Abstract

This article describes the use of biomarkers in expanding our understanding of chronic non-AIDS comorbidities among persons living with HIV (PLWH) receiving antiretroviral therapy (ART). We review current evidence that biomarkers of chronic immune activation and inflammation associate with a broad spectrum of end-organ diseases in PLWH. We discuss how ART may impact inflammation associated with HIV infection and the degree to which inflammation persists despite effective suppression of viral replication in plasma. We then discuss the limitations of the current literature, which lacks evidence of causality and disproportionately involves a few protein biomarkers that are unable to disentangle complex and overlapping biological pathways. Premature end-organ disease among PLWH has been repeatedly associated with higher levels of blood biomarkers reflecting inflammation and immune activation, which, despite viral suppression and CD4 T-cell increases after ART treatment, remain elevated relative to uninfected persons. There remain important unanswered questions with implications for the development of anti-inflammatory treatment strategies aimed at mitigating excess risk for end-organ comorbidities among PLWH.

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