Impact of risk factors for specific causes of death in the first and subsequent years of antiretroviral therapy among HIV-infected patients.
BACKGROUND
Patterns of cause-specific mortality in individuals infected with human immunodeficiency virus type 1 (HIV-1) are changing dramatically in the era of antiretroviral therapy (ART).


METHODS
Sixteen cohorts from Europe and North America contributed data on adult patients followed from the start of ART. Procedures for coding causes of death were standardized. Estimated hazard ratios (HRs) were adjusted for transmission risk group, sex, age, year of ART initiation, baseline CD4 count, viral load, and AIDS status, before and after the first year of ART.


RESULTS
A total of 4237 of 65 121 (6.5%) patients died (median, 4.5 years follow-up). Rates of AIDS death decreased substantially with time since starting ART, but mortality from non-AIDS malignancy increased (rate ratio, 1.04 per year; 95% confidence interval [CI], 1.0-1.1). Higher mortality in men than women during the first year of ART was mostly due to non-AIDS malignancy and liver-related deaths. Associations with age were strongest for cardiovascular disease, heart/vascular, and malignancy deaths. Patients with presumed transmission through injection drug use had higher rates of all causes of death, particularly for liver-related causes (HRs compared with men who have sex with men: 18.1 [95% CI, 6.2-52.7] during the first year of ART and 9.1 [95% CI, 5.8-14.2] thereafter). There was a persistent role of CD4 count at baseline and at 12 months in predicting AIDS, non-AIDS infection, and non-AIDS malignancy deaths. Lack of viral suppression on ART was associated with AIDS, non-AIDS infection, and other causes of death.


CONCLUSIONS
Better understanding of patterns of and risk factors for cause-specific mortality in the ART era can aid in development of appropriate care for HIV-infected individuals and inform guidelines for risk factor management.
School of Social and Community Medicine, University of Bristol, United Kingdom.
Suzanne M
SM
Ingle
School of Social and Community Medicine, University of Bristol, United Kingdom.
Margaret T
MT
May
Division of Infectious Diseases, University of Calgary, Canada.
M John
MJ
Gill
Division of Infectious Disease, Department of Medicine, University of Alabama, Birmingham.
Michael J
MJ
Mugavero
INSERM, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux Université Bordeaux, Institut de Santé Publique, d'Epidémiologie et de Developpement (ISPED).
Charlotte
C
Lewden
UPMC Université Paris 06, UMR_S 943 INSERM, UMR_S 943, Paris Service des maladies infectieuses et tropicales, AP-HP, Hôpital Avicenne, Bobigny, France.
Sophie
S
Abgrall
Department of Internal Medicine, University of Cologne, Germany.
Gerd
G
Fätkenheuer
Stichting HIV Monitoring, and Division of Infectious Diseases and Department of Global Health, Amsterdam Institute for Global Health and Development, Academic Medical Center, University of Amsterdam, The Netherlands.
Peter
P
Reiss
Division of Infectious Disease, Department of Medicine, University of Alabama, Birmingham.
Michael S
MS
Saag
Infectious Diseases Service, Hospital Clinic-IDIBAPS, Barcelona, Spain.
Christian
C
Manzardo
INSERM, UMR_S 943, Paris AP-HP, Hôpital Cochin, Unité de Biostatistique et Epidémiologie, Paris Université Paris Descartes.
Sophie
S
Grabar
INSERM, ISPED, Centre Inserm U897-Epidemiologie-Biostatistique, Bordeaux, France.
Mathias
M
Bruyand
BC Centre for Excellence in HIV/AIDS, Department of Medicine, University of British Columbia, Vancouver, Canada.
David
D
Moore
Research Department of Infection and Population Health, University College London, United Kingdom.
Amanda
A
Mocroft
Vanderbilt University School of Medicine, Nashville, Tennessee.
Timothy R
TR
Sterling
Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, University of Milan, Italy.
Antonella
A
D'Arminio Monforte
Red de Investigación en Sida, Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid CIBER de Epidemiología y Salud Pública, Madrid.
Victoria
V
Hernando
Unit of Infectious Diseases, Hospital Sierrallana, Torrelavega, Spain.
Ramon
R
Teira
HIV Atlanta VA Cohort Study, Atlanta Veterans Affairs Medical Center, Decatur, Georgia.
Jodie
J
Guest
Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Switzerland.
Matthias
M
Cavassini
Clinical Epidemiology and Health Services Research Core, Center for AIDS Research, University of Washington, Seattle.
Heidi M
HM
Crane
School of Social and Community Medicine, University of Bristol, United Kingdom.
Jonathan A C
JA
Sterne
D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D002423:Cause of Death; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D012307:Risk Factors; D055815:Young Adult
HIV; antiretroviral therapy; cause-specific mortality