Immune reconstitution inflammatory syndrome among HIV-infected South African infants initiating antiretroviral therapy.

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-naive 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-Guerin 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.