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Severe manifestations of extrapulmonary tuberculosis in HIV-infected children initiating antiretroviral therapy before 2 years of age
  1. Elisabetta Walters1,
  2. Joanie Duvenhage1,
  3. Heather R Draper1,
  4. Anneke C Hesseling1,
  5. Susan S Van Wyk1,
  6. Mark F Cotton2,
  7. Helena Rabie2
  1. 1Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Stellenbosch University, Cape Town, South Africa
  2. 2Department of Paediatrics and Child Health, Tygerberg Academic Hospital, Stellenbosch University, Cape Town, South Africa
  1. Correspondence to Dr Elisabetta Walters, Faculty of Medicine and Health Sciences, Desmond Tutu TB Centre, Stellenbosch University Tygerberg Campus, K-Floor, Clinical Building, Francie Van Zijl Drive, Tygerberg, Cape Town 7505, South Africa; ewal{at}


Background Early initiation of antiretroviral therapy (ART) in HIV-infected infants reduces mortality and opportunistic infections including tuberculosis (TB). However, young HIV-infected children remain at high risk of TB disease following mycobacterial infection. We document the spectrum of TB disease in HIV-infected children <2 years of age on ART.

Methods Retrospective cohort study; records of children <2 years of age initiating routine ART at Tygerberg Children's Hospital, Cape Town, January 2003–December 2010 were reviewed. Clinical data at ART initiation (baseline) and TB episodes after ART initiation, to June 2012, were recorded. TB immune reconstitution syndrome (TB-IRIS) and incident TB were defined as TB diagnosed within 3 months, and >3 months after, ART initiation respectively. Baseline characteristics were compared in children with TB-IRIS and those with incident TB.

Results In 494 children, median follow-up time on ART was 10.7 months. Fifty-five TB treatment episodes occurred after ART initiation: 23 (42%) TB-IRIS (incidence 21.9/100 person years (py)) and 32 (58%) incident TB (incidence 3.9/100 py). Children with TB-IRIS and those with incident TB had similar baseline characteristics. Eight of 10 cases of extrapulmonary TB were severe: 4 IRIS (2 meningitis, 1 disseminated, 1 pericarditis) and 4 incident cases (1 each miliary, meningitis, pericarditis and spinal). Fifty-one children (10%) died (mortality rate 5.96/100 py). Starting ART at <1 year of age approached significance as a risk factor for TB-IRIS (adjusted OR (AOR) 8.64, p=0.06); weight-for-age Z score <−2 predicted death (AOR 6.37, p<0.001).

Conclusions Severe TB manifestations were observed among young HIV-infected children on ART.

  • HIV
  • Antiretroviral Therapy
  • Infants
  • Tuberculosis

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