Effects of negative life events on immune suppression in children and youth infected with human immunodeficiency virus type 1

Objectives. To evaluate the association of negative stressful life events experienced over 12 months and the risk of moderate to severe immune suppression among children and youth infected with human immunodeficiency virus type 1 (HIV-1). Methods. Longitudinal study of 618 HIV-1-infected children, baseline ages 1 to 20 years (mean age: 6.4 years), who completed 52 weeks of participation in the Pediatric Late Outcomes Study (Pediatric AIDS Clinical Trials Group Protocol 219). Severity of immune suppression was indicated by the Centers for Disease Control and Prevention Pediatric HIV Disease Classification System, based on CD4 percentages. The total number of negative life events-categorized as none, 1, or >1 life event reported as having occurred in the previous 12 months (previous 6 months for children <3 years of age)-was the predictor variable. Multiple logistic regressions were estimated to assess the relationship of negative life events and immune suppression at outcome, controlling for baseline measures of immune suppression, continuous CD4%, negative life events, age, race/ethnicity, gender, primary caretaker, education level of caretaker, and acquired immunodeficiency syndrome status. Results. At week 52, 379 subjects (61% of total study population) had moderate to severe immune suppression. Of 275 children with normal immune function at baseline, 68 (24.7%) subsequently developed moderate to severe suppression levels by week 52 of follow-up. Of 343 children with immune suppression at baseline, 32 (9.2%) had recovered to normal CD4% levels by week 52. More than 1 negative life event was associated with an increased risk (prevalence) of immune suppression (odds ratio [OR]: 2.76; 95% confidence interval [CI]: 1.44,5.31), controlling for baseline CD4%, total life events, and other covariates. Children without immune suppression at baseline who experienced >1 negative life event had an increased incidence of immune suppression (OR: 2.93; 95% CI: 1.34,6.39), controlling for baseline covariates. Conclusions. Results indicate that negative stressful life events increase the risk of children with HIV-1 infection having impaired immune function. Further research is needed to identify potential mechanisms of the relationship between stressful life events and impaired immune function. These mechanisms include psychoneuroendocrinologic response and difficulties in adherence to therapy after exposure of a child to major negative life events.