The South African NTP implemented the 9-month all-oral MDR/RR-TB regimen as a standardized course of treatment, with little room for variation. Some changes to the prescribed regimen were considered acceptable in the South African context and may be appropriate in other settings (as described in Section 5.2).
Some patients who start treatment with the 9-month all-oral regimen are unable to continue or complete the course of treatment, and may have to restart or switch to a different regimen; for example, in the following situations:
- Reliable DST results indicate resistance to key medicines (i.e. bedaquiline, levofloxacin/moxifloxacin, linezolid/ethionamide or clofazimine) in the 9-month all-oral MDR/RR-TB regimen; this may reflect the actual situation at the start of treatment (that was unknown at that time) or the acquisition of additional resistance during treatment. This situation would be considered “treatment failure” and the patient should not continue the 9-month regimen. Other regimens may be considered based on relevant eligibility criteria.
- Poor response or lack of response to treatment (e.g. no sputum smear conversion from positive to negative by 6 months, persistent positive sputum cultures from month 4 (or month 6 if extended) and beyond, or clinical deterioration despite evidence of adherence to treatment). This situation would be considered “treatment failure” and other treatment options will need to be considered. A longer individualized regimen would be the most appropriate option to offer such patients; however, BPaLM may also be considered if all eligibility criteria are met.
- An adverse drug reaction that necessitates permanent withdrawal of any one of the key medicines (i.e. bedaquiline, levofloxacin/moxifloxacin, linezolid/ethionamide or clofazimine), or two or more of any of the remaining medicines included in the 9-month all-oral regimen. This situation would be considered “treatment failure” and the patient should not continue the 9-month regimen. Other regimens may be considered based on relevant eligibility criteria.
- Treatment interruption for at least 2 months after receiving treatment with the 9-month all-oral regimen for more than 1 month. If such patients return to care, they might still be eligible for the 9-month all-oral regimen again, or the BPaLM regimen, but it is likely that they will first have to start a longer regimen while awaiting results of DST to rule out acquired resistance to the key drugs in the respective regimens.
If the treatment interruption is for less than 2 months, it is up to the treating clinician to decide whether the 9-month all-oral MDR/RR-TB regimen may be continued from the point of interruption. This decision is based on the timing of the interruption (early or late in treatment), the reasons for interruption, the patient’s clinical condition and the results of safety investigations. It is preferable for the patient to make up any missed doses of linezolid and bedaquiline, but this may or may not be necessary for the other medicines in the 9-month all-oral regimen.