Section 4. Regimens for rifampicin-susceptible, isoniazid-resistant TB (Hr-TB)

The development of the current recommendations was made possible by the availability of a global Hr-TB IPD. As in other IPD analyses conducted to inform WHO treatment guidelines in recent years, the Hr-TB IPD analysis facilitated the comparison of different patient groups, some adjustment for covariates and better interpretation of the results (57). It is important for researchers and national programmes to continue contributing patient records to the Hr-TB IPD, to increase its value as a source of information for future treatment policy.

All the recommendations were conditional and were based on very low certainty in the estimates of effect; thus, further research is needed to inform the refinement of policies to optimize the treatment of Hr-TB. The GDG identified various research priorities, including the following:

  1. the need for RCTs evaluating the efficacy, safety and tolerability of regimens for Hr-TB, and for cases with additional resistance to other medicines such as ethambutol or pyrazinamide (e.g. polydrug resistance);
  2. research to clarify the potential benefits and risks of treatment with high-dose isoniazid;
  3. high-quality studies on optimizing the composition and duration of regimens in children and adults, particularly of high-dose isoniazid, fluoroquinolones and other second-line medicines, and of reducing the duration of pyrazinamide;
  4. modelling studies to estimate the number-needed-to-treat for empirical use of an Hr-TB regimen, balancing risks and benefits;
  5. high-quality studies on treatment prolongation among PLHIV;
  6. high-quality studies evaluating regimens for extrapulmonary or disseminated TB;
  7. feasibility of developing FDCs for REZ alone (with or without integrating levofloxacin);
  8. monitoring patient response by isoniazid resistance genotype (e.g. katG versus inhA mutations), either in an individual patient or in a population;
  9. cost–effectiveness of different approaches to DST, including rapid testing of all TB patients for both isoniazid and rifampicin resistance before the start of treatment;
  10. participatory action research within communities and with other stakeholders (e.g. field practitioners and community workers) to explore sociocultural factors that can facilitate treatment adherence and influence outcomes; and
  11. effect of underlying fluoroquinolones and isoniazid polydrug resistance on treatment outcomes.  

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