Drug-resistant tuberculosis treatment

4.5 Implementation considerations
Given the paucity of evidence on the use of BPaL, and the concerns mentioned above, members of 
the GDG suggested that it should be implemented only in the context of operational research. The 
GDG emphasized that, despite the promising treatment success rates observed in the Nix-TB study, the 
regimen may not be considered for programmatic use worldwide until additional evidence on efficacy 
and safety has been generated. The group emphasized the need for this research to take the form of 
RCTs as well as observational studies. Given the conditionality of this recommendation in the context 
of additional research, certain standards and principles are prerequisites for the implementation of 
BPaL. Further, the GDG emphasized that the principles of good clinical practice should apply in any 
operational research study involving
BPaL.
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These permitted antiretroviral treatments were: 1. nevirapine in combination with any nucleoside reverse transcriptase inhibitors (NRTIs), 
2. lopinavir/ritonavir in combination with any NRTIs, 3. tenofovir/lamivudine/abacavir (if normal renal function), 4. triple NRTI therapy
consisting of zidovudine, lamivudine and abacavir (however, noting the increased risk of peripheral nerve toxicity with zidovudine and 
linezolid), and 5. raltegravir in combination with
NRTIs.
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Usually this group of patients would include those with an extensive drug-resistance profile who have very limited treatment options 
as part of a longer treatment regimen. 

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Recommendations 
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Patient selection. Overall, to reproduce the treatment success rates observed in the Nix-TB study, all 
efforts need to be made to carefully select eligible patients. Once those patients are enrolled, it is also 
important to provide effective patient support to enable adherence to treatment, and close monitoring 
for adverse events, response to treatment and emerging drug resistance. As outlined below, all efforts 
should be made to ensure proper patient inclusion; obtain signed patient informed consent; administer 
treatment under closely monitored conditions; and ensure active pharmacovigilance and proper 
management of adverse drug reactions, and prevention of complications from drug–drug
interactions.
Ensure proper patient inclusion – use is not advised in pregnant and lactating women and in children, 
and the Nix-TB study gives other inclusion and exclusion criteria. Although DST is an important 
component of patient selection for the BPaL regimen (described below), another key implementation 
consideration is prior TB treatment history. Patients are eligible for the BPaL regimen if they have not 
received bedaquiline or linezolid for 2 weeks or more previously, and this was an eligibility criterion 
of the Nix-TB study. Given that the current WHO recommendation for longer treatment regimens for 
MDR/RR-TB includes bedaquiline and linezolid as priority medicines in Group A, some patients who 
have previously started treatment on a longer MDR/RR-TB regimen may in fact be ineligible for BPaL 
should they later develop fluoroquinolone resistance. This reaffirms WHO’s previous statements on 
the need to carefully select eligible patients for longer or shorter MDR/RR-TB treatment regimens, 
and once patients are receiving a regimen, to ensure patient support and close monitoring and 
follow-up, including monitoring for treatment failure and relapse, and emerging drug resistance, with 
DST performed when indicated. If resistance is suspected during treatment and DST is not available, 
the strains should be conserved and referred to a WHO SRL for further testing. Each operational 
research protocol on the use of BPaL in a given setting will need to include detailed inclusion and 
exclusion criteria.