Immunologic and virologic response to a single dose of Kansui herbal supplement in SIV infected macaques maintaining antiretroviral therapy (ART) mediated viral suppression
Millions of HIV-infected individuals are now receiving life-saving ART, but with evidence of ongoing immune dysfunction despite treatment and the current absence of an effective cure, HIV cure has emerged as an important research strategy. This pilot non-human primate study will evaluate the tolerability and biologic effect of increasing doses of Euphorbia kansui, an inexpensive, readily available herbal supplement used in Traditional Chinese Medicine (TCM) shown to reactivate latent HIV-1 in an in vitro model. The study will test the hypothesis that Euphorbia kansui induces immune activation and viral reactivation in SIV-infected rhesus macaques maintaining antiretroviral therapy (ART)-mediated viral suppression. Extracts from the Euphorbia plant genus have long been prescribed in TCM as “kansui” to treat a variety of ailments including cancer, anasarca, and urinary retention. Several potential biologically active components from Euphorbia have been described, including ingenols, family of compounