. 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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The VACS Index is substantially more predictive of all causes of mortality than an index restricted to HIV-1 RNA, CD4 count, and age.
“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]
eGFR is an important component in multi-variate models of mortality and hospitalization in HIV-infected persons.
“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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Faces of Frailty in Aging with HIV Infection
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Patient-Reported Symptoms on the Antiretroviral Regimen Efavirenz/Emtricitabine/Tenofovir
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Frailty in People Living with HIV
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Heavy Alcohol Use and Age Effects on HIV‐Associated Neurocognitive Function
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Characteristics and Outcomes of HIV-Infected Patients With Severe Sepsis
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Physical Activity Intensity is Associated with Symptom Distress in the CNICS Cohort
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Physical Function and Frailty Tools in Mortality Prediction of Middle-Aged Adults With HIV
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Preventive cancer screening practices in HIV-positive patients
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A novel symptom cluster analysis among ambulatory HIV/AIDS patients in Uganda
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Brown, S. T., Tate, J. P., Kyriakides, T. C., Kirkwood, K. A., Holodniy, M., Goulet, J. L., Angus, B., Cameron, D. W., Justice, A. C., & for the OPTIMA Team (2014) · PLoS ONE · doi:10.1371/journal.pone.0092606 · Cited by 21 · see citing works
Antoniou, T., Ng, R., Glazier, R. H., Kopp, A., & Austin, P. C. (2014) · Annals of Epidemiology · doi:10.1016/j.annepidem.2014.04.002 · Cited by 21 · see citing works
The Silent Epidemic - Frailty and Aging with HIV.
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Association of the Veterans Aging Cohort Study Index with Exercise Capacity in HIV-Infected Adults
Oursler, K. K., Tate, J. P., Gill, T. M., Crothers, K. A., Brown, T. T., Crystal, S., Womack, J. A., Leaf, D. A., Sorkin, J. D., & Justice, A. C. (2013) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2012.0388 · Cited by 20 · see citing works
Inceer, M., Brouillette, M.-J., Fellows, L. K., Morais, J., Harris, M., Smaill, F., Smith, G. H. R., Thomas, R., & Mayo, N. E. (2022) · HIV Medicine · doi:10.1111/hiv.13236 · Cited by 19 · see citing works
Gnatienko, N., Freiberg, M., Blokhina, E., Yaroslavtseva, T., Bridden, C., Cheng, D., Chaisson, C. E., Lioznov, D., Bendiks, S., Koerbel, G., et al. (2018) · HIV Clinical Trials · doi:10.1080/15284336.2018.1459344 · Cited by 16 · see citing works
Incidence, Timing, and Determinants of Bacterial Pneumonia Among HIV-Infected Patients
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The difficulties of classifying renal disease in HIV-infected patients*
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Incident Rheumatoid Arthritis in HIV Infection: Epidemiology and Treatment
Hanberg, J. S., Hsieh, E., Akgün, K. M., Weinstein, E. J., Fraenkel, L., Justice, A. C., & the VACS Project Team (2021) · Arthritis & Rheumatology · doi:10.1002/art.41802 · Cited by 15 · see citing works
Go, V. F.-L., Minh, N. L., Frangakis, C., Ha, T. V., Latkin, C. A., Sripaipan, T., Davis, W., Zelaya, C. E., Ngoc, N. P., & Quan, V. M. (2013) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2012.12.003 · Cited by 14 · see citing works
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Haemoglobin and Anaemia in the Smart Study
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- 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 › Emergency Medicine › 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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