This is the first essential step towards an integrated surrogate endpoint for research and a potentially useful risk index for clinical management. Rapamycin cell line Our study has unique advantages over previously published work. We had sufficient sample size and longitudinal follow-up to analyse all cause mortality among a sample of patients with uniform data sources and methods of data collection and near complete mortality ascertainment [29,30]. We were able to study an older population, ensuring the relevance of this work to the rapidly growing population of older patients with HIV infection [39]. Importantly, we were able to demonstrate

that our results generalized to an independent sample before and after accounting for missing data. Our study also has limitations. The first course of cART within the VA may not be the first course of cART. We conducted an eight-site chart review (n=3250) demonstrating that 75% of veterans are cART naïve at VA entry, but some individuals probably had prior cART exposure. Additionally, there were few women in the sample and we cannot determine whether our findings generalize beyond men. Future work is planned that will explore whether additional clinical data,

laboratory data, and time-updated analyses improve ZD1839 supplier the index. Data on smoking, wasting, cancer diagnoses, cardiovascular and cerebral vascular disease, pulmonary disease, microalbumin, anaemia type and short-term response to cART may all further improve the differentiation of mortality risk. Additionally, when more standardized and clinically available, markers of inflammation and immune senescence may prove valuable. It will also be useful to test the discrimination of the index for other important patient outcomes including specific causes of death, functional compromise and hospitalization. before Nevertheless, the

VACS Index currently predicts mortality as well as two established prognostic indices when evaluated over comparable survival intervals (a major determinant of prognostic accuracy) [31,39]. For 30-day survival, the index achieved C statistics of 0.86 (95% CI 0.80–0.91), consistent with the range of performance of the APACHE III, a prognostic index for short-term hospital or 30-day intensive care unit survival (C statistics between 0.70 and 0.86) [40–42]. For 1-year survival, the VACS index achieved a C statistic of 0.81 (95% CI 0.80–0.83), which compares favourably to that for the Charlson Index (C statistic 0.70–0.77) [43]. It is important to note that the index discriminated reasonably well over all survival intervals analysed, which suggests that it offers a reasonable risk assessment of both short- and long-term mortality [31]. Of note, some question whether findings among veterans apply to nonveteran populations.