Netanya G Sandler1, Irini Sereti. 1. aInfectious Diseases Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas bLaboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Abstract
PURPOSE OF REVIEW: Serious non-AIDS events or noninfectious complications of HIV infection far outnumber AIDS events in the current combination antiretroviral therapy (ART) era and are attributed to chronic inflammation. Thus, a better understanding of why inflammation persists on ART will assist in developing better therapeutic strategies, including optimal timing of ART initiation. RECENT FINDINGS: Markers of inflammation and coagulation, such as D-dimer, interleukin-6, C-reactive protein, soluble CD14, and soluble CD163, predict end-organ disease and mortality, whereas markers of T-cell activation appear more predictive of CD4 T-cell decline, AIDS events, or response to therapy. Initiating ART at high CD4 T-cell counts can result in less inflammation as supported by studies in acute and early HIV infection, but antiretroviral drugs may differentially affect inflammatory pathways. Decreasing inflammation in HIV-uninfected individuals may decrease morbidity, but long-term outcomes studies in HIV-infected individuals are lacking. SUMMARY: Circulating biomarkers of inflammation are among the strongest predictors of non-AIDS outcomes in treated HIV infection. With additional investigation, they may serve in the future as specific end-organ disease surrogate endpoints and may help identify those patients at highest risk of non-AIDS events who may benefit from either early ART and/or potential adjuvant anti-inflammatory therapies.
PURPOSE OF REVIEW: Serious non-AIDS events or noninfectious complications of HIV infection far outnumber AIDS events in the current combination antiretroviral therapy (ART) era and are attributed to chronic inflammation. Thus, a better understanding of why inflammation persists on ART will assist in developing better therapeutic strategies, including optimal timing of ART initiation. RECENT FINDINGS: Markers of inflammation and coagulation, such as D-dimer, interleukin-6, C-reactive protein, soluble CD14, and soluble CD163, predict end-organ disease and mortality, whereas markers of T-cell activation appear more predictive of CD4 T-cell decline, AIDS events, or response to therapy. Initiating ART at high CD4 T-cell counts can result in less inflammation as supported by studies in acute and early HIV infection, but antiretroviral drugs may differentially affect inflammatory pathways. Decreasing inflammation in HIV-uninfected individuals may decrease morbidity, but long-term outcomes studies in HIV-infected individuals are lacking. SUMMARY: Circulating biomarkers of inflammation are among the strongest predictors of non-AIDS outcomes in treated HIV infection. With additional investigation, they may serve in the future as specific end-organ disease surrogate endpoints and may help identify those patients at highest risk of non-AIDS events who may benefit from either early ART and/or potential adjuvant anti-inflammatory therapies.
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