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. 2010 Feb;11(2):143-51.
doi: 10.1111/j.1468-1293.2009.00757.x. Epub 2009 Sep 14.

Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers

Amy C Justice  1 , K A McGinnis, M Skanderson, C C Chang, C L Gibert, M B Goetz, D Rimland, M C Rodriguez-Barradas, K K Oursler, S T Brown, R S Braithwaite, M May, K E Covinsky, M S Roberts, S L Fultz, K J Bryant; VACS Project Team
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Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers

Amy C Justice et al. HIV Med. 2010 Feb.

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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Figures

Fig. 1
Fig. 1
Observed mortality rate by quintiles of risk estimated using HIV only and combined HIV and ‘non-HIV’ biomarkers.
Fig. 2
Fig. 2
Discrimination of Veterans Aging Cohort Study (VACS) Index (C statistic) by survival interval (n =9748).
See this image and copyright information in PMC

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