Novel Insights into a Functional HIV Cure

Although efficient suppression of HIV replication below the detection limits is possible using antiretroviral therapy (ART), the risk of adverse effects and drug resistance, as well as the physical and economic burdens of lifelong treatment still exist. Moreover, viremia rebounds within a few weeks upon ART cessation, even after prolonged comprehensive treatment. This has been ascribed to productive and latently infected cells, which establish a reservoir that persists during ART, and is a source of re-infection upon therapy interruption. The reservoir is seeded early during the acute stages of HIV infection, with lymphoid tissues carrying the highest burden. This pool of infected cells is homeostatically maintained, clonally expanded, and overall represents the final unmet challenge towards an HIV cure. Some individuals, termed ‘elite controllers’, exhibit natural immunity that enables them to control HIV without treatment. Similarly, some SIV-positive non-human primates, such as old world monkeys, do not naturally exhibit severe symptoms, despite efficient viral replication. Both cases represent examples of natural virus control, through mechanisms yet undiscovered.

A functional HIV cure has not been achieved with current antiretroviral therapies, due to a persistent reservoir formed within lymphocytes and monocytes, such as long-lived memory CD4 T-cells and macrophages. However, the cell subsets composing the persistent reservoir pools have not entirely been characterized. In addition, the anatomical compartments in which the viral reservoir is primarily maintained, as well as the cellular machinery hijacked for HIV persistence remain yet unrevealed. Therefore, it is crucial to establish greater insight into the chronic stages of HIV infection and pathogenesis, to aid in the design strategies for a functional cure. Alternatively, it is possible to live with HIV without severe symptoms, as is the case for elite controllers. A better understanding of the genetics and immune responses developed in elite controllers will offer new frontiers for a cure. Furthermore, the detailed interactions between other mammals and their immunodeficiency viruses could provide novel HIV treatment strategies.

This Research Topic will welcome articles focusing on the following themes:

• Mechanisms of HIV reservoir establishment during early infection
• Novel detection methods of HIV reservoirs based upon DNA, RNA and Proteins
• Characterization of tissue-localized actively and latently infected cells
• Host-virus interactions and virulence at acute and chronic infection
• Novel immunotherapy-based functional cure strategies

Topic Editor Luca Sardo is employed by company Merk & Co. All other Topic Editors declare no competing interests with regard to the Research Topic subject.