Incidence, Spectrum and Outcome of Immune Reconstitution Syndrome in HIV-infected Children after Initiation of Antiretroviral Therapy

Background: Immune reconstitution syndrome (IRS) is a relatively common complication in HIV-infected adults starting combination antiretroviral therapy (cART). Data on IRS in HIV-infected children remain limited and are largely restricted to resource-limited settings. This study investigated the incidence, spectrum and outcome of IRS in a pediatric cohort in the United Kingdom. Methods: Retrospective analysis of clinical events during the first 12 months after initiation of cART in 135 treatment-na ve, HIV-infected children in the United Kingdom over a 5-year period. Demographic and laboratory data were provided by the Collaborative HIV Paediatric Study. Results: The median age at cART initiation was 6.6 years (interquartile range: 2.3-10.2). The median CD4 lymphocyte percentage (CD4%) at baseline was 15% (median CD4 lymphocyte count: 390 cells/mu L). Eight patients (5.9%) developed IRS (incidence: 5.7/100 person years). The IRS events comprised: Bacillus Calmette-Guerin-related complications (local ulceration/lymphadenitis; n = 4), pulmonary tuberculosis (n = 1), Mycobacterium avium intracellulare infection (n = 1), combined tuberculosis/Mycobacterium avium intracellulare infection (n = 1) and cutaneous herpes simplex (n = 1). The mortality was significantly higher in children with IRS than in those without (P < 0.0001). The only statistically significant risk factor for IRS identified was increment in CD4 count at 12 months after starting cART (P = 0.03). Conclusions: The incidence of IRS was significantly lower than previously reported from resource-limited settings, likely reflecting less profound immunodeficiency at cART initiation and fewer coexisting opportunistic infections in our cohort. However, IRS events were associated with considerable morbidity and mortality. Therefore, preventive strategies that can reduce the risk of IRS in children need to be identified.