Chronic Inflammation in HIV Pathogenesis: Effects on Immune Cells, Organ Systems, and Systemic Consequences

Abstract Chronic inflammation in HIV infection arises mainly from a gut breach that occurs early in infection. The breach is followed by microbial translocation which activates a myriad of immune components and is not fully rescued by antiretroviral therapy (ART). T cells are activated, memory B cells and natural killer cells have abnormal function, neutrophils become suppressive, and platelets are activated. Monocyte and macrophages become pro-inflammatory and their activation is associated with systemic inflammation which subsides in treated HIV infection but does not return to normal. Recovery of CD4 T cells after ART treatment is linked to levels of chronic inflammation. Multiorgan systems are affected by chronic inflammation during HIV infection including liver and kidney. Other comorbidities are increased including cardiovascular disease, lipodystrophy, and reduced neurocognition which are all associated with increased levels of inflammation. Accelerated aging post-ART may also occur. In many ways, this confluence of effects can resemble obesity, which is also characterized by microbial translocation and chronic inflammation.