Section 1. The 6-month BPaLM regimen for treatment of MDR/RR-TB or pre-XDR-TB

Further research is needed in the following areas:

  1. the efficacy, safety and tolerability of the BPaLM/BPaL regimen for subpopulations for whom current data are limited or missing; that is, children aged below 14 years, patients with extrapulmonary TB, People with HIV with CD4 counts below 100, and pregnant and lactating women;
  2. data from other regions and countries (beyond countries with sites included in recent studies);
  3. description of the mechanism and molecular markers of pretomanid resistance, allowing development of the DST, clinical implications of the lineage 1 effect on efficacy of pretomanid,50 cross-resistance with delamanid and surveillance for the development of resistance, with adequate consideration paid to the impact of selected mutations;
  4. documenting the full adverse event profile of pretomanid, and the frequency of relevant adverse events, with a focus on hepatotoxicity and reproductive toxicity in humans (studies ongoing);
  5. exploring the relative efficacy (and added value in multidrug regimens) of pretomanid and delamanid;
  6. studies capturing outcomes for which currently evidence is scarce (e.g. acquisition of drug resistance and quality of life);
  7. research on geographical differences in the frequency and severity of linezolid-related adverse events and the underlying cause (north–south differences were observed in post-hoc analyses of large and unexplained differences in linezolid-related adverse events between sites);
  8. exploring the possibility of replacing moxifloxacin with levofloxacin;
  9. exploring the extent of cross-resistance between bedaquiline and clofazimine;
  10. monitoring of resistance to new and repurposed medicines;
  11. exploring methods to ensure treatment adherence;
  12. exploring regimen composition when the new generation of component medicines are available; and
  13. exploring the efficacy of other 6-month regimens.

50 A lineage effect is observed for lineage 1 strains that are shown to exhibit higher MICs than other lineages in vitro. The in vivo clinical significance of such an effect is unknown (

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