Author Interviews, HIV, PLoS, UC Davis / 31.07.2015
Cancer Drug Can Activate HIV Reservoirs To Target For Eradication
MedicalResearch.com Interview with:
Dr. Satya Dandekar PhD
Professor and Chair
Department of Medical Microbiology and Immunology
UC Davis
Medical Research: What is the background for this study? What are the main findings?
Dr. Dandekar: Current anti-retroviral therapy is effective in suppressing HIV replication and enhancing immune functions in HIV infected individuals. However, it fails to eradicate the latent HIV reservoirs. Therapy interruption leads to a rapid viral rebound in these patients. Eradication of latent HIV reservoirs is essential to achieve HIV cure. A “shock and kill” strategy for HIV cure has been proposed that involves reactivation of latent viral reservoirs using latency reversal agents (LRA) and eradication by the immune response. This highlights the need to identify potent LRAs to optimally activate latent HIV reservoirs so that immune surveillance and clearance mechanisms can be effectively engaged in the process of viral eradication. We have found that ingenol-3-angelate (PEP005), an anti-cancer drug can effectively reactivate latent HIV. It is a protein kinase C agonist that activates NF-kB and stimulates HIV expression. In combination with another compound, JQ1, a previously known p-TEFb agonist, the efficacy of PEP005 for HIV reactivation is markedly increased. In addition, ingenol-3-angelate decreases the expression of HIV co-receptors on immune cells, which potentially will help preventing further spread of the virus. The use of ingenol-3-angelate in combination with other latency reversal agents provides an excellent opportunity to optimally activate latent HIV reservoirs and target them for eradication.
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