72 targets) who had standard vacuum syringe suction (October 2019 to March 2020). Several parameters and outcomes evaluated, such as number of needle passes, needle strokes, needle size, target size, positron emission tomography avidity, procedure time, blood content score, sample volume, adequacy for molecular testing, as well as baseline patient characteristics and complication rate. RESULTS: There was no difference between the 2 groups in all baseline parameters and characteristics. In multivariable analysis, HPS was associated with significantly higher sample volume (11.2 vs. 9.1 mm3, P=0.036) and less additional procedures to achieve full molecular profiling (2/52 vs. 7/40, P=0.042), in necrotic targets of non-small cell lung cancer. Diagnostic yields were comparable. CONCLUSION: HPS appears to be simple, no-cost, and safe, promising higher sample volume compared with vacuum syringe suction, and also appears to be associated with higher success of full molecular testing with less additional procedures, in non-small cell lung cancer necrotic targets.

Evaluation of ThoraQuik: a new device for the treatment of pneumothorax and pleural effusion.

BACKGROUND: ThoraQuik is a device with a unique design incorporating an aspiration port and one-way valve controlled by a three-way tap, fit for purpose for the treatment of pneumothorax and pleural effusion. Its use, safety and efficacy were evaluated in a prospective observational trial. METHODS: Stage 1: The safety and ability of the device to penetrate the chest wall and the ease of use were evaluated in patients undergoing thoracoscopic procedures by introducing the device at a second port site under vision. Stage 2: The device was evaluated on patients with pneumothorax and pleural effusion. Clinical and radiological improvement were endpoints and operator feedback was evaluated. RESULTS: Phase 1: 10 patients (mean age: 48.5 years (18-76 years) six men) were studied between May 2005 and March 2007. Satisfactory penetration of the chest wall and safe entry in the pleural space was achieved. Phase 2: 20 patients (mean age: 59 years (24-81 years) 13 men) were recruited between May 2007 and May 2008. 10 patients presented with pneumothorax (tension pneumothorax, n=1) and 10 had pleural effusions. One patient withdrew consent and another patient was withdrawn as there was no fluid on trial aspiration. Of the 18 who completed the study, 10/18 had partial and 7/18 patients had complete resolution with no change in one. The qualitative assessments of the ThoraQuik in terms of ease of use and utility were positive. CONCLUSIONS: ThoraQuik achieves satisfactory penetration of the chest wall. It was safe and easy to use to manage pneumothoraces and pleural effusions.

Use of pedicled latissimus dorsi flap in anterior chest wall reconstruction.

Successful surgical management of chest wall tumours relies on extensive chest wall resection with adequate margins. In large complex tumours, return to form and function is determined by appropriate skeletal and soft tissue reconstruction of the chest wall defect. We report an original case of a large 11×16×3 cm ulcerative basosquamous carcinoma of the anterior chest wall. Soft tissue reconstruction was performed with a unilateral pedicled latissimus dorsi flap. A multidisciplinary approach between thoracic and plastic surgeons was used in the planning, intraoperative and follow-up periods. This case highlights a good long-term functional and cosmetic outcome in complex chest wall reconstruction as a result of successful cross-specialty collaboration.

Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.

INTRODUCTION: Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment. MATERIALS AND METHOD: We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application. RESULTS: Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p<0.001). In the multivariate analysis, the adjusted hazards ratios (HR) for an unfavorable response to TB therapy for extent of involvement, baseline cavitation and persistence (post treatment) were 1.21 (95% CI: 1.01-1.44), 1.73 (95% CI: 1.05-2.84) and 2.68 (95% CI: 1.4-5.12) respectively. A 3+ smear had an HR of 1.94 (95% CI: 0.81-4.64). Further probing into the interaction, among patients with 3+ and 2+ smears, HRs for cavitation were 3.26 (95% CI: 1.33-8.00) and 1.92 (95% CI: 0.80-4.60) while for >2 zones, were 3.05 (95% CI: 1.12-8.23) and 1.92 (95% CI: 0.72-5.08) respectively. Patients without cavitation, zonal involvement <2, and a smear grade less than 2+ had a better prognosis and constituted minimal disease. CONCLUSION: Baseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting "minimal disease", had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens.

Uniportal VATS retrieval of an endobronchial coil migrated through pericardium.

Endobronchial insertion of nitinol coils is a minimally invasive treatment strategy for selected patients with advanced emphysema. Although coil migration into the pleural space has been described by Marchetti et al. (Endobronchial coil penetration into the pleural space. Thorax 2018;73:890-1) [ 1], breach through the pericardium has not been reported to date.

Impact of coronavirus 2019 (COVID-19) on training and well-being in subspecialty surgery: A national survey of cardiothoracic trainees in the United Kingdom.

