Residual inflammation and viral reservoirs: alliance against an HIV cure

Abstract

Purpose of review: HIV persists in cellular and anatomical reservoirs during antiretroviral therapy (ART). Viral persistence is ensured by a variety of mechanisms including ongoing viral replication and proliferation of latently infected cells. In this review, we summarize recent findings establishing a link between the unresolved levels of inflammation observed in virally suppressed individuals on ART and the mechanisms responsible for HIV persistence.

Recent findings: Residual levels of viral replication during ART are associated with persistent low levels of immune activation, suggesting that unresolved inflammation can promote the replenishment of the HIV reservoir in tissues. In addition, the recent findings that the latent HIV reservoir is maintained by continuous proliferation of latently infected cells provide another mechanism by which residual inflammation could contribute to HIV persistence.

Summary: Residual inflammation during ART is likely to be a critical parameter contributing to HIV persistence. Therefore, reducing inflammation may be an efficient way to interfere with the maintenance of the HIV reservoir in virally suppressed individuals on ART.

Figure 1

In HIV-infected, ART-suppressed subjects, the latent reservoir (red wheel) is maintained by continuous proliferation of latently infected cells, which can produce viral particles upon activation constituting the productive reservoir (turquoise wheel). When reactivated cells are in anatomical/cellular sanctuaries, where ART cannot diffuse efficiently, residuals levels of viral replication can occur (blue wheel), fueling continuously the latent reservoir. Increased levels of immune activation and/or inflammation promote the three mechanisms of HIV persistence (small wheels). Several therapeutic strategies designed to act directly on viral production/replication or to modulate the immune cells could be used to interrupt this vicious circle.