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Biomarkers Linked to More Deaths After HIV Treatment

IL-6, D-dimer associated with higher risk of death in patients receiving intermittent treatment

THURSDAY, Oct. 23 (HealthDay News) -- Increased serum levels of two biomarkers are associated with an increased risk of death in HIV-infected patients receiving intermittent antiretroviral treatment, according to an article published online Oct. 21 in PLoS Medicine.

Lewis H. Kuller, M.D., from the University of Pittsburgh, and colleagues measured the levels of six biomarkers in HIV-infected patients who had been enrolled in a clinical trial where they were randomized to either intermittent antiretroviral treatment based on CD4 levels or continuous treatment. The trial had showed higher mortality in the intermittently treated group. Biomarker levels were measured for 85 deaths and 170 matched controls, and for 249 intermittently treated patients and 250 continuously treated patients.

The researchers found a significant association between mortality and higher levels of high sensitivity C-reactive protein (unadjusted odds ratio, highest versus lowest quartile, 2.0), interleukin (IL)-6 (OR, 8.3) and D-dimer (OR, 12.4) at study entry. They also found that one month after randomization, IL-6 levels increased significantly in the intermittently treated group compared with the continuously treated group (30 versus 0 percent), while D-dimer levels also significantly increased in the intermittently treated group compared with the continuously treated group (16 versus 5 percent). Increases in both markers after one month were associated with HIV-RNA levels in the intermittently treated group, the authors note.

"IL-6 and D-dimer were strongly related to all-cause mortality," Kuller and colleagues conclude. "Taken together, these findings suggest that HIV-induced activation of inflammatory and coagulation pathways has an adverse effect on all-cause mortality among patients with relatively preserved CD4+ counts, and that interrupting antiretroviral treatment may further increase this risk by raising IL-6 and D-dimer levels."

Three of the study authors disclosed financial ties to pharmaceutical companies.

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