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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.