title: Severe manifestations of extrapulmonary tuberculosis in HIV-infected children initiating antiretroviral therapy before 2 years of age.
abstract: 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.
authors.affiliation: Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Stellenbosch University, Cape Town, South Africa.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Walters
authors.affiliation: Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Stellenbosch University, Cape Town, South Africa.
authors.forename: Joanie
authors.initials: J
authors.lastname: Duvenhage
authors.affiliation: Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Stellenbosch University, Cape Town, South Africa.
authors.forename: Heather R
authors.initials: HR
authors.lastname: Draper
authors.affiliation: Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Stellenbosch University, Cape Town, South Africa.
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Hesseling
authors.affiliation: Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Stellenbosch University, Cape Town, South Africa.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Van Wyk
authors.affiliation: Department of Paediatrics and Child Health, Tygerberg Academic Hospital, Stellenbosch University, Cape Town, South Africa.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
authors.affiliation: Department of Paediatrics and Child Health, Tygerberg Academic Hospital, Stellenbosch University, Cape Town, South Africa.
authors.forename: Helena
authors.initials: H
authors.lastname: Rabie
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D014376:Tuberculosis / Q000175:diagnosis*
keywords: Antiretroviral Therapy; HIV; Infants; Tuberculosis