The research group of Wen Kang debuted data from a small, uncontrolled pilot study of the HDAC inhibitor chidamide, which is approved in China as a cancer therapy. A larger randomized controlled trial that should provide more definitive results is now ongoing. As described in detail in multiple online reports e. Human trials were initiated relatively quickly because vedolizumab is already FDA approved as treatment for ulcerative colitis and Crohn's disease. The effects were not associated with significant T cell activation or CD4 T cell death although it's important to note that this does not mean the drugs are without side effects -- those are described on their labels.
The fact that the individual who developed cancer was in the former group, despite not reinitiating ART based on viral load criteria, may raise concern that prior exposure to detectable HIV viremia was a risk factor for cancer development. The study also offered results from analyses of inflammatory biomarkers, which I've not seen described previously. Three weeks after administration of the first dose, HIV RNA was reduced to undetectable from a previous level of 7, copies per million CD4 T cells a greater than 3 log reduction. This conundrum illustrates that firm conclusions about the clinical benefits of post-treatment control compared to continuous ART cannot be drawn until post-treatment control can be induced in sufficient numbers of people to allow a randomized comparison. Lisa Chakrabarti described an investigation of potential mechanisms of HIV control in a different population: The individual is now being followed longitudinally. Updates have been fragmented since that time, occurring at various conferences, and as yet there have been no follow up publications as thorough as the original paper at least that I'm aware of -- for the sake of disclosure I should note that I chided the investigators about this situation in a public comment to the PLoS Pathogens article in Reservoir Targeting A number of presentations described novel approaches for targeting the HIV reservoir, highlighting the amount of work that is underway to try and improve upon the interventions tested to date. An interesting presentation by Sarah Joseph from the University of North Carolina at Chapel Hill outlined an effort to establish when viruses enter the latent reservoir. Advertisement The researchers cited several potential explanations: In the paper, the researchers describe an individual with HIV who exhibited undetectable viral RNA and DNA levels after receiving therapy for lymphoma including brentuximab vedotin , an anti-CD30 antibody-drug conjugate. At least two other clinical trials involving the antibody are ongoing, so additional results will be forthcoming. Whether remaining on ART would have been associated with lower risk is an unanswerable question. This time, there was no evidence of vedolizumab-induced SIV control. Human trials were initiated relatively quickly because vedolizumab is already FDA approved as treatment for ulcerative colitis and Crohn's disease. The results echo a theme that has been sounding recently in HIV cure research: A total of 12 FDA-approved chemotherapies were found to reverse HIV latency via a variety of novel pathways, suggesting new avenues for exploration beyond the current candidates, which primarily comprise HDAC inhibitors. As is emphasized in much of the coverage, the study itself should not be considered a failure because it provided a clear answer to the question it was designed to address. Joseph's data suggests that latently infected cells tend to be shorter-lived during untreated infection, with ART initiation triggering the formation of the bulk of the long-lived HIV reservoir. Unfortunately the individual died after cancer recurrence so no further investigation was possible. The effects were not associated with significant T cell activation or CD4 T cell death although it's important to note that this does not mean the drugs are without side effects -- those are described on their labels. The implication for therapeutic strategies targeting the reservoir is that there might be a window of opportunity to intervene at the time ART is started currently, almost all clinical trials involve testing candidate therapies in individuals after ART has suppressed viral load. Fauci suggested the variations in viral load levels were similar to those his group has observed in placebo recipients in prior trials, and were not indicative of any effect from vedolizumab. The results may offer support to efforts to protect virus-specific CD4 T cells from HIV infection using gene therapies that ablate CCR5 expression or otherwise attempt to protect the cells from HIV entry , an approach being pursued by researchers at the defeatHIV collaboratory. Online Post-Conference Coverage As is always the case, an array of excellent reporting has become available online since the conference. Studies published over the past year that have reached a similar conclusion include randomized controlled evaluations of a therapeutic vaccine combination and single doses of the candidate latency-reversing agent romidepsin.
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