Inflammation and Fibrosis in HIV: Getting to the Heart of the Matter.

Abstract

The treatment and disease course of HIV infection have changed dramatically since the discovery of HIV in 1983. AIDS, once the axiomatic cause of early death in HIV-infected individuals, has now become an uncommon complication among individuals treated with antiretroviral therapy (ART). However, with the success of ART comes new challenges for the HIV-infected, namely a substantial burden of cardiovascular disease (CVD). HIV infection is associated with high rates of CVD complications, including acute myocardial infarction,1 sudden cardiac death,2 and heart failure.3 See Articles by Luetkens et al and Ntusi et al The mechanisms leading to CVD in HIV remain incompletely understood. HIV-infected individuals often have a greater burden of traditional cardiac risk factors, though such traditional risk factors alone do not nearly account for the observed increased risk. A wealth of research suggests that, paradoxically, chronic upregulation of inflammatory activity, which is present even among antiretrovirally treated and suppressed individuals, may play an important role in predicting mortality, CVD as well as other non-AIDS conditions.4–6 Although the hallmark of untreated HIV infection is an immunodeficient state, treated, virally suppressed HIV disease is associated with immune activation.7–9 Numerous potential causes are thought to contribute to this immune activation, including toxicity from ART, low-level viral replication, and disease-mediated shifts in inflammatory cell subsets, among other mechanisms. Delineation of the precise mechanisms underlying immune activation in HIV, as the driver of cardiovascular complications, is the focus of an increasing number of studies. In line with the inflammatory hypothesis of CVD complications in HIV, several studies have clearly established the predictive value of inflammatory and coagulation biomarkers for CV events and mortality in HIV. …