Inflammatory cytokines and mortality in a cohort of HIV-infected adults with alcohol problems

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HIV infection leads to chronic inflammation and alterations in levels of inflammatory cytokines. The association between cytokine levels and mortality in HIV infection is not fully understood. We analyzed data from a cohort of HIV-infected adults with alcohol problems who were recruited in 2001-2003, and were prospectively followed until 2010 for mortality using the National Death Index. The main independent variables were inflammatory biomarkers [interleukin-6 (IL-6), IL-10, tumor necrosis factor-α, C-reactive protein, serum amyloid A, monocyte chemotactic protein-1, and cystatin-C], measured at baseline in peripheral blood and categorized as high (defined as being in the highest quartile) vs. low. A secondary analysis was conducted using inflammatory burden score, defined as the number of biomarkers in the highest quartile (0, 1, 2 or ≥ 3). Cox models were used to assess the association between both biomarker levels and inflammatory burden with mortality adjusting for potential confounders. Four hundred HIV-infected patients were included (74.8% men, mean age 42 years, 50% hepatitis C virus-infected). As of 31 December 2009, 85 patients had died. In individual multivariable analyses for each biomarker, high levels of IL-6 and C-reactive protein were significantly associated with mortality [hazard ratio=2.49 (1.69-5.12), P<0.01] and [hazard ratio=1.87 (1.11-3.15), P=0.02], respectively. There was also a significant association between inflammatory burden score and mortality [hazard ratio=2.18 (1.29-3.66) for ≥ 3 vs. 0, P=0.04]. In the fully adjusted multivariable analysis, high levels of IL-6 remained independently associated with mortality [hazard ratio=2.57 (1.58-4.82), P<0.01]. High IL-6 levels and inflammatory burden score were associated with mortality in a cohort of HIV-infected adults with alcohol problems.