5.1.2. Subgroup considerations

Children with peripheral lymph node TB: Although the number of children with peripheral lymph node TB in the SHINE trial were small (N=19 in the 16-week arm and N=21 in the 24-week arm), there was no difference in the proportion of unfavourable outcomes between the two arms. The SHINE trial also found that 16 weeks of treatment was non-inferior compared to 24 weeks of treatment among children with both peripheral lymph node disease and pulmonar y disease (N=182 in the 16-week arm and N=171 in the 24-week arm). These results may provide reassurance to clinicians regarding a seemingly delayed clinical response to TB treatment, frequently seen in children with peripheral lymph node TB (where lymph nodes remain enlarged even after treatment).

Children and adolescents living with HIV infection (CALHIV): CALHIV were eligible for enrolment in the SHINE trial; 65 (11%) CALHIV were enrolled in the 16-week arm and 62 (10%) in the 24-week arm. 49% of CALHIV in the 16-week arm and 43% in the 24-week arm were on antiretroviral treatment at the time of enrolment. 20% of CALHIV in both arms had a CD4 count of less than 200 cells per mm3. 51% of CALHIV in the 16-week arm and 63% in the 24-week arm were classified as severe as per the WHO immunological classification for established HIV infection (59). In this subgroup, the 16-week regimen was non-inferior as compared to the 24-week regimen, although the 95% confidence interval for the risk difference was wide (risk difference -4.3, 95% CI -14.9 to 6.2).

In view of the limited evidence, clinicians may consider treating CALHIV with non-severe TB for 4 months, depending on the degree of immunosuppression and ART status, as well as the presence of other opportunistic infections. These children and adolescents will need to be monitored closely, especially at 4 months of treatment, and treatment extended to 6 months if there is insufficient progress.

Children with SAM: In the SHINE trial, SAM was defined as weight-for-height Z-score (WHZ) (60). Thirty children with SAM (5%) were included in the 16-week arm and 33 (5%) in the 24-week arm. No separate subgroup analysis was therefore conducted for children with SAM.

In view of the insufficient evidence on this subgroup, and as SAM is defined as a danger sign, children with SAM and non-severe TB should preferably receive 6 months of TB treatment.

Infants Infants Guidance for national tuberculosis programmes on the management of tuberculosis in children (second edition) (8). Treatment may require dose adjustment to reconcile the effect of age and possible toxicity in young infants. The decision to adjust doses should be taken by a clinician experienced in the management of paediatric TB.

Children treated for TB in the past two years: Given the increased risk of treatment failure and of drug resistance, children and adolescents treated in the preceding two years were not eligible for inclusion in the SHINE trial; they should be treated with the 6-month treatment regimen (2HRZ(E)/4HR).

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