Several independent research groups have identified ingenol esters, compounds derived from the tropical shrub Euphorbia tirucalli, as potent activators of latent HIV. Papers published in the journals Virology and AIDS report that a specific semi-synthetic ingenol ester named 3-caproyl-ingenol (ING B) demonstrates the greatest promise and may represent a candidate for clinical trials. The compound appears to work by targeting the protein kinase C (PKC) pathway, similar to another known latency-reversing candidate prostratin but with less evidence of toxicity. At the International Workshop on HIV Persistence last December, Lucio Gama from Johns Hopkins University presented results from ING B studies in SIV-infected macaques indicating that the drug was safe to administer and showed activity against latent virus. Gama also offered a glimpse at preliminary data from the laboratory of Robert Siliciano suggesting that ING B potently activated latent HIV in CD4 T cells isolated from HIV-positive individuals on ART. Additional analyses are ongoing with a view to assessing if ING B can safely be advanced into human clinical trials, and whether additional modifications to the compound might enhance safety and activity.
Richard Jefferys is the coordinator of the Michael Palm HIV Basic Science, Vaccines & Prevention Project Weblog at the Treatment Action Group (TAG). The original blog post may be viewed here.