A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis

Nat Med. 2018 Nov;24(11):1708-1715. doi: 10.1038/s41591-018-0224-2. Epub 2018 Nov 5.


Tuberculosis kills more people than any other infectious disease. Three pivotal trials testing 4-month regimens failed to meet non-inferiority margins; however, approximately four-fifths of participants were cured. Through a pooled analysis of patient-level data with external validation, we identify populations eligible for 4-month treatment, define phenotypes that are hard to treat and evaluate the impact of adherence and dosing strategy on outcomes. In 3,405 participants included in analyses, baseline smear grade of 3+ relative to <2+, HIV seropositivity and adherence of ≤90% were significant risk factors for unfavorable outcome. Four-month regimens were non-inferior in participants with minimal disease defined by <2+ sputum smear grade or non-cavitary disease. A hard-to-treat phenotype, defined by high smear grades and cavitation, may require durations >6 months to cure all. Regimen duration can be selected in order to improve outcomes, providing a stratified medicine approach as an alternative to the 'one-size-fits-all' treatment currently used worldwide.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / adverse effects
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Phenotype
  • Risk Factors
  • Sputum / drug effects
  • Sputum / microbiology
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / epidemiology
  • Tuberculosis, Multidrug-Resistant / microbiology
  • Tuberculosis, Multidrug-Resistant / pathology
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / epidemiology
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / pathology


  • Antitubercular Agents