Immune reconstitution syndrome in HIV: validating a case definition and identifying clinical predictors in persons initiating antiretroviral therapy.

Background: Clinical deterioration after initiation of antiretroviral therapy may result from restored immunity. There is no standard clinical definition for immune reconstitution syndrome. The objectives of this study were to validate a proposed definition and to identify factors predictive of immune reconstitution syndrome.

Methods: This was a retrospective case-control study from an academic university medical practice. Cases were matched to > or =2 control subjects by CD4+ cell count at the time of initiation of antiretroviral therapy. Cases and "mock cases" were blindly reviewed by 2 human immunodeficiency virus (HIV) experts.

Results: Twenty possible cases of immune reconstitution syndrome were identified; HIV experts excluded all cases of herpes zoster (shingles), with agreement on real and mock cases of 92%. For 14 confirmed case patients (compared with 40 control subjects), immune reconstitution syndrome was associated with a higher number of prior opportunistic infections (P=.003) and higher CD8+ cell counts at baseline (P=.05) and at week 12 (P=.02). Immune reconstitution syndrome was associated with lower baseline levels of alanine aminotransferase (P=.05) and hemoglobin (P=.02). On multivariate analysis, the number of prior opportunistic infections (odds ratio, 2.7; P=.007) and lower hemoglobin level at baseline (odds ratio, 0.8; P=.003) were independently associated with development of immune reconstitution syndrome. A predictive model was defined by classification and regression tree analysis with a sensitivity and specificity of 78.57% and 87.50%, respectively, for an importance score of > or =4 (on a scale of 0.0 to 100.0), and 92.86% and 80.00%, respectively, for a score of > or =2, using the number of prior opportunistic infections, CD8+ cell count, and hemoglobin level.

Conclusions: A standard definition for immune reconstitution syndrome is possible. Patients with a greater severity of illness at initiation of antiretroviral therapy are at risk for immune reconstitution syndrome. The model defined by classification and regression tree analysis may provide a basis for risk stratification before initiation of antiretroviral therapy.