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

BACKGROUND: 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. METHODS: 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. RESULTS: 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]. CONCLUSION: High IL-6 levels and inflammatory burden score were associated with mortality in a cohort of HIV-infected adults with alcohol problems.