RetourData from Study 31 allowed subgroup analyses for four patient groups: People with HIV, people with diabetes, people with a low body weight (i.e. a body mass index [BMI] <17.9 kg/m² ) and patients with extensive pulmonary TB disease (using a cut-off of > 50% lung parenchyma affected) on CXR. Although no statistically significant differences appeared when comparing the 4-month regimen to the current standard 2HRZE/4HR regimen, the number of patients in some of these subgroups was small (1).
Additional pharmacokinetic analyses being undertaken by the trial investigators will be available in the future and may provide additional information on drug exposures in these groups. Other subgroup analyses conducted as part of the trial included analyses by age group, sex, presence of cavities, cavity size, sputum smear grade, smoking history, Xpert® cycle threshold values and time to positivity (days) with the mycobacterial growth indicator tube (MGIT) liquid culture automated system.
4.4.1 Subgroups in which the shorter regimen can be used
The shorter regimen can be used in People with HIV, people with diabetes (although the evidence is modest), people with extensive pulmonary TB disease, and children and adolescents (1).
People with HIV
Study 31 included a sufficient proportion of People with HIV (about 8%), most of whom were on ART. Thus, sufficient evidence is available to support the use of the regimen when the CD4 count is not below 100 cells/mm³.
People with diabetes
There are scant data on the use of this regimen among people with diabetes, but additional information from pharmacokinetic analysis will become available in the future. Thus, although the shorter regimen may be considered as an option, it may be prudent to monitor this patient group closely for hepatotoxicity, and eventually consider therapeutic drug monitoring whenever feasible, if malabsorption is suspected (because of Diabetes or interactions with hypoglycaemic drugs). More information on the regimen’s effectiveness in this group will also be important because diabetes is common in some countries. Additional information on the management of patients with liver problems is given in Section 8.
People with extensive pulmonary TB disease
The trial reported on the presence of cavitation and the extent of disease on CXR, as a percentage and cavity size (absent, <4 cm or ≥4 cm). For some subgroups, there was limited or no evidence on the use of the shorter regimen, but the use of this shorter regimen could be considered because favourable outcomes were reported using it in patients with extensive pulmonary disease.
Children and adolescents
The 4-month regimen including rifapentine and moxifloxacin (2HPMZ/2HPM) may be selected for adolescents aged 12 years and over and weighing at least 40 kg with pulmonary TB, regardless of disease severity (30). Factors to consider before selecting this regimen are that:
- the regimen should not be used in children and adolescents aged under 12 years; and
- the regimen should not be used in adolescents with forms of extrapulmonary TB such as tuberculous meningitis, disseminated (miliary) TB, osteoarticular TB or abdominal TB.
4.4.2 Subgroups in which the regimen is not recommended
For some subgroups, there was no evidence (because they were ineligible for inclusion in the trial). The use of the shorter regimen outside of the research environment is not indicated in the subgroups giving below
Patients weighing less than 40 kg
Low body weight can indicate severe forms of TB disease; therefore, close follow-up and use of the 6-month regimen may be preferable in this subgroup, as there is more experience with this regimen
Patients with extrapulmonary TB
In patients with extrapulmonary TB – such as tuberculous meningitis, disseminated (miliary) TB, osteoarticular TB and abdominal TB – the regimen is not recommended.
People with HIV with a CD4 count of less than 100 cells/mm³
A low CD4 count is indicative of severe immunosuppression, leading to concerns about an increased risk of relapse in this group.
Children and adolescents aged under 12 years
There is presently no evidence on the use of this regimen in children and adolescents aged under 12 years.
Pregnant, breastfeeding and postpartum women
There is currently no evidence available on the use of this regimen in women who are pregnant, breastfeeding or postpartum.