Understanding and Controlling Chronic Immune Activation in the HIV-Infected Patients Suppressed on Combination Antiretroviral Therapy

Combination antiretroviral therapy (cART) has resulted in tremendous gains in survival among HIV-infected patients, but as a group those who achieve undetectable viral loads on cARTexperience a greater degree of immune activation and inflammation than the general population. HIV-infected patients continue to experience premature immune senescence with earlier and more frequent non-AIDS events compared to HIV-uninfected individuals. Chronic immune activation during suppressive cART derives from a variety of sourcesmediated by cytokines, chemokines, coagulation, microbial translocation, immune regulators and Teffector cell activation abnormalities, among others. Current investigational strategies to control immune activation target potential causes of persistently heightened immune activation during cART such as microbial translocation, co-infections, and comorbidities or mediators along a common final pathway. Although several interventions have shown promise in vitro or in preliminary clinical trials, no intervention has sufficient evidence for routine use, making control of immune activation during cART an unmet need.