Drug-resistant tuberculosis treatment

NEW RECOMMENDATION

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Recommendations 
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cohort of XDR-TB patients who started treatment in 2016 (and for whom treatment outcomes were 
available in 2018), only 39% completed treatment successfully, while 26% died, treatment failed for 
18% and an additional 17% were lost to follow-up or were not evaluated (1). 
Evidence base and analyses. The pressing need for more effective treatment regimens for patients 
with extensive drug resistance, including fluoroquinolone resistance and more extensive drug-resistance 
profiles, has been the driver for a number of studies and initiatives to test more effective and novel 
treatment regimens, including newer and repurposed medicines. One such study is the Nix-TB study, 
conducted by TB Alliance. The Nix-TB study was a one-arm, Phase III, open-label observational cohort 
study that assessed the safety, efficacy, tolerability and pharmacokinetic properties of a 6-month BPaL 
treatment regimen, extendable to 9 months for those who missed doses, or who remained culture 
positive or reverted from culture negative to positive between months 4 and 6 of treatment (89). The 
study was conducted between 2014 and 2019 at three study sites, all in South Africa, with the first 
patient enrolled in April 2015. Eligible patients were aged 14 years and above, weighed at least 35 kg, 
had a documented HIV result and had bacteriologically confirmed sputum culture positive XDR-TB or 
bacteriologically confirmed MDR/RR-TB, but were treatment intolerant or non-responsive to previous 
MDR/RR-TB treatment. A number of other inclusion criteria were applied (Box 2).
The Nix-TB study’s inclusion criteria were as follows: 
1. Provide written, informed consent prior to all trial-related procedures (if under 18, 
include consent of legal
guardian).
2. Body weight of ≥35 kg (in light clothing and no
shoes).
3. Willingness and ability to attend scheduled follow-up visits and undergo study 
assessments. 
4. Provide consent to HIV testing (if an HIV test was performed within 1 month prior 
to trial start, it should not be repeated as long as documentation can be provided 
[ELISA and/or Western Blot]). If HIV status is a confirmed known positive, repeated 
HIV test is not needed provided documentation is
available.
5. Male or female, aged 14 years or
above.
6. Subjects with one of the following pulmonary TB conditions: 
a. XDR-TB with i. documented culture positive (for 
M. tuberculosis) results within 
3 months prior to screening or 
M. tuberculosis confirmed in sputum based on 
molecular test within 3 months prior to or at screening; ii. documented resistance 
to isoniazid, rifamycins, a fluoroquinolone and an injectable historically at any 
time or at
screening.
b. MDR-TB documented by culture positive results (for 
M. tuberculosis.) within 
3 months prior to or at screening with documented non-response to treatment 
with the best available regimen for 6 months or more prior to enrolment who 
in the opinion of the investigator have been adherent to treatment and will be 
adherent to study regimen. 
c. MDR-TB documented by culture positive (for 
M. tuberculosis) results within 
3 months prior to or at screening who are unable to continue second-line drug 
regimen due to a documented intolerance to: i. 
p-aminosalicylic acid, ethionamide, 
aminoglycosides or fluoroquinolones; ii. current treatment not listed above that 
renders subject eligible for the study in the investigator’s
opinion.