patient has pre-existing hepatic disease, is experiencing symptoms of toxicity or is taking other hepatotoxic medications [61]. Follow-up CXRs are not routinely recommended except in cases of MDR-TB and in those with poor treatment response. For the child’s treatment to be successful without interruption, the adult caregiver must be involved in the treatment plan. Adherence is one of the key determinants for successful treatment, and adolescents in particular experience substantial barriers to treatment adherence and are at risk for loss to follow-up from TB care. Adherence interventions (e.g. treatment support, digital technologies, adherence enablers) have been linked to better outcomes [65]. Despite limited data on their performance in children, remote adherence support techniques such as video-supported observed therapy have transformed adherence monitoring [65]. It is therefore important for TB programmes to implement mechanisms to follow up and monitor children on TB treatment. This includes assignment of outcomes upon treatment completion in line with WHO definitions. The latter have been revised into uniform outcomes that apply to both DS- and MDR-TB in the context of the newer treatment durations [66]. Counselling and health education of children, adolescents and caregivers, as well as nutritional screening, assessment and management, are integral components of TB treatment and care. The management and follow-up of children with TB and other comorbidities (e.g. HIV) present additional challenges related to drug–drug interactions and toxicity overlap (table 5). The drug– drug interactions can be bidirectional (e.g. antiretroviral drugs may have an effect on anti-TB medicines and vice versa). HIV infection has been linked to subtherapeutic levels of the four first-line TB medicines resulting in lower peak concentrations and areas under the curve [67–69]. Rifampicin significantly lowers drug concentrations of antiretroviral drugs (including non-nucleoside reverse transcriptase inhibitors, protease inhibitors and integrase inhibitors) because it induces the cytochrome P450 system, P-glycoprotein and UDP glucuronosyl- transferase [63, 70]. The recently conducted ODYSSEY trial (A randomised trial of dolutegravir- based antiretroviral therapy versus standard of care in children with HIV infection starting first-line or switching to second-line ART) confirmed that twice-daily dolutegravir in HIV-positive children receiving rifampicin is safe and counters the effects of rifampicin enzyme induction [63]. The optimal antiretroviral regimen for children includes dolutegravir-based regimens, so drug or dose adjustments to reduce potential drug–drug interactions should be considered [71]. It should be noted that drug interactions between antiretroviral medications and rifampicin occur both in the treatment of TB disease and when rifampicin is used as TPT. Post-TB lung disease Post-TB disease, including post-TB lung disease (PTLD), causes ill health, poor quality of life and death. PTLD refers to a range of pulmonary complications that occur after a TB episode TABLE 6 Continued Better understand the barriers to diagnosis, treatment and treatment retention among children, adolescents and their families Evaluate the preferences and needs of children, adolescents and their families with respect to TB diagnosis and treatment Develop programmes to reduce stigma among children and adolescents and their families affected by TB Evaluate the implementation of the new WHO-recommended TB treatment regimens for DS-TB (including TBM) and MDR-TB (standardised shorter and longer individualised treatment regimens) in programme settings Evaluate the implementation of the shorter treatment options for TBI and the WHO-recommended algorithm for TB exclusion prior to TPT in programme settings CNS: central nervous system mWRD: molecular WHO-recommended rapid diagnostics DS-TB: drug-susceptible TB TBM: tuberculous meningitis. Data from [27, 76, 77]. 230 https://doi.org/10.1183/2312508X.10025322 ERS MONOGRAPH |THE CHALLENGE OF TB IN THE 21ST CENTURY