Forgiveness Is the Attribute of the Strong: Nonadherence and Regimen-Shortening in Drug-Sensitive TB

Helen R Stagg, Jennifer A Thompson, Marc Ci Lipman, Derek J Sloan, Mary Flook, Katherine L Fielding

Research output: Contribution to journalArticlepeer-review

Abstract

RATIONALE: 'Forgiveness' charts the ability of a drug or regimen to withstand non-adherence without negative clinical consequences.

OBJECTIVES: We aimed to determine the influence of regimen length, regimen drugs and dosing, and when during treatment non-adherence occurs on the forgiveness of anti-tuberculosis regimens.

METHODS: Using data from three randomised controlled trials comparing experimental four-month regimens for drug-sensitive tuberculosis with the standard six-month regimen, we used generalised linear models to examine how the risk of a negative composite outcome changed as dose-taking decreased. The percentage of doses taken and absolute number of doses missed were calculated, during the intensive and continuation phases of treatment, and overall. A mediation analysis was undertaken to determine how much of the association between intensive phase dose-taking and the negative composite outcome was mediated through continuation phase dose-taking.

MEASUREMENTS AND MAIN RESULTS: Forgiveness of the four-month and six-month regimens did not differ for any treatment period. Importantly, four-month regimens were no less forgiving of small numbers of absolute missed doses than the six-month regimen (e.g. for 3-7 missed doses versus no missed doses (baseline), six-month regimen adjusted risk ratio 1.65 (95% confidence interval 0.80-3.41) and four-month regimens 1.80 (1.33-2.45)). No four-month regimen was conclusively more forgiving than another. We found evidence of mediation by continuation phase dose-taking on the intensive phase dose-taking and negative composite outcome relationship.

CONCLUSIONS: With the current appetite for, and progress towards, shorter drug-sensitive tuberculosis regimens worldwide, we offer reassurance that shorter regimens are not necessarily less forgiving of non-adherence. Given the importance of continuation phase adherence, patient support during this period should not be neglected.

Original languageEnglish
JournalAmerican Journal of Respiratory and Critical Care Medicine
Early online date11 Aug 2022
DOIs
Publication statusE-pub ahead of print - 11 Aug 2022

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