Category: Latency reversing agents
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Today, a presentation by Ricardo Diaz at the ongoing virtual International AIDS Conference (AIDS 2020) caused a major splash in the media by reporting that one out of 30 participants in a clinical trial conducted in Brazil has experienced a lack of viral load rebound for a little over a year (64.7 weeks) after interrupting…
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One of the most widely discussed and publicized ideas for targeting the HIV reservoir is “kick and kill” or “shock and kill.” The aim is to kick dormant, latent HIV into revealing itself so the cells that contain the virus are visible to the immune system; the kill aspect involves trying to enhance the immune…
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The question of how HIV latency is typically established in long-lived memory CD4 T cells has yet to be fully resolved. One theory is that latency occurs when HIV infects a CD4 T cell that is in the process of transitioning from an activated state to a resting state, but direct evidence has been lacking.…
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The annual Conference on Retroviruses & Opportunistic Infections (CROI) took place in Seattle from February 13th-16th, offering a dizzying parade of new data. Webcasts of presentations and PDF files of posters were rapidly placed online and are accessible via the CROI website. A Fillip for Kick & Kill On the cure research front, the results…
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The 2016 Conference on Retroviruses and Opportunistic Infections (CROI) took place in Boston from February 22-25. CROI deserves kudos for pioneering comprehensive webcasting, and all sessions are available for viewing online. Results from several significant cure-related clinical trials were debuted during the meeting (links to the webcasts are in parentheses): Ole Søgaard from Aarhus University in…
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The Journal of Clinical Investigation has published a collection of reviews on HIV cure research edited by Robert Siliciano. The articles are not open access unfortunately, but a day pass for the journal’s website (which allows downloading of all PDFs) costs $10 which is relatively affordable compared to many other publishers. Recent developments in the effort…
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Several years ago, the laboratory of Robert Siliciano at Johns Hopkins University reported that the FDA-approved drug disulfiram (Antabuse) could reverse HIV latency in laboratory experiments. The discovery led Steve Deeks and colleagues to conduct a small pilot study in HIV-positive people on ART, which found that a standard dose of 500mg/day of disulfiram showed some…
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In an example of publication kismet, three recent open access articles all converge in describing a new strategy for depleting the HIV reservoir. The research involves engineering antibodies or antibody-like molecules capable of simultaneously binding two targets: the CD3 receptor, a human protein expressed on T cells, and parts of the HIV envelope (Env) protein,…
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SMAC (Second Mitochondrial-derived Activator of Caspases) mimetics are a class of compounds that have recently entered clinical trials as potential cancer treatments. The drugs antagonize anti-apoptotic proteins, thereby promoting the apoptotic death of cancer cells. Earlier this year at CROI, a poster presentation offered evidence that SMAC mimetics may also selectively promote the apoptosis of CD4…
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Two recent papers in PLoS Pathogens report that combinations of candidate latency-reversing agents can potently activate HIV production by latently infected CD4 T cells in laboratory experiments. Pairings of the PKC agonists bryostatin-1 or ingenol with the bromodomain inhibitor JQ1 were most effective, generating levels of virus production by latently infected cells similar to those…