Can early therapy reduce inflammation?

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.

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.

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.