Elevated plasma levels of lipopolysaccharide and high mobility group box-1 protein are associated with high viral load in HIV-1 infection: reduction by 2-year antiretroviral therapy

Objective: To investigate plasma levels of high mobility group box-1 protein (HMGB1), a marker of tissue necrosis and immune activation, as well as lipopolysaccharide (LPS), a marker of bacterial translocation, in HIV-1-infected patients. Design: We studied 32 HIV-1-positive patients who had responded to antiretroviral therapy with undetectable viremia after 2 years, 10 nonresponders and 19 healthy controls. Methods: HMGB1 was analyzed by ELISA, and LPS by Lamilus colometric assay. Nonparametric statistics were applied. Results: In naive HIV-1 patients, HMGB1 and LPS were elevated as compared with controls (P<0.001). LPS levels were higher in African and Oriental patients compared with whites (P=0.007). Notably, viral load was two-fold higher in patients with LPS, and HMGB1 was above median as compared with other patients (P=0.005). This association was largely driven by African patients, who had a five-fold increased viral load in the presence of elevated LPS and HMGB1. After 2 years of effective antiretroviral therapy, LPS was reduced to the same median level as in the control group (P<0.001), and HMGB1 was also reduced (P=0.001), whereas no reductions were seen in nonresponders. Conclusion: The new findings are the association of elevated plasma levels of LPS and HMGB1 with high viral load, as well as the normalized levels of LPS, and the reduction of HMGB1 after 2 years of effective antiretroviral therapy. As LPS and HMGB1 tend to form immunologically active complexes in vitro, we propose that such complexes may be involved in the immune activation and pathogenesis of HIV-1 infection. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins