CD4 Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy

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Abstract
Opportunistic infections (OIs) are an important cause of morbidity and mortality in children infected with HIV. However, few data are available regarding the overall prevalence, incidence and immunologic correlates associated with these diseases in the pediatric HIV population. The Pediatric AIDS Clinical Trials Group (PACTG) has conducted multicenter studies in HIV-infected children since 1988 and through these studies has collected prospective data on the immunologic and virologic status of study participants and recorded complications, including infectious diseases, related to HIV infection and its treatments. Therefore data were analyzed from across 13 PACTG studies, performed before treatment with highly active antiretroviral therapy was given, to determine the rates of various infectious complications and the immunologic correlates, specifically CD4 cell counts, associated with these diseases. OIs were tabulated from 3331 HIV-infected children who participated in 13 clinic trials undertaken before highly effective antiretroviral therapy was available. Five OIs occurred at event rates of >1.0 per 100 patient years (person years): serious bacterial infections, 15.1; herpes zoster, 2.9; disseminated Mycobacterium avium complex (DMAC), 1.8;Pneumocystis carinii pneumonia, 1.3; and tracheobronchial and esophageal candidiasis, 1.2. Six other OIs evaluated, cytomegalovirus (CMV) disease, cryptosporidiosis, tuberculosis, systemic fungal infections, toxoplasmosis and progressive multifocal leukoencephalopathy, occurred at event rates of <1.0 per 100 person years. Pneumonia (11.1 per 100 person years) and bacteremia (3.3 per 100 person years) were the most common bacterial infections. An AIDS-defining OI before entry was a risk factor for the development of a new OI during a trial. Bacterial infections, herpes zoster and tuberculosis occurred frequently at all stages of HIV infection; whereas DMAC, P. carinii pneumonia, CMV and other OIs occurred primarily in children with severe immunosuppression. The frequency of OIs in HIV-infected children in the pre-highly active antiretroviral therapy era varies with age, pathogen, prior OI and immunologic status. Analysis of CD4 counts at the time of DMAC, CMV and PCP provide validation for current prophylaxis guidelines in children ≥2 years old. This information on infectious complications of pediatric HIV will be especially valuable for contemporary management of HIV infection that is poorly responsive to highly active antiretroviral therapy.

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