06 Nov 2020
ACH2 summary from Dr Thomas Rasmussen
Dr Thomas Rasmussen, Associate Clinical Director of HIV Cure Studies at Doherty Institute attended the ACH2 2020 Conference this week. Here he reflects on presentations from Doherty Institute researchers looking at understanding the mechanisms that allow HIV to persist long-term in people with HIV despite suppressive antiretroviral therapy (ART).
The session opened with a fascinating keynote address from Doherty Institute Director, Professor Sharon Lewin where she provided an overview of the role of immune checkpoints for HIV persistence on ART and the potential role of immune checkpoint blockers in therapeutic strategies for an HIV cure. Immune checkpoints blockers are therapeutic antibodies that are being developed for use as cancer immunotherapy but owing to their ability to activate T cells, these antibodies may also have a role for activating latent HIV and/or boosting the immune response against HIV-infected cells. Professor Lewin presented data that illustrated how various combinations of immune checkpoint antibodies with specific targets may be effective in enhancing anti-HIV immunity.
The role of immune checkpoints for HIV persistence and the virological and immunological effects of blocking immune checkpoints remained a dominant theme of the session. Doherty Institute collaborator, The Alfred’s Dr Jillian Lau presented a study of three people with HIV that received immune checkpoint antibodies as cancer treatment. Although limited by the low number of participants, this study indicated that blocking immune checkpoints can activate expression of latent HIV such that infected cells become visible to the immune system. The study also provided an example that these antibodies can boost HIV-specific immune responses.
In a similar study using samples from people with HIV receiving immune checkpoint antibodies for cancer, one of my colleagues from the Lewin Lab, Dr Celine Gubser showed data from a study still in progress, where she identified individuals who displayed an anti-HIV response to immune checkpoint blockade defined as an increase in cytotoxic T cells responding to HIV antigens. The study will now use gene expression analyses to search for characteristics that may help identify which cellular mechanisms are underlying an effective anti-HIV response to immune checkpoint blockade. I presented data from a clinical study that was designed to investigate the role of specific immune checkpoints, called PD1 and CTLA4, for HIV persistence. We found that cells that express both these markers harbour HIV more frequently compared to cells that do not express PD1 and CTLA4.