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August 2006

Risk Factors for Opportunistic Illnesses in Children With Human Immunodeficiency Virus in the Era of Highly Active Antiretroviral Therapy

Author Affiliations

Author Affiliations: Departments of Epidemiology (Drs Ylitalo and Seage) and Biostatistics (Dr Hughes) and Center for Biostatistics in AIDS Research (Dr Brogly), Harvard School of Public Health, Boston, Mass; Stony Brook Children's Service, Stony Brook University, New York, NY (Dr Nachman); Department of Pediatrics, Duke University Medical Center, Durham, NC (Dr Dankner); and Department of Pediatrics, Tulane School of Medicine, New Orleans, La (Dr Van Dyke).

Arch Pediatr Adolesc Med. 2006;160(8):778-787. doi:10.1001/archpedi.160.8.778

Objective  To examine the relationship between the use of highly active antiretroviral treatment (HAART) and the occurrence of opportunistic illnesses (OIs) among children perinatally infected with human immunodeficiency virus.

Design  Prospective cohort study.

Setting  Pediatric AIDS Clinical Trials Group 219C cohort.

Participants  From September 15, 2000, to August 31, 2003, 1927 children perinatally infected with human immunodeficiency virus and receiving HAART were followed up.

Main Exposures  Age at initiating HAART, duration of HAART use, CD4+ T-lymphocyte percentage, and human immunodeficiency virus 1 viral load.

Main Outcome Measures  Incidence rates for Centers for Disease Control and Prevention OI category B and OI category C events were calculated. The association between main exposures and OI occurrence was estimated using proportional hazards regression.

Results  Of 1927 subjects, 226 (12.7%) developed OIs during follow-up. Incidence rates were 4.99 per 100 person-years (95% confidence interval, 4.30-5.76) for first OI category B events and 1.47 per 100 person-years (95% confidence interval, 1.12-1.91) for first OI category C events. Duration of HAART use was not related to OI risk. Older age (age >10 years) at HAART initiation was associated with increased risk of a first OI (hazard ratio, 2.48; 95% confidence interval, 1.23-5.00) compared with initiating HAART in children younger than 2 years. This increased risk diminished after adjusting for CD4+ T-lymphocyte percentage and Centers for Disease Control and Prevention disease category at HAART initiation. More children with OIs than without OIs had a CD4+ T-lymphocyte percentage of less than 15% at HAART initiation (49.6% of children with OIs vs 23.7% of children without OIs), at enrollment (41.2% of children with OIs vs 7.7% of children without OIs), and at the end of follow-up (41.2% of children with OIs vs 8.3% of children without OIs).

Conclusions  Opportunistic illnesses are occurring in the pediatric human immunodeficiency virus population in the HAART era, mainly in children with persistently low CD4+ T-lymphocyte percentages. Lack of a sustained response to HAART rather than age at or duration of HAART use is predictive of OI risk.