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Incidence of Opportunistic Illness Before and After Initiation of Highly Active Antiretroviral Therapy in Children

Nesheim, Steven R. MD*†; Hardnett, Felicia MS; Wheeling, John T. MPH§; Siberry, George K. MD, MPH; Paul, Mary E. MD; Emmanuel, Patricia MD**; Bohannon, Beverly MS, RN; Dominguez, Kenneth MD, MPHfor the LEGACY Consortium

The Pediatric Infectious Disease Journal: October 2013 - Volume 32 - Issue 10 - p 1089–1095
doi: 10.1097/INF.0b013e31829ee893
HIV Reports

Background: Little is known about immune reconstitution inflammatory syndrome in children in the United States.

Methods: LEGACY is a longitudinal cohort study of HIV-infected participants 0–24 years at enrollment during 2005 to 2007 from 22 US clinics. For this analysis, we included participants with complete medical record abstraction from birth or time of HIV diagnosis through 2006. Opportunistic illness (OI) included AIDS-defining conditions and selected HIV-related diagnoses. We calculated the incidence (#/100 patient-years) of OI diagnosed in the months pre- and postinitiation of the first highly active antiretroviral therapy (HAART) regimen which was followed by ≥1 log reduction in HIV viral load. We defined OI as immune reconstitution inflammatory syndrome if an OI incidence increased after HAART initiation. “Responders” were defined as experiencing ≥1 log decline in viral load within 6 months after HAART initiation.

Results: Among 575 patients with complete chart abstraction, 524 received HAART. Of these 524 patients, 343 were responders, 181 were nonresponders and 86 experienced OI. Responders accounted for 98 of 124 (79%) of OI. Pre-HAART and post-HAART OI incidences were 43.7 and 24.4 (P = 0.003), respectively, among responders and 15.9 and 9.1 (P = 0.2), respectively, among nonresponders. Overall, OI incidences among responders and nonresponders were 33.8 and 12.3, respectively (P = 0.002). Responders were more likely than nonresponders to experience herpes simplex and herpes zoster before HAART initiation (all, P < 0.002).

Conclusions: The lack of immune reconstitution inflammatory syndrome in participants initiating HAART may be due to low overall OI rates. The unexpectedly higher OI prevalence comprised mainly of herpes simplex and zoster, before HAART initiation among responders, may have motivated them to better adhere to HAART.

Supplemental Digital Content is available in the text.

From the *Emory University School of Medicine; Epidemiology Branch, Quantitative Sciences and Informatics Branch, Division of HIV/AIDS Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention; §Northrop Grumman Inc., Atlanta, GA; Pediatric Adolescent Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD; Baylor College of Medicine, Houston, TX; and **University of South Florida School of Medicine, Tampa, FL.

Accepted for publication June 4, 2013.

The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

The LEGACY project was funded by the Centers for Disease Control and Prevention, Atlanta, GA, contract number 200-2004-09976.

The authors have no other funding or conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Address for correspondence: Steven R. Nesheim, MD, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333. E-mail:

© 2013 by Lippincott Williams & Wilkins, Inc.