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Distribution of age at death and effects of immunosuppression and ART duration vary according to cause of death in HIV-1 positive people
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Reported by Jules Levin
CROI 2012
Suzanne M. Ingle, John Gill, Michael Mugavero, Charlotte Lewden, Sophie Abgrall, Gerd Fatkenheuer, Peter Reiss, Margaret May, Jonathan A C Sterne, and Mike Saag for the Antiretroviral Therapy Cohort Collaboration (ART-CC)
ABSTRACT
Background: Cause-specific mortality in treated HIV-positive people is poorly understood. Specific causes are likely to have differential associations with age, HIV disease and ART toxicity.
Methods: 16 cohorts from Europe and N America contributed data on adult patients who were followed up from starting ART. Causes of death were independently classified by two clinicians, and disagreements resolved via panel discussion. Age distributions and median CD4 count (<6 months before death) of those who died were compared with those of all patients at end of follow up. Effects of ART duration on causes of death were assessed using Poisson regression models adjusted for age, gender, CD4 and viral load, and stratified by cohort.
Results: From 1996 to 2009, 4237/65121 (6.5%) patients died during 327535 person years follow-up. Of 3574 (84.4%) deaths that could be classified as due to a specific cause 1496 (41.9%) were classified as due to AIDS. Median age at death from non-AIDS malignancy (N=461), myocardial infarction (MI) (N=106) and stroke (N=54) was higher than for all patients, whereas the age distribution of those who died from AIDS, non-AIDS infection (N=314) and violence (suicide, overdose and injuries, N=349) was similar. Median (IQR) CD4 count prior to death from any cause was 154 (45- 344) cells/mm3, compared to 207 (109-410) for non-AIDS malignancy, 305 (188-486) for stroke, and 370 (248-622) for MI. Among survivors, the last CD4 count was 475 (317-662) cells/mm3. For those who died with latest CD4 count <350, 350-499 and ≥ 500 cells/mm3, the proportion of AIDS deaths decreased from 47.7% to 17.3% and 9.1% respectively. Rates of AIDS death decreased markedly with time on ART (adjusted rate ratio [aRR] 0.81 per year: 95% CI 0.79-0.83). By contrast, rates of death from non-AIDS malignancy (aRR 1.05: 1.01-1.09), stroke (1.13: 1.02-1.26) and MI (1.04: 0.96-1.12) increased. There was little evidence for increases in rates of liver-related death (aRR 1.00 per year: 95% CI 0.96-1.05), infection deaths (0.98: 0.94-1.02) or violent deaths (0.97: 0.93-1.01).
Conclusion: Non-AIDS mortality (in particular cancer and cardiovascular mortality) will be of increasing importance with increasing duration of ART.
Acknowledgements: The French Hospital Database on HIV (FHDH) ANRS CO4, The Aquitaine Cohort ANRS CO3 (France); The AIDS Therapy Evaluation project Netherlands (ATHENA) (Netherland); The Italian Cohort of Antiretroviral-Naive Patients (ICONA) (Italia); The Swiss HIV Cohort Study (SHCS) (Switzerland); the Koln/Bonn Cohort (Germany); the EuroSIDA study (20 countries in Europe and Argentina); the British Columbia Centre for Excellence in HIV/AIDS (HOMER) and the South Alberta Clinic (Canada); the Prvecto para la Informatizacion del Seguimiento Clinico-epidemiologico de la Infeccion por HIV y SIDA (PISCIS) and CoRIS Cohort (Spain), the 1917 clinic Cohort University of Alabama, the University of Washington HIV Cohort, the HIV Atlanta Veterans Affairs Cohort Study (HAVACS), the Vanderbilt-Meharry Center for AIDS Research (USA).
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