Recent studies suggest higher cumulative HIV viremia exposure measured as viremia copy-years (VCY) is associated with increased all-cause mortality. The objectives of this study are (1) report the association between VCY and all-cause mortality and (2) assess associations between common patient characteristics and VCY. METHODS: Analyses were based on patients recruited to the Australian HIV Observational Database (AHOD) who had received =24 weeks of antiretroviral therapy (ART). We established VCY after 1, 3, 5, and 10 years of ART by calculating the area under the plasma viral load time series. We used survival methods to determine the association between high VCY and all-cause mortality. We used multivariable mixed-effect models to determine predictors of VCY. We compared a baseline information model with a time-updated model to evaluate discrimination of patients with high VCY. RESULTS: Of the 3021 AHOD participants who initiated ART, 2073 (69 ), 1667 (55 ), 1267 (42 ), and 638 (21 ) were eligible for analysis at 1, 3, 5, and 10 years of ART, respectively. Multivariable-adjusted hazard ratio association between all-cause mortality and high VCY was statistically significant, hazard ratio 1.52 (1.09, 2.13), P = 0.01. Predicting high VCY after 1 year of ART for a time-updated model compared with a baseline information model, the area under the sensitivity/specificity curve was 0.92 vs. 0.84; and at 10 years of ART, area under the sensitivity/specificity curve was 0.87 vs. 0.61, respectively. CONCLUSION: A high cumulative measure of viral load after initiating ART is associated with increased risk of all-cause mortality. Identifying patients with high VCY is improved by incorporating time-updated information. ? 2013 by Lippincott Williams and Wilkins.