Ellen Bowden-Reid
HIV Cure Snapshot
The Australasian HIV&AIDS Conference (commonly known as ASHM after the organiser, the Australasian Society for HIV Medicine) was held online from 16-20 November 2020. Here are some highlights of cure-related presentations.
Understanding HIV latency
The HIV Cure presentations commenced with Professor Sharon Lewin (Doherty Institute for Infection and Immunity). Professor Lewin introduced some of the exciting new concepts that are helping to unravel the spectrum of HIV latency. These include reservoir activity, clonal expansion, characterisation of integration sites and distinguishing between defective and intact provirus. This was followed by an overview of clinical strategies for achieving a HIV cure, including some recent and ongoing combined immunotherapy clinical trials (RIVER, ROADMAP, TITAN, UCSF).
Professor Sarah Palmer (Westmead Institute for Medical Research) shared insights into the intricate genetic landscape of latent HIV. Her group found that effector memory T cells (TEM) had higher proportions of full length provirus than other T cell subsets. The proportion of full length provirus increased over time. Strikingly, while TEM with provirus with intact gag and nef increased over time, provirus with intact gag and defective nef decreased. This suggests a potential role of nef in HIV persistence.
Immune checkpoints
Dr. Thomas Rasmussen (Doherty Institute for Infection and Immunity) delivered a detailed look into the expression of immune checkpoints in HIV positive adults. He showed that memory CD4+ T cells that were positive for both the immune checkpoints CTLA-4 and PD-1 were enriched with total HIV DNA (PRADA Study), making these cells a good target for anti-checkpoint antibodies. Further, the AMC-095 phase 1 clinical trial found that anti-CTLA-4 and anti-PD-1 acted as latency reversing agents (LRAs) in patients on ART and may have a potential dual role in reinvigorating exhausted T cells.
Block and lock
Dr. Chantelle Ahlenstiel (The Kirby Institute) detailed the ‘block and lock’ approach for achieving a functional cure. Her group discovered the benefit of combination shRNAs. They induced latency in a humanised mouse model by targeting both the HIV-1 promoter and the virus co-receptor CCR5 together. The resulting ‘super latent’ virus was resistant to reactivation when challenged with LRAs. CD4+ T cells remained stable following ART interruption, with a slight delay in virus rebound. The audience were enthusiastic about this approach. A final question poll indicated that 81% of the participating audience were receptive to the “block and lock” treatment approach.
While COVID-19 captured much of the world’s attention in 2020, researching an HIV cure is still an active and urgent priority with plenty of discoveries to come.
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