Immune activation and HIV persistence: considerations for novel therapeutic interventions

Abstract

Purpose of review: One of the potential barriers to current HIV cure strategies is the persistence of elevated levels of immune activation despite otherwise effective antiretroviral therapy (ART). The purpose of this review is to examine the relationship between immune activation and HIV persistence, and to review the novel therapeutic interventions that are currently being pursued to target immune activation in treated HIV disease.

Recent findings: Multiple groups have consistently observed that elevated levels of inflammation, immune activation, and immune dysfunction persist in ART-treated individuals, despite the successful suppression of plasma viremia. Increased immune activation may lead to viral persistence through multiple mechanisms. Several novel interventions aimed at decreasing persistent immune activation are being pursued and include studies aimed at decreasing low-level viral replication, approaches aimed at decreasing microbial translocation, interventions to treat co-infections, and therapies that directly target immune activation.

Summary: There appears to be a clear and consistent relationship between immune activation and viral persistence in treated HIV disease. Whether this relationship is causal or mediated through other mechanisms is still unknown. Small-scale, pathogenesis-oriented interventional studies are necessary to further evaluate this relationship and the effect of potential interventions.