Using chart review, we have determined that 75% of those entering care in the VA for HIV infection initiate their first course of cART after coming to the VA. To ensure adequate Cobimetinib ic50 follow-up time, we identified subjects who initiated their first course of cART in the VA between 1 January 1997 and 1 August 2002. We used pharmacy data to identify individuals initiating a minimum of three antiretroviral medications and laboratory data to determine that

they had received a minimal evaluation (CD4 cell count, HIV-RNA and haemoglobin) within 6 months of initiating cART. Available data included demographic factors (age, race/ethnicity and gender), administrative diagnostic codes [International Statistical Classification of Diseases and Related Health Problems (ICD)-9 codes], routinely collected clinical laboratory data, pharmacy data and long-term mortality. All laboratory data were collected from the clinical sites through the Immunology Case Registry [26]. Pharmacy data are drawn from the national VA Pharmacy Benefits Management Package [27]. ICD-9 codes

were used to determine diagnoses of drug abuse or dependence, alcohol abuse or dependence, and AIDS-defining illnesses. Hepatitis C was defined as a positive antibody, qualitative or quantitative HIV RNA, or ICD-9 codes. Hepatitis B was defined as a positive selleck chemical surface antigen test or ICD-9 codes. In all cases in which ICD-9 codes were used, two out-patient or one in-patient code was required before the condition was considered present. This approach improves the accuracy of ICD-9 codes when compared with chart review [28]. The specific codes used can be found at our website (http://VAcohort.org). All cause mortality data using VA data sources have been demonstrated to be accurate and complete when compared with the National Death Registry [29,30]. We ran univariable descriptive statistics and estimated the association between biomarkers using Spearman rank for continuous variables

and χ2 for dichotomous markers. We then split the sample. Those Farnesyltransferase who initiated treatment after 31 December 1998 were assigned to the development set and those who initiated treatment on or before this date were reserved for validation. We initially standardized the maximal observation interval for both samples to 6 years, but later conducted sensitivity analyses around this maximal survival window. We chose a nonrandom split based on calendar time to determine the temporal generalizability of our findings [32]. After each model had been fully specified we used the assigned risk estimates from the model to rank patients according to risk from highest to lowest risk of mortality. We compared Poisson, Weibull and Cox survival models and found that differences in distributional assumptions over the 6-year window did not substantially alter coefficient weights. We present Poisson analyses, as these results are the most directly interpretable.