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The effect of HIV infection on the host response to bacterial sepsis. Bacterial sepsis is an important cause of morbidity and mortality in patients with HIV. HIV causes increased susceptibility to invasive infections and affects sepsis pathogenesis caused by pre-existing activation and exhaustion of the immune system. We review the effect of HIV on different components of immune responses implicated in bacterial sepsis, and possible mechanisms underlying the increased risk of invasive bacterial infections. We focus on pattern recognition receptors and innate cellular responses, cytokines, lymphocytes, coagulation, and the complement system. A combination of factors causes increased susceptibility to infection and can contribute to a disturbed immune response during a septic event in patients with HIV. HIV-induced perturbations of the immune system depend on stage of infection and are only in part restored by combination antiretroviral therapy. Immunomodulatory treatments currently under development for sepsis might be particularly beneficial to patients with HIV co-infection because many pathogenic mechanisms in HIV and sepsis overlap.