OBJECTIVES: The coronavirus 2019 (COVID-19) pandemic has overwhelmed health care systems and disrupted routine care internationally. Health care workers face disruption to their work routines and professional development, as well as an elevated risk of infection and morbidity. We sought to establish the impact of the COVID-19 pandemic on the well-being, practice, and progression of all trainees in cardiothoracic surgery in the United Kingdom. METHODS: A 31-item questionnaire was designed, validated, and disseminated via e-mail and an instant-messaging platform. RESULTS: In total, 76 (of 118, 64%) cardiothoracic surgical trainees responded, representing all training grades and programs nationally; 48 (63%) and 24 (32%) were concerned about their physical and mental health, respectively, 25 (33%) had taken time off work due to COVID-19, 65 (86%) had treated patients with COVID-19, 36 of whom (55%) were wearing satisfactory personal protective equipment at the time, 41 (54%) remain concerned about personal protective equipment provision at their institution, 42 (55%) had been redeployed to cover other specialties, and 23 (30%) had encountered ethical dilemmas related to care of patients. There was a significant impact on time spent in outpatient clinics (44% reduction), multidisciplinary team meetings (79% reduction), and operating theaters (78% reduction). In total, 67 (88%) of respondents were concerned about the impact on their training, and 54 (71%) felt that the deviation may require an extension in their planned training time. CONCLUSIONS: The duration and impact of the current pandemic is, as yet, uncertain. Timely sharing of experiences, concerns, and expectations will inform health care and education policy and influence practice in the pandemic era and beyond.

Training cardiothoracic surgeons of the future: The UK experience.

OBJECTIVE: The study aimed to assess targeted simulation courses, including live animal operating, as complementary training tools with regard to 2 key surgical skills in early cardiothoracic surgeon training. METHODS: Twenty UK surgical trainees (equivalent to cardiothoracic surgery resident physicians in the United States) in their first year of residency training were evaluated. Assessment of skills in pulmonary wedge resection and cardiopulmonary bypass were undertaken before and after 2 boot camp-style courses, including live animal operating (boot camp 1 and boot camp 2). Resident performance was evaluated by surgical trainers using objective structured assessment of technical skills matrices. Trainers completed a survey on skill development and trainer confidence in the trainee precourse and postcourse. RESULTS: Trainee assessment scores pre- and postcourses were analyzed using a 2-tailed Wilcoxon signed-rank test demonstrating a significant improvement in trainee performance in boot camp 1 in performing cardiopulmonary bypass (median score, 21 precourse and 28 postcourse; P = .001) and pulmonary wedge resection (median score, 25 precourse and 32 postcourse; P = .012), and in boot camp 2, in performing cardiopulmonary bypass (median score, 28 precourse and 30.5 postcourse; P = .018) and pulmonary wedge resection (median score, 31.5 precourse and 37 postcourse; P = .018). Trainers reported increased confidence and decision-making competency of residents and increased confidence of trainers to allow more participation in management. It was found that 83.3% of trainers would support trainee attendance in subsequent years. CONCLUSIONS: Live animal operating as a component of targeted cardiothoracic surgery skill training courses significantly improves technical skills, builds confidence of surgical trainers in resident physicians' practice, and should be supported by the surgery community.

Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV: A Randomized Clinical Trial.

Importance: The benefit of daily over thrice-weekly antituberculosis therapy among HIV-positive patients with pulmonary tuberculosis (TB) who are receiving antiretroviral therapy remains unproven. Objective: To compare the efficacy and safety of daily, part-daily, and intermittent antituberculosis therapy regimens in the treatment of HIV-associated pulmonary TB. Design, Setting, and Participants: This open-label, randomized clinical trial was conducted by the National Institute for Research in Tuberculosis, south India. Adults infected with HIV with newly diagnosed, culture-positive, pulmonary TB were enrolled between September 14, 2009, and January 18, 2016. Interventions: Patients were randomized to daily, part-daily, and intermittent antituberculosis therapy regimens, stratified by baseline CD4 lymphocyte count and sputum smear grade. Antiretroviral therapy was initiated as per national guidelines. Clinical and sputum microbiological examinations of patients were performed monthly until 18 months after randomization. Adverse events were recorded using standard criteria. Main Outcomes and Measures: The primary outcome was favorable response, defined as treatment completion with all available sputum cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment. Unfavorable responses included treatment failures, dropouts, deaths, and toxic effects among regimens. Results: Of 331 patients (251 [76%] male; mean [SD] age, 39 [9] years; mean [SD] HIV viral load, 4.9 [1.2] log10 copies/mL; and median [interquartile range] CD4 lymphocyte count, 138 [69-248] cells/µL), favorable responses were experienced by 91% (89 of 98), 80% (77 of 96), and 77% (75 of 98) in the daily, part-daily, and intermittent regimens, respectively. With the difference in outcome between daily and intermittent regimens crossing the O'Brien-Fleming group sequential boundaries and acquired rifampicin resistance emergence (n = 4) confined to the intermittent group, the data safety monitoring committee halted the study. A total of 18 patients died and 18 patients dropped out during the treatment period in the 3 regimens. Six, 4, and 6 patients in the daily, part-daily, and intermittent regimens, respectively, had TB recurrence. Conclusions and Relevance: Among HIV-positive patients with pulmonary TB receiving antiretroviral therapy, a daily anti-TB regimen proved superior to a thrice-weekly regimen in terms of efficacy and emergence of rifampicin resistance. Trial Registration: clinicaltrials.gov Identifier: NCT00933790.