Author: Mark Mascolini
28 July 2010
CD4 slope—the rate at which CD4 counts fall over a given period—was the best predictor of all-cause mortality and non-AIDS deaths in people taking standard triple therapy (and not interleukin 2 [IL-2]) in two large international studies of IL-2. Latest CD4 count was the best predictor of liver and kidney disease in this analysis, but not of cardiovascular disease or non-AIDS cancers.
ESPRIT and SILCAAT investigators analyzed CD4 changes in 3012 people who received standard antiretroviral therapy during the trials but did not take IL-2. The CD4 measures analyzed were latest, initial, and nadir CD4 count; latest CD4 percent; time spent with CD4 count below certain thresholds; and CD4 slopes.
Non-AIDS deaths were over 6 times more frequent than AIDS deaths in the study population, at a rate ratio of 6.48 (95% confidence interval [CI] 1.65 to 1.79). And non-AIDs events (new diagnoses) were almost twice as common as AIDS events (rate ratio 1.72, 95% CI 1.65 to 1.79).
Latest CD4 count strongly predicted a lower overall risk of death: every log2 higher latest CD4 count halved the overall death risk (hazard ratio [HR] 0.48, 95% CI 0.43 to 0.54).
After statistical adjustment for latest CD4 count, CD4 slope over seven visits was the only variable assessed that independently predicted all-cause mortality and non-AIDS deaths. A CD4 loss of less than -10 cells/μL per month versus 0 +/- 10 cells/μL tripled the all-cause death risk (hazard ratio [HR] 3.04, 95% CI 1.98 to 4.67) and more than doubled the non-AIDS death risk (HR 2.62, 95% CI 1.62 to 4.22).
Every log2 higher latest CD4 count halved the risk of new liver complications (HR 0.46, 95% CI 0.33 to 0.63) and cut the risk of new kidney diagnoses more than 60% (HR 0.39, 95% CI 0.21 to 0.70). But latest CD4 count did not predict cardiovascular complications or non-AIDS cancers.
“Latest CD4+ cell count is the best predictor of serious endpoints,” the investigators conclude. “CD4+ slope independently predicts all-cause and non-AIDS deaths.”
Source: Amit C. Achhra, Janaki Amin, Matthew G. Law, Sean Emery, Jan Gerstoft, Fred M. Gordin, Michael J. Vjecha, James D. Neaton, David A. Cooper, for INSIGHT ESPRIT and SILCAAT study groups. Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients. AIDS.
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