Objectives:

To determine the incidence, clinical manifestations and risk factors for immune reconstitution inflammatory syndrome (IRIS) in young children initiating highly active antiretroviral therapy (HAART).

Design:

A prospective cohort of antiretroviral-naïve HIV-infected children less than 24 months of age enrolled in a treatment strategies trial in Johannesburg, South Africa.

Methods:

Among 169 HIV-infected children initiating HAART, April 2005 to November 2006, the records of 83 children suspected to have IRIS within 6 months of starting treatment were reviewed to determine whether they met criteria for IRIS. Seven were excluded due to incomplete follow-up. Pretreatment and post-treatment characteristics of children with and without IRIS were compared.

Results:

Overall, 34/162 (21%) children developed IRIS at a median of 16 days (range 7–115 days) post-HAART initiation. Bacille Calmette-Guérin reaction was most common occurring in 24/34 (71%) children, primarily injection site lesions and/or ipsilateral axillary lymphadenitis with abscess. Other IRIS conditions (not mutually exclusive) included Mycobacterium tuberculosis (n= 12), cytomegalovirus pneumonia (n= 1), Streptococcus pneumonia sepsis (n= 1), and severe seborrheic dermatitis (n= 1). Children with IRIS were younger (median age 7 vs. 10 months, P= 0.007) with a lower CD4 cell percentage (median 13.9 vs. 19.2, P= 0.009) at HAART initiation than controls. After 24 weeks on HAART, 62% of IRIS cases vs. 28% of controls had HIV RNA more than 400 copies/ml (P= 0.001), odds ratio= 2.88 (95% confidence interval= 1.14–7.29) after adjusting for baseline factors.

Conclusion:

Infants and young children with advanced HIV disease initiating HAART are at high risk for developing IRIS, leading to additional morbidity and possibly impairing virologic response to antiretroviral treatment.