Jennifer Zerbato

This session, chaired by Dr. Maud Mavigner from Emory University, highlighted the importance of different CD4+ T cell subsets to the complexity of the latent reservoir, both in children and adults. It also discussed how host genetic factors may influence the size of the latent reservoir in PWH on ART.

Daniel Reeves introduced the passenger hypothesis, describing the fine balance between cellular proliferation and cell death across T cell subsets that maintain the latent reservoir over time. Due to proliferation of HIV-infected cells is the dominant mechanism of reservoir persistence, strategies aimed at reducing the HIV reservoir need to consider both proliferation and differentiation mechanisms. Wim Trypsteen identified SNPs that correlated with HIV reservoir size, finding genetic associations of PTDSS2, RNH1, and IRF7 with HIV DNA and RNA/DNA ratios, as the SNP in IRF7 was associated with higher expression levels of IRF7 gene. Moreover, increased IFN gamma levels were produced from ex vivo PBMCs when stimulated with a TLR agonist. These data highlight novel molecular mechanisms involved in HIV reservoir establishment and maintenance that need to be further explored. Stay tuned! Finally, Jade Canape demonstrated that naïve (TN) CD4+ T cells in vertically-infected children and adolescents were the main contributing cell type to the translation-competent reservoir in all age groups under 18yo, with a distribution profile progressively transitioning to that of adults over time. These data highlight the importance of TN cells in reservoir and cure studies, particularly in young individuals, which are often overlooked or excluded.

Despite many years of intense characterization of the latent HIV reservoir, there is still a great deal that we do not understand in HIV persistence and maintenance and how we may target specific factors in HIV cure strategies. This session expertly highlighted that multiple mechanisms that maintain the HIV reservoir need to be targeted to reduce levels of HIV DNA and how host genetic factors may influence the size and composition the latent reservoir. Lastly, it was shown that the reservoir is different in children versus adults and that TN cells are a major player in HIV persistence.