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Background Children with human immunodeficiency virus (HIV, CWH) are at high risk of tuberculosis (TB) and face poor outcomes, despite antiretroviral therapy (ART). We evaluated outcomes in CWH and children not living with HIV treated for nonsevere TB in the SHINE trial. Methods SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, nonsevere TB who were randomized to receive 4 versus 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CWH. Results Of 1204 children enrolled, 127 (11%) were CWH, of similar age (median, 3.6 years; interquartile range, 1.2, 10.3 versus 3.5 years; 1.5, 6.9; P =.07) but more underweight (weight-for-age z score, −2.3; (3.3, −0.8 versus −1.0; −1.8, −0.2; P <.01) and anemic (hemoglobin, 9.5 g/dL; 8.7, 10.9 versus 11.5 g/dL; 10.4, 12.3; P <.01) compared with children without HIV. A total of 68 (54%) CWH were ART-naive; baseline median CD4 count was 719 cells/mm3 (241–1134), and CD4% was 16% (10–26). CWH were more likely to be hospitalized (adjusted odds ratio, 2.4; 1.3–4.6) and to die (adjusted hazard ratio [aHR], 2.6; 95% confidence interval [CI], 1.2 to 5.8). HIV status, age <3 years (aHR, 6.3; 1.5, 27.3), malnutrition (aHR, 6.2; 2.4, 15.9), and hemoglobin <7 g/dL (aHR, 3.8; 1.3,11.5) independently predicted mortality. Among children with available viral load (VL), 45% and 61% CWH had VL <1000 copies/mL at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 versus 6 months) on TB treatment outcomes by HIV status (P for interaction = 0.42). Conclusions We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CWH treated for nonsevere TB. Irrespective of TB treatment duration, CWH had higher rates of mortality and hospitalization than their counterparts without HIV. Clinical Trials Registration.  ISRCTN63579542. [ABSTRACT FROM AUTHOR]

Background Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization–recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. Methods Children weighing 4.0–7.9, 8.0–11.9, 12.0–15.9, or 16.0–24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0–36.9 kg received doses recommended for adults <37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. Results In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4–6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1–45.1), 16.7 (9.2–25.9), 317 (263–399), and 9.5 (7.5–11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0–7.9-, 8–11.9-, and ≥25-kg weight bands, isoniazid in the 4.0–7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. Conclusions Recommended weight band–based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization–recommended doses requires further evaluation. [ABSTRACT FROM AUTHOR]