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The regimen evaluated by Study 31 comprised 8 weeks of daily isoniazid, rifapentine, moxifloxacin and pyrazinamide, followed by 9 weeks of daily isoniazid, rifapentine and moxifloxacin (2HPMZ/2HPM)
For this regimen, daily dosing (i.e. 7 days per week, as used in Study 31) is suggested, taking advantage of a treatment supporter or video-supported treatment (VST).
Adults and children aged 12 years or older with a body weight of more than 40 kg and affected by pulmonary DS-TB are eligible for this regimen, including those who are also HIV-positive with a CD4 count of more than 100 cells/mm³ and patients with diabetes. The following exceptions, detailed in Section 4.4.2, should be highlighted:
Three Phase III trials (i.e. REMoxTB, OFLOTUB and RIFAQUIN) failed to demonstrate non-inferiority of shorter regimens used to treat DS-TB (26-28). The recent Phase III trial Study 31 (1) assessed the safety and efficacy of two 4-month regimens for the treatment of DS-TB (29). Patients from 13 countries were recruited for this multicentre, open-label, three-arm non-inferiority RCT, which was carried out in adolescents and adults (aged ≥12 years) with smear and culture positive pulmonary DS-TB (29).
Standard treatment monitoring should be ensured to assess the treatment response and any adverse events.
The available tools for treatment monitoring are bacteriological examinations (sputum smear, culture and DST), chest radiography (CXR) and clinical examination by the treating physician.
The important timepoints of the necessary TB monitoring examinations are after 2 months of treatment (especially if the patient does not improve, and underlying drug-resistance and possible failure are suspected) and at the end of treatment.
This 6-month regimen can be used in all subgroups, including People with HIV and children. This regimen can also be used in patients with extrapulmonary TB, except those with TB affecting the central nervous system or with osteoarticular forms of TB.
3.4.1 People with HIV
The 6-month rifampicin-based regimen is the standard regimen for the treatment of DS-TB in many countries and has been for many years; thus, there is a great deal of experience in using this regimen.
Rapid diagnostic testing and universal DST is a recommended target for all NTPs (4). In settings where DST results are not yet routinely available to guide the management of individual patients, patient history and clinical judgement are used to make decisions on the empirical use of this regimen.
The WHO guidelines recommend treating people with DS-TB with a 6-month regimen composed of four first-line TB medicines: isoniazid, rifampicin, pyrazinamide and ethambutol (1). The regimen is a combination of those four drugs (i.e. HRZE) for 2 months followed by isoniazid and rifampicin (i.e. HR) for 4 months, administered daily.
Any patient – whether a child or an adult – with DS-TB is eligible for this regimen. The regimen is considered safe for pregnant women; it can also be used in children of all ages, although ethambutol can be omitted for patients who are HIV-negative or in settings with a low prevalence of HIV or isoniazid resistance. Patients without a history of TB disease and treatment are less likely to have strains resistant to first-line medicines, although infection by the resistant strains often cannot be ruled out, especially in resource-limited settings.
All patients with DS-TB without documented resistance to isoniazid and rifampicin may be treated using the 6-month rifampicin-containing regimen 2HRZ(E)/4HR, which comprises isoniazid, rifampicin, pyrazinamide and ethambutol, for 2 months followed by isoniazid and rifampicin for 4 months (1).
All treatment delivered should align with WHO-recommended standards, including patient-centred care and support, informed consent where necessary, principles of good clinical practice, and regular patient monitoring to assess regimen effectiveness and patient safety (1). Clinical monitoring of people on treatment is important, and this handbook includes information on both treatment monitoring and the usefulness of post-treatment follow-up for special cases (e.g. long-term complications of TB or TB sequelae).