Children living with HIV infection: Most studies in the review were restricted to HIV-negative children. HIV-positive children represented a small proportion of children with TBM overall, and all received the intervention regimen. In the three studies using the intervention regimen included in the evidence review, 11 children were identified as having HIV infection (of a total of 724 children). Therefore, it was not possible to undertake analyses stratified by HIV infection. An additional small study of 13 children from South Africa used an extended duration of the intervention regimen (i.e. 9 months of HRZEto). Therefore, the recommendation on the 6-month regimen does not apply to HIV-infected children who are diagnosed with TBM.
Adolescents: The population in the PICO question included both children (aged 0-9 years) and adolescents (aged 10-19 years). Based on the available information in the studies the median age of patients in the three studies using the intervention regimen were: 35 months (range: 2 months-14 years), 28 months (range: 2 months-15 years) and 30 months (5-82 months). In the studies using the comparator regimen, the age structure reported in two of the three studies was:
Other subgroup analyses: Several subgroup analyses were pre-planned by the systematic reviewers (including subgroup analyses by: age group, for patients with DR-TB (including isoniazid-resistant TB), for patients who were microbiologically confirmed versus those clinically diagnosed, by Medical Research Council stage at diagnosis, and for patients with complications including tuberculoma and hydrocephalus). However, these analyses could not be conducted due to insufficient data.