24 Jul 2019
IAS 2019: Thomas Rasmussen’s Mexico Musings
We asked the Doherty Institute's contingent who headed to the 10th International Aids Society Conference on HIV Science in Mexico, to share their insights as the week unfolds.
Here, Associate Clinical Director of HIV Cure Studies Dr Thomas Rasmussen shares her reflections on two of the inspiring talks he has heard so far.
Monday 22 July 2019, Dr Nadia Roan, UCSF: Use of high-dimensional single-cell analysis to characterise cells latently infected with HIV
One key challenge in HIV cure research is to identify cells that are latently infected with HIV, ie cells that contain but do not express HIV.
Dr Nadia Roan from the University of California San Francisco presented data to illustrate how a new technological method called CyTOF (cytometry by time of flight) and multi-dimensional analyses can be applied to identify the phenotype of latently infected CD4+ T memory cells. This was done by first analysing the expression of >40 markers on cells from people living with HIV on antiretroviral therapy.
Using multi-dimensional analyses these data were used to generate a map of how the cells cluster according to these markers. They then activated the cells to identify which cells contain functional virus and illustrated how these cells could then be placed onto the previously generated map. This way they are potentially able to predict whether cells that go on to produce functional virus may have particular characteristics. Pending further development, this approach might be useful to identify cells that are latently infected with HIV.
Tuesday 23 July 2019, Dr David Margolis, Latency reversal
In an overview talk on strategies to activate the latent HIV reservoir, Dr David Margolis from University of North Carolina, showed data on the pre-clinical characterisation on a AZD5582. This is a SMAC mimetic, a class of compounds that can induce apoptotic pathways. He presented data showing that AZD5582 can activate latent HIV in both cell lines, primary CD4+ T cells, HIV-infected humanised mice and SIV-infected non-human primates. Moreover, in comparison with other latency-reversing agents, AZD5582 had minimal effects on human gene expression.
These data suggest that AZD5582, pending further characterisation of its clinical profile, could be a promising candidate to activate latent HIV with the aim of exposing infected cells to killing by the immune system.