Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in children

Pediatr Pulmonol. 2016 Feb;51(2):157-64. doi: 10.1002/ppul.23221. Epub 2015 Jun 14.

Abstract

Background: Paradoxical tuberculosis (TB)-associated Immune Reconstitution Inflammatory Syndrome (IRIS) is a common complication of combination antiretroviral treatment (cART) initiation in adults residing in resource-limited regions. Little is known about the burden and presentation of TB-IRIS in children initiating cART while receiving TB treatment.

Methods: Prospective cohort study of South African children initiating cART while on TB treatment. Children were assessed clinically and by chest x-ray before starting cART and at 2, 4, 6, and 12 weeks post cART initiation. All children who presented with any signs or symptoms suggestive of paradoxical TB-IRIS were classified according to the consensus adult TB-IRIS case definition developed by the International Network for Study of HIV-associated IRIS (INSHI) and reviewed by an independent expert panel.

Results: In 7 of the 104 children enrolled in the cohort, symptoms and/or clinical or radiological signs suggestive of paradoxical TB-IRIS developed after a median of 14 days of cART. In two of these cases, there was agreement between the INSHI case definition and the expert panel. In an additional 3 cases, the INSHI criteria were fulfilled but the expert panel made an alternative diagnosis of pneumonia (n = 2) and poor adherence to cART (n = 1).

Conclusions: The burden of paradoxical TB-IRIS in children with underlying TB initiating cART is low. Including response to antibiotic treatment for pneumonia as a criterion for an alternative diagnosis may improve the specificity of the INSHI case definition.

Keywords: Africa; HIV; IRIS; TB; antiretroviral treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • Antitubercular Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / adverse effects*
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / chemically induced*
  • Immune Reconstitution Inflammatory Syndrome / immunology
  • Infant
  • Infant, Newborn
  • Lopinavir / adverse effects
  • Male
  • Prospective Studies
  • Ritonavir / adverse effects
  • South Africa
  • Tuberculosis / drug therapy*
  • Tuberculosis / immunology
  • Tuberculosis, Lymph Node / drug therapy
  • Tuberculosis, Lymph Node / immunology
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / immunology

Substances

  • Antitubercular Agents
  • HIV Protease Inhibitors
  • Lopinavir
  • Ritonavir