Immune Reconstitution Syndrome in HIV: Validating a Case Definition and Identifying Clinical Predictors in Persons Initiating Antiretroviral Therapy

• Published in: Clinical infectious diseases 2006-06, Vol.42 (11), p.1639-1646
• Main Authors: Robertson, Jaime, Meier, Matthew, Wall, Jennifer, Ying, Jun, Fichtenbaum, Carl J.
• Format: Article
• Language: English
• Subjects: Adult; AIDS; AIDS-Related Opportunistic Infections - complications; Anti-HIV Agents - adverse effects; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretrovirals; Antiviral agents; Biological and medical sciences; Carts; Case-Control Studies; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes; Diagnostic tests; Disease; Drug therapy; Female; Hemoglobins; Herpes zoster; HIV; HIV Infections - complications; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Immune system; Immune System Diseases - chemically induced; Immune System Diseases - diagnosis; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infections; Infectious diseases; Lymphocytes; Male; Medical sciences; Opportunistic infections; Patients; Pharmacology. Drug treatments; Retrospective Studies; Risk Factors; Sensitivity and Specificity; Tuberculosis; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/503903

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 ⩾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 ⩾4 (on a scale of 0.0 to 100.0), and 92.86% and 80.00%, respectively, for a score of ⩾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.