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BACKGROUND Effective investigation of tuberculosis (TB) contacts is essential for continued progress toward TB elimination. As the incidence of TB declines, staff experience will also decline. Little is known about the association between the experience level of public health TB staff and the quality of contact investigations. METHODS Contact investigations involving fewer than 30 contacts during the period 2008–2009 were included in this analysis. Multivariable models were used to examine associations between staff TB experience (assessed by a standardized survey) and measures of contact investigation quality: time from case identification to contact identification and number of contacts identified per case investigated. RESULTS A total of 501 cases and 3,230 contacts met the inclusion criteria. Data were stratified by the number of cases in the county and whether the case was smear-positive or smear-negative. For contacts of smear-positive cases, greater staff experience was associated with more rapid contact identification both in counties with high case counts (hazard ratio [HR] = 2.43; 95% CI, 1.79–3.31) and in counties with low case counts (HR = 1.142; 95% CI, 0.95–1.37). However, for smear-negative cases, staff in counties with low case counts identified contacts more slowly as years of experience increased (HR = 0.82; 95% CI, 0.62–1.07). For contacts of smear-negative cases, more contacts (relative risk [RR] = 1.20; 95% CI, 1.07–1.35) were identified per case in high case-count counties (more than 20 cases during 2008–2009). Conversely, in low case-count counties, fewer contacts were identified per case (RR = 0.94; 95% CI, 0.82–1.08); however, this finding was not significant. DISCUSSION Speed of identification and number of contacts are imperfect surrogates for the most important outcome of contact investigations—that is, the rapid identification and treatment of infected contacts. CONCLUSION More TB experience was associated with more rapid and thorough TB contact investigations. Retaining experienced staff and mentoring staff new to case management should be high priorities for TB control programs.

Rationale: We developed a standardized method, possible poor treatment response (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT 02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary tuberculosis (TB).Objectives: We describe the use of the PPTR process and evaluate whether the goals of minimizing bias in efficacy endpoint assessment and attainment of relevant data to determine outcomes for all participants were achieved.Methods: A PPTR event was defined as the occurrence of one or more prespecified triggers. Each PPTR required initiation of a standardized evaluation process that included obtaining multiple sputum samples for microbiology.Measurements and Main Results: Among 2,343 participants with culture-confirmed drug-susceptible TB, 454 individuals (19.4%) had a total of 534 individual PPTR events, of which 76.6% were microbiological (positive smear or culture at or after 17 wk). At least one PPTR event was experienced by 92.4% (133 of 144) of participants with TB-related unfavorable outcome and between 13.8% and 14.7% of participants with favorable and not-assessable outcomes. A total of 75% of participants with TB-related unfavorable outcomes had microbiological confirmation of failure to achieve a disease-free cure.Conclusions: Standardized methodologies, such as our PPTR approach, could facilitate unbiased efficacy outcome determinations, improve discrimination between outcomes that are related and unrelated to regimen efficacy, and enhance the ability to conduct pooled analyses of contemporary trials.

Background Tuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 non-inferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had non-inferior efficacy and was safe for the treatment of drug-susceptible pulmonary TB (DS-PTB) compared with the standard 6-month regimen. We explored results among the pre-specified subgroup of people with HIV (PWH). Methods PWH and CD4 + counts ≥100 cells/μL were eligible if they were receiving or about to initiate efavirenz-based antiretroviral therapy (ART). Primary endpoints of TB disease-free survival 12 months post-randomization (efficacy) and ≥ grade 3 adverse events (AEs) on treatment (safety) were compared, using a 6.6% non-inferiority margin for efficacy. Randomization was stratified by site, pulmonary cavitation, and HIV-status. PWH were enrolled in a staged fashion, to support cautious evaluation of drug-drug interactions between rifapentine and efavirenz. Results 2,516 participants from 13 countries in sub-Saharan Africa, Asia, and the Americas were enrolled. Among 194 (8%) microbiologically eligible PWH, the median CD4 + count was 344 cells/μL (interquartile range: 223–455). The rifapentine-moxifloxacin regimen was non-inferior to control (absolute difference in unfavorable outcomes -7.4% [95% CI –20.8% to +6.0%]); the rifapentine regimen was not non-inferior to control (+7.5% [95% CI -7.3% to +22.4%]). Fewer AEs were reported in rifapentine-based regimens (15%) than the control regimen (21%). Conclusions In people with HIV-associated DS-PTB with CD4 + counts ≥100 cells/μL on efavirenz-based ART, the 4-month daily rifapentine-moxifloxacin regimen was non-inferior to the 6-month control regimen and was safe.