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.
Robertson
Jaime
J
Department of Internal Medicine, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0560, USA. roberj5@ucmail.uc.edu
Meier
Matthew
M
Wall
Jennifer
J
Ying
Jun
J
Fichtenbaum
Carl J
CJ
D017088:AIDS-Related Opportunistic Infections / Q000150:complications; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006454:Hemoglobins; D006801:Humans; D007154:Immune System Diseases / Q000139:chemically induced* / Q000175:diagnosis; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity
D019380:Anti-HIV Agents; D006454:Hemoglobins