Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal.
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.
Mocroft
Amanda
A
Sterne
Jonathan A C
JA
Egger
Matthias
M
May
Margaret
M
Grabar
Sophie
S
Furrer
Hansjakob
H
Sabin
Caroline
C
Fatkenheuer
Gerd
G
Justice
Amy
A
Reiss
Peter
P
d'Arminio Monforte
Antonella
A
Gill
John
J
Hogg
Robert
R
Bonnet
Fabrice
F
Kitahata
Mari
M
Staszewski
Schlomo
S
Casabona
Jordi
J
Harris
Ross
R
Saag
Michael
M
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
D019380:Anti-HIV Agents