Category: HDAC inhibitors
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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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The primary barrier to curing HIV infection is the persistence of the virus in a latent form in long-lived resting memory CD4 T cells. The number of latently infected resting memory CD4 T cells in a typical individual on ART is estimated to be in the range of 1-60 million. An important strand of HIV…
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Results from a phase I trial of the candidate latency reversing agent panobinostat were published last year in The Lancet HIV (see blog post from November 2014). The paper notes that in an exploratory analysis, a subset of four (out of a total of 15) participants experienced a significant decline in cell-associated HIV DNA levels of…
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At CROI last year, Gregory Laird presented results from a laboratory study that tested the activity of several candidate HIV latency-reversing agents (LRAs) on latently infected CD4 T cells isolated from HIV-positive individuals on ART. The results were disappointing: only one LRA showed a very modest effect on HIV gene expression and none induced significant…
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The 2015 Conference on Retroviruses and Opportunistic Infections (CROI) took place in Seattle from February 23rd to the 26th. The major news that emerged from the meeting was the extremely high degree of protection from HIV infection obtained with pre-exposure prophylaxis in two studies, PROUD and IPERGAY. On the vaccine and cure fronts nothing was…
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Results from the second clinical trial to test the HDAC inhibitor vorinostat as a latency-reversing agent, first presented at CROI 2013, have now been published in the open access journal PLoS Pathogens. The study design differed from the first trial, involving a longer 14-day dosing period. The results are broadly consistent, with a significant increase in…
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In the spring of 2013, a wildly inaccurate Daily Telegraph story about HIV cure research claiming “there will be a breakthrough in finding a cure for HIV within months” was amplified around the Internet, understandably receiving a massive amount of attention and interest. To their credit, the researchers whose work prompted the piece published a…
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Two recent papers address the potential of broadly neutralizing antibodies (bNAbs) to decrease HIV rebound from persistent reservoirs. In the journal Cell, Ariel Halper-Stromberg and colleagues report the results of experiments conducted in the humanized mouse model with a “tri-mix” of three monoclonal bNAbs: 3BNC117, 10-1074, and PG16. When administered as post-exposure prophylaxis four days…
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The persistence of a latent form of HIV integrated into the genome of long-lived cells, particularly memory CD4 T cells, is considered the most significant barrier to curing the infection. A key element of cure research is the pursuit of strategies capable of inducing latent HIV to replicate, with the aim of causing the death…
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At a symposium on cure research held prior to the International AIDS Conference in 2012, Robert Siliciano presented new data suggesting that the amount of replication-competent latent HIV that persists in the face of antiretroviral therapy (ART) may be greater than previously appreciated (the video and powerpoint from Siliciano’s talk are available on the symposium…