Inflammatory Mechanisms in HIV-Associated Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a severe complication of human immunodeficiency virus (HIV) infection and a leading major cause of death when present. HIV-PAH could be the consequence of multiple hits including the direct effects of HIV proteins, use of illicit drugs, and chronic inflammation. Indeed, HIV infection has long been identified as an immunosuppressive disease but, since the advent of highly active antiretroviral treatments (HAART), HIV infection is considered as an inflammatory disease in which vascular complications have become a major cause of morbidity and death. Conversely to immunosuppression, which correlates with blood CD4 + T cell level, inflammation in HIV infection is due to the lack of gut CD4 + T cell restoration. Such gut T cell depletion favors lipopolysaccharide translocation and, in turn, chronic systemic interleukin-6 overproduction. Conversely to blood CD4 + T cells, gut CD4 + T cells are only partially restored with HAART, usually slowly after several months or years, with a large heterogeneity from one patient to another. These characteristics may cause chronic inflammation, and we hypothesize that PAH may occur because of this inflammatory component despite HAART, even with apparently good response to therapy (i.e., blood CD4 + T cell normalization and undetectable HIV load). Inflammation theory in HIV-PAH (as in other forms of PAH) could open new treatment options.

Keywords

human immunodeficiency virus - inflammation - interleukin-6 - lipopolysaccharide - pulmonary arterial hypertension

• References

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