title: Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal.
abstract: BACKGROUND
  The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy.
  
  
  METHODS
  We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a "rare ADEs" category.
  
  
  RESULTS
  During a median follow-up period of 43 months (interquartile range, 19-70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin's lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84-22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70-14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin's lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55-9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76-3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08-2.00]).
  
  
  CONCLUSIONS
  In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management.
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.forename: Jonathan A C
authors.initials: JA
authors.lastname: Sterne
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Margaret
authors.initials: M
authors.lastname: May
authors.forename: Sophie
authors.initials: S
authors.lastname: Grabar
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: Gerd
authors.initials: G
authors.lastname: Fatkenheuer
authors.forename: Amy
authors.initials: A
authors.lastname: Justice
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
authors.forename: John
authors.initials: J
authors.lastname: Gill
authors.forename: Robert
authors.initials: R
authors.lastname: Hogg
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bonnet
authors.forename: Mari
authors.initials: M
authors.lastname: Kitahata
authors.forename: Schlomo
authors.initials: S
authors.lastname: Staszewski
authors.forename: Jordi
authors.initials: J
authors.lastname: Casabona
authors.forename: Ross
authors.initials: R
authors.lastname: Harris
authors.forename: Michael
authors.initials: M
authors.lastname: Saag
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis / Q000401:mortality*; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000175:diagnosis / Q000401:mortality; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D019380:Anti-HIV Agents