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An internationally generalizable risk index for mortality after one year of antiretroviral therapy

Tate, Janet P.; Justice, Amy C.; Hughes, Michael D.; Bonnet, Fabrice; Reiss, Peter; Mocroft, Amanda; Nattermann, Jacob; Lampe, Fiona C.; Bucher, Heiner C.; Sterling, Timothy R.; Crane, Heidi M.; Kitahata, Mari M.; May, Margaret; Sterne, Jonathan A.C.

doi: 10.1097/QAD.0b013e32835b8c7f
Clinical Science

Objective: Despite the success of antiretroviral therapy (ART), excess mortality continues for those with HIV infection. A comprehensive approach to risk assessment, addressing multiorgan system injury on ART, is needed. We sought to develop and validate a practical and generalizable mortality risk index for HIV-infected individuals on ART.

Design and methods: The Veterans Aging Cohort Study (VACS) was used to develop the VACS Index, based on age, CD4 cell count, HIV-1 RNA, hemoglobin, aspartate and alanine transaminase, platelets, creatinine and hepatitis C status, and a Restricted Index based on age, CD4 cell count and HIV-1 RNA with an outcome of death up to 6 years after ART initiation. Validation was in six independent cohorts participating in the ART Cohort Collaboration (ART-CC).

Results: In both the development (4932 patients, 656 deaths) and validation cohorts (3146 patients, 86 deaths) the VACS Index had better discrimination than the Restricted Index (c-statistics 0.78 and 0.72 in VACS, 0.82 and 0.78 in ART-CC). The VACS Index also demonstrated better discrimination than the Restricted Index for HIV deaths and non-HIV deaths, in men and women, those younger and older than 50 years, with and without detectable HIV-1 RNA, and with or without HCV coinfection.

Conclusions: Among HIV-infected patients treated with ART, the VACS Index more accurately discriminates mortality risk than traditional HIV markers and age alone. By accounting for multiorgan system injury, the VACS Index may prove a useful tool in clinical care and research.

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aYale University School of Medicine and the Veterans Affairs Healthcare System, West Haven, Connecticut

bDepartment of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA

cUniversité Bordeaux, ISPED, Centre Inserm U897- Epidemiologie-Biostatistique, Bordeaux, France

dDivision of Infectious Diseases and Department of Global Health, Amsterdam Institute for Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

eResearch Department of Infection and Population Health, UCL Medical School, London, UK

fDepartment of Internal Medicine, University of Bonn, Germany

gBasel Institute for Clinical Epidemiology & Biostatistics, University Hospital Basel, Basel, Switzerland

hDepartment of Medicine, Vanderbilt University, Nashville, Tennessee

iClinical Epidemiology and Health Services Research Core, Center for AIDS Research

jDepartment of Medicine, University of Washington, Seattle, Washington, USA

kDepartment of Social Medicine, University of Bristol, Bristol, UK.

Correspondence to Janet P. Tate, ScD, VA Connecticut Health Systems, 950 Campbell Avenue, West Haven, CT 06516, USA. Tel: +1 203 932 5711 X 5371; fax: +1 203 937 4926; e-mail:

Received 21 June, 2012

Revised 10 October, 2012

Accepted 16 October, 2012

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