Towards a combined prognostic index for survival in HIV infection: the role of ‘non‐HIV’ biomarkers |
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| Authors: | AC Justice KA McGinnis M Skanderson CC Chang CL Gibert MB Goetz D Rimland MC Rodriguez‐Barradas KK Oursler ST Brown RS Braithwaite M May KE Covinsky MS Roberts SL Fultz KJ Bryant for the VACS Project Team |
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| Affiliation: | 1. Section of General Internal Medicine, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA;2. Yale University School of Medicine, New Haven, CT, USA;3. Center for Urban and Social Research, University of Pittsburgh, Pittsburgh, PA, USA;4. Center for Health Equity Research and Promotion, Pittsburgh VA Healthcare System, Pittsburgh, PA, USA;5. Section of Decision Sciences and Clinical Systems Modeling, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;6. George Washington University Medical Center, VA Medical Center, Washington, DC, USA;7. VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;8. VA Medical Center and Emory University School of Medicine, Atlanta, GA, USA;9. Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX, USA;10. Baltimore VA Medical Center, University of Maryland School of Medicine, Baltimore, MD, USA;11. James J. Peters VA Medical Center, Bronx, NY, USA;12. Mt. Sinai School of Medicine, New York, NY, USA;13. Department of Social Medicine, University of Bristol, Bristol, UK;14. University of California, San Francisco, CA, USA;15. San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA;16. US Department of Veterans Affairs, Veterans Health Administration, Office of Public Health and Environmental Hazards, Washington, DC, USA;17. National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA |
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| Abstract: | Background As those with HIV infection live longer, ‘non‐AIDS’ condition associated with immunodeficiency and chronic inflammation are more common. We ask whether ‘non‐HIV’ biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART). Methods Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV‐infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS‐defining conditions); ‘non‐HIV’ biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data. Results Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle‐aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and ‘non‐HIV’ markers were associated with each other (P<0.0001) and discriminated mortality (C statistics 0.68–0.73); when combined, discrimination improved (P<0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30‐day C statistic 0.86, 95% confidence interval (CI) 0.80–0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72–0.74). Results were robust to adjustment for missing data. Conclusions When added to HIV biomarkers, ‘non‐HIV’ biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research. |
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| Keywords: | anaemia CD4 cell count hepatitis C coinfection hepatology injecting drug use outcomes renal/kidney risk groups viral load |
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