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. Towards a combined prognostic index for survival in HIV infection: the role of non-HIV biomarkers.
Open accessAbstract
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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“It includes HIV-1 RNA, CD4 count, hepatitis C co-infection, FIB 4, eGFR, anemia, and age and is substantially more predictive of all causes of mortality than an index restricted to HIV-1 RNA, CD4 count, and age.”
From HIV and Aging: State of Knowledge and Areas of Critical Need for Research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group (2012) · cites this paper as [55]
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“However, eGFR can be readily obtained from standard blood chemistry panels and is an important component in multi-variate models of mortality and hospitalization in HIV-infected persons (15, 17, 48, 55).”
From HIV and Aging: State of Knowledge and Areas of Critical Need for Research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group (2012) · cites this paper as [55]
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Metadata
- Authors
- Justice, A., McGinnis, K., Skanderson, M., Chang, C., Gibert, C., Goetz, M., Rimland, D., Rodriguez‐Barradas, M., Oursler, K., Brown, S., Braithwaite, R., May, M., Covinsky, K., Roberts, M., Fultz, S., Bryant, K., & for the VACS Project Team
- Affiliations
- University of Pittsburgh (US)
- VA Pittsburgh Healthcare System (US)
- George Washington University (US)
- Emory University (US)
- Michael E. DeBakey VA Medical Center (US)
- University of Maryland, Baltimore (US)
- James J. Peters VA Medical Center (US)
- University of Bristol (GB)
- San Francisco VA Medical Center (US)
- United States Department of Veterans Affairs (US)
- VA Connecticut Healthcare System (US)
- ORCID
- Venue
- HIV Medicine
- Publisher
- Wiley
- Published
- 2010-01-04
- Volume
- 11
- Issue
- 2
- Pages
- 143-151
- ISSN
- 1464-2662 (ISSN-L)
- 1468-1293
- PMC
- PMC3077949
- OpenAlex
- W2007359807
- Cited by
- 159
- References
- 53
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 10 · 2017: 11 · 2016: 18 · 2015: 19 · 2014: 10 · 2013: 25 · 2012: 15
- FWCI
- 10.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- HIV Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (U10AA013566, 2U10 AA13566)
- National Institute on Aging (K23AG024896)
- Topics
- Health Sciences › Medicine › Infectious Diseases › HIV-related health complications and treatments
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Keywords
- HIV infection, prognostic score, mortality risk, highly active antiretroviral therapy, veterans, all-cause mortality, CD4 count, HIV RNA, chronic inflammation, substance abuse, risk stratification
- MeSH terms
- Aged, Anemia, Cause of Death, Drug Therapy, Combination, Female, Hepatitis, Viral, Human, Humans, Liver Cirrhosis, Male, Middle Aged, RNA, Viral, Severity of Illness Index, Cohort Studies, Biomarkers, HIV Infections, Confidence Intervals, Survival Analysis, AIDS-Related Opportunistic Infections, Disease Progression, CD4 Lymphocyte Count, Anti-HIV Agents, Substance-Related Disorders, HIV Long-Term Survivors
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