Sepsis predisposition in children with human immunodeficiency virus

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To review predisposition to sepsis in children infected with human immunodeficiency virus (HIV) in the era of highly active antiretroviral therapy (HAART). Summary of the literature with review by experts in the field. In industrialized regions, new diagnoses of vertically acquired HIV infection are falling due to perinatal interventions. Provision of HAART has resulted in an enlarging cohort of clinically stable HIV-infected children, with low viral loads and normal CD4 T-lymphocyte counts. Access to HAART in "developed" countries has markedly decreased the rate of progression to acquired immunodeficiency syndrome, the prevalence of organ-specific complications of HIV, the risk of recurrent sepsis, and the high early childhood mortality from HIV infection. There are currently no data on whether initiation of HAART during acute sepsis reduces short-term morbidity or mortality. Undiagnosed, antiretroviral-naive, HIV-infected infants still present sporadically with opportunistic infections such as Pneumocystis jiroveci and cytomegalovirus pneumonia. HIV-infected children have a greater burden of disease due to viral, bacterial, and fungal sepsis, and the case fatality rate for nonopportunistic infections may be greater than in non-HIV-infected children. In "developing" countries, with limited access to HAART, the natural history of HIV infection has altered very little, with the majority of infected children dying from either opportunistic or nonopportunistic disease before 3 yrs of age. Pediatric HIV infection is not a homogeneous condition in the era of HAART. Susceptibility to sepsis, morbidity, and mortality differ according to stage of disease, access to HAART, and virologic and immunologic response to treatment. These issues should be considered if HIV-infected children are to be enrolled and stratified in clinical trials.