Clinical testing of drug treatment shortening in patients with TB using PET/CT imaging of lung lesions.
Authors
Affiliations (26)
Affiliations (26)
- DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Immunology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
- Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
- Henan Provincial Chest Hospital, Zhengzhou, Henan, China.
- Sino-US Tuberculosis Collaborative Research Program, Zhengzhou, Henan, China.
- TASK, Cape Town, South Africa.
- Division of Pulmonology, Department of Medicine, University of Cape Town Lung Institute, Centre for TB Research Innovation, Observatory 7923, Republic of South Africa.
- South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town, Observatory 7923, Republic of South Africa.
- Kaifeng City Institute of Tuberculosis Prevention and Control, Kaifeng, Henan, China.
- Xinmi Center for Disease Control and Prevention, Xinmi, Henan, China.
- Zhongmu County Health and Epidemic Prevention Station, Zhongmu, Henan, China.
- Clinical Trials Research and Statistics Branch, Office of Biostatistics Research, Division of Clinical Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
- Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
- University of Cape Town Lung Institute (Pty) Ltd., Mowbray, Cape Town 7700, Republic of South Africa.
- Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, Republic of South Africa.
- Department of Internal Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
- Department of Medicine, University of Cape Town, Observatory 7923, Republic of South Africa.
- HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
- Beijing Chest Hospital, Beijing, China.
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
- Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA.
- Research Data and Communication Technologies Inc., Garrett Park, MD, USA.
- Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
- Catalysis Foundation for Health, San Ramon, CA, USA.
- School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai, China.
- Francis Crick Institute, London NW1 1AT, UK.
- Department of Infectious Diseases, Imperial College London, London W12 0NN, UK.
Abstract
Six months of drug treatment is standard of care for drug-sensitive pulmonary tuberculosis (TB). Understanding the factors determining the length of treatment required for durable cure would allow individualization of treatment durations. We conducted a prospective, randomized, controlled noninferiority trial (PredictTB) of 4 versus 6 months of chemotherapy in patients with pulmonary TB in South Africa and China. Seven hundred and four participants with newly diagnosed, drug-sensitive TB were enrolled and stratified on the basis of radiographic disease characteristics assessed by FDG PET/CT imaging. Participants with less extensive disease (<i>n</i> = 273) were randomly assigned at week 16 to complete therapy after 4 months or continue receiving treatment for 6 months. This study was stopped early after an interim analysis revealed that patients assigned to the 4-month treatment arm had a higher risk of relapse. Among participants who received 4 months of chemotherapy, 17 of 141 (12.1%) experienced TB-specific unfavorable outcomes compared with only 2 of 132 (1.5%) who completed 6 months of treatment. In the nonrandomized arm that included participants with more extensive disease, only 8 of 248 (3.2%) experienced unfavorable outcomes. Total lung cavity volume and lesion glycolysis at week 16 were associated with the risk of unfavorable outcomes. PET/CT imaging at TB recurrence showed that bacteriological relapses predominantly occurred in active cavities originally present at baseline. Subsequent post hoc automated segmentation of serial PET/CT scans combined with machine learning enabled the classification of participants according to their likelihood of relapse.