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

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Abstract
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.