3.4 Subgroups

This 6-month regimen can be used in all subgroups, including PLHIV 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 PLHIV

The interactions of rifampicin (the mainstay of TB treatment) with antiretroviral therapy (ART) are of concern in HIV-associated TB. When the 6-month rifampicin-containing regimen is used, these drug interactions may result in decreased concentrations of antiretroviral drugs. Key considerations for managing concomitant TB and HIV therapy were published by WHO in 2016 (23). Standard, rifampicincontaining anti-TB treatment was recommended in combination with efavirenz-based ART. Conversely, key contraindicated drug combinations were rifampicin with nevirapine and protease inhibitors. In people with HIV-associated TB receiving these drugs, rifabutin (where available) was suggested as a suitable substitute for rifampicin.

Rifampicin is known to lower plasma concentrations of the HIV medication dolutegravir. This has led to concerns about efficacy and the development of HIV resistance due to lower levels of dolutegravir. In such cases, WHO guidelines recommend adjusting the dose by offering 50 mg of dolutegravir twice per day (instead of a single daily dose of 50 mg) (23). These recommendations are still in place, although evidence that doubling the dose of dolutegravir might not be necessary is emerging. A study from Botswana demonstrated the efficacy and safety of a standard dose dolutegravir-based regimen compatible with an efavirenz-based regimen for HIV-positive TB patients who received rifampicin (24).

3.4.2 Children

Children with suspected or confirmed pulmonary TB or tuberculous peripheral lymphadenitis who live in settings with a low prevalence of HIV or of isoniazid resistance, or children who are HIV-negative, can be treated with a three-drug regimen (HRZ) for 2 months followed by a two-drug regimen (HR) for 4 months at the dosages specified in Annex 1. Treatment may require dose adjustment to reconcile the effect of age and possible toxicity in infants (20).

The reduced pill burden afforded by using the recommended FDCs may be especially valuable in patients with comorbidities (notably HIV infection) and in paediatric patients (who may have some difficulty in swallowing a large quantity of medications). Therefore, the availability of palatable dispersible formulations specifically tailored to children is of paramount importance.

Patients with some specific medical conditions (e.g. intolerance to certain TB drugs, or impairment of liver or renal function) are likely to require individualized adjustment of medication dose; however, this can only be done with single drug formulations.

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