Table 2.

Research gaps organised by steps in the PMTPT cascade of care

Cascade step	Research gaps
Step 1: Identification and linkage to care	Best approaches for linkage to care – examining HIV services, child care services and family health or primary care services Characterise the impact of different strategies in different contexts (modeling studies) Identify acceptability and feasibility of different treatments and models of care (qualitative research)
Step 2: Initial evaluation (testing for TB infection)	Re-evaluation of cost, feasibility, yield and cost-effectiveness of testing for TB infection among household contacts aged ≥5 years Assessment of the benefit of tests for TB infection in PLHIV on ART and/or in settings with lower rates of TB incidence and transmission defined as those with a TB notification rate of <100 TB cases (all forms) per 100,000 population and year Evaluation of more specific TB skin tests and point-of-care IGRA tests when they become available (sensitivity, specificity, predictive ability, and operational cost and feasibility in primary care settings) Longer term: deeper understanding of mechanisms of latency to identify biomarkers of progression
Step 3: Medical evaluation to exclude TB disease and recommend TPT	Evaluation of software for the computer-aided detection of TB on digital CXR, especially in specific risk groups (i.e., children, PLHIV) Cost-effectiveness and feasibility of expanding digital CXR in primary care settings in high and intermediate incidence countries Cost-effectiveness of expanded CXR access, and evaluation of payment for CXR through general health services Longer term: development and assessment of alternative methods to exclude TB disease
Step 4: TPT	Evaluation of regimens of 1–2 months’ duration for efficacy, safety, tolerability and acceptability Patient and provider attitudes to TPT and ways to overcome barriers to acceptance of treatment How to accurately monitor and track adverse events related all TPT regimens in programmatic settings Evaluation of safety of all TPT regimens in pregnant and breastfeeding women Longer term: shorter regimens and/or long acting single-dose regimens (for example ‘depot’ injections of a long-acting agent)

PMTPT = programmatic management of TPT; PLHIV = people living with HIV; ART =antiretroviral therapy; IGRA = interferon-gamma release assay; CXR = chest X-ray; TPT = TB preventive therapy.