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

Abstract

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). 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. 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. 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.