Targeting HIV-infected macrophages to facilitate HIV cure

Anti-HIV therapy suppresses HIV replication and prevents AIDS, however HIV currently cannot be cured and continuous, life-long therapy is required. HIV cure is possible, but extremely challenging, and a much better understanding of what governs the maintenance and elimination of HIV-infected cells is required to achieve this goal. The greatest barrier to HIV cure is the persistence of HIV in a latent state in infected cells and these reservoirs of HIV reactivate if therapy is stopped. Whilst CD4+ T cells contain most of this latent HIV reservoir in blood, HIV also infects myeloid cells including macrophages in tissues and these reservoirs are an important, clinically relevant source of resurgent HIV replication when therapy is stopped. Despite their importance, HIV cure strategies rarely consider HIV-infected macrophages and there is a dearth of knowledge regarding this reservoir and how it can be eliminated. Objective: The overall objective of this work is to identify strategies to eliminate reservoirs of HIV within macrophages and facilitate their elimination by the immune system to help achieve a HIV cure. This project will use a novel, primary cell model of latent HIV-infection in macrophages we have developed in our lab together with unique clinical samples from people with HIV to: • Identify agents which are able to reactivate HIV in latently-infected macrophages. • Analyse latent HIV infection in different macrophage subtypes (gut, lung etc). • Use novel single cell RNASeq technology to characterise cellular processes driving latent HIV infection in macrophages. • Explore the use of novel therapeutics to facilitate the death of HIV-infected macrophages. Techniques involved: Cell culture, immunophenotyping/flow cytometry, in vitro HIV infection (under PC3 conditions), fluorescence microscopy, single cell RNA Sequencing.