MOPE113 - Poster Exhibition
Immune reconstitution on HAART defines survival in US veterans
H. Drechsler1,2, S. Zhang1,2, M. Holodniy3, R. Bedimo1,2
1Dallas VA Medical Center, Medicine, Dallas, United States, 2University of Texas Southwestern, Medicine, Dallas, United States, 3VA Palo Alto Health Care System, Medicine, Palo Alto, United States
Background: The CD4+ T-cell threshold associated with increased all cause mortality in virologically suppressed patients on HAART has been debated and the relative impact of HAART adherence and intermittent viremia in this setting is unknown.
Methods: Using the US Veterans Administration (VA) Clinical Case Registry data we determined clinical follow-up time and death rates after first prescription of HAART within the VA system. We calculated annual AUC averages for CD4 and CD8 values and the fraction and annual AUC averages for lymphocytes that were CD4 and CD8 negative (composed almost equally of B-cells and CD3-CD19- lymphocytes). We determined annual refill rates for individual antiretrovirals and overall HAART adherence, and categorized annual rates for viremia after starting HAART. This information was then used to build a Cox model with time dependent variables calculating the hazard of death while controlling for demographic, immunologic, and virologic baseline covariates.
Results: In multivariate analysis of 13,570 virologically suppressed veterans on HAART with a minimal follow up of 1.5 years (median 7.3 years) 944 deaths were counted. CD4 recovery to less than 700 cells/µL, HCV co-infection, older age, and low nonCD4CD8 lymphocyte counts were predictors with the highest significance level (p< 0.0001). Measured HAART adherence as a continuous variable had a strong protective effect while the impact of sporadic low-level viremia < 1000 copies/mL on mortality was not statistically significant. Low CD8 values and recent stavudine use were also associated with increased mortality.
Conclusions: Average CD4 counts < 700 cells/µL and low CD8 and nonCD4CD8 lymphocyte counts were independently associated with increased mortality in patients on suppressive HAART. 'Normalization' of CD4 counts to levels >500 cells/µL on HAART may not be sufficient to minimize the risk of death.
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