Stephanus T. Malherbe, Ray Chen, Xiang Yu, Bronwyn Smith, Xin Liu, Jingcai Gao, Andreas H. Diacon, R Dawson, Michèle Tameris, Hong Zhu, Yahong Qu, Hongjian Jin, Shouguo Pan, Lori E. Dodd, Jing Wang, Lisa C. Goldfeder, Ying Cai, Kriti Arora, Joel Vincent, Kim Narunsky, Keboile Serole, René Goliath, Laylah Da Costa, Arshad Taliep, Saalikha Aziz, Remy Daroowala, Friedrich Thienemann, Sandra Mukasa, Richard Court, Bianca Sossen, Petri Ahlers, Simon C. Mendelsohn, Lisa White, Aurelie Gouel, Chuen‐Yen Lau, Samy Hassan, Lili Liang, Hongfei Duan, Gita Khalili Moghaddam, Praveen Paripati, Saher Lahouar, Michael Harris, Kurt Wollenberg, Brendan M. Jeffrey, Mike Tartakovsky, Alex Rosenthal, Michael Duvenhage, Derek T. Armstrong, Taeksun Song, Jill Winter, Q. Gao, Laura E. Via, R Wilkinson, Gerhard Walzl, Clifton E. Barry
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 ( n = 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.