Table 1 Summary of model inputs (see Additional file 1 for details and numerical estimates)

Prevalence of “latent progressor” state among each cohort considered for TPT

Latent infections that will progress to active (symptomatic) TB disease at some time in the future

Lifetime cumulative incidence extrapolated from observed 12-month incidence (PWH cohort) or baseline prevalence (household contacts) using published cohort studies and meta-analyses

Table S1

Prevalence of “subclinical progressor” state among each cohort considered for TPT

TB disease that is undetectable by a symptom screen but is microbiologically active and will eventually progress to active disease if untreated

Primary clinical data (Table 2):

Symptom-negative individuals who progressed to active TB within 3 months (PWH) or who were diagnosed with TB during extensive baseline evaluation (household contacts, with adjustment for expected spontaneous resolution).

Table S1

Efficacy of TPT for latent progressors, by regimen

Proportion of latent progressions prevented, if initially susceptible to the TPT regimen and completes enough TPT to be at risk for acquired resistance

Network meta-analysis of clinical trial data, adjusted for reinfection, nonadherence, and baseline drug resistance.

6H efficacy parametrized relative to 4R and assumed equal or less than 4R.

Table S2

Reduction in TPT efficacy when used during subclinical TB

Proportion of TPT-preventable latent progressions that cannot be cured by TPT at the subclinical progressor stage

Bounded by the efficacy of TPT for latent TB and by the efficacy of monotherapy for symptomatic active TB.

Table S2

Risk of acquiring resistance to the TPT drug, if latent TB progresses despite TPT

Applies to those whose TPT is unsuccessful and whose initial infections were not drug-resistant.

Incidence of drug-resistant TB after TPT in clinical trials, adjusted for expected incidence from pre-existing drug resistance. Risk for isoniazid sets an upper bound on risk for rifampicin.

Table S3

Risk of acquiring resistance to the TPT drug, if subclinical TB progresses despite TPT

As above

Treatment trials with a single effective drug. Large uncertainty is reflected in wide parameter distributions.

Table S3

Outcomes after active TB treatment

Risk of failure/relapse, with or without acquired isoniazid or rifampicin resistance, as a function of initial susceptibilities.

Previous reviews of clinical trial and research cohort outcomes. Weighted based on the regimens expected to be used in present-day programmatic settings, including the use of first-line regimens when drug resistance goes undetected.

Table S4

Prevalence and overlap of INH and RIF resistance

Same for subclinical cases and latent progressors

Drug resistance survey data; lower in contacts of DS-TB patients than among all TB infections

Table S4

Baseline drug resistance

Prevalence and overlap of isoniazid and rifampicin resistance among TB infections in a modeled cohort.

National or regional drug resistance survey data, adjusted downward for household contacts of known DS-TB patients

Table S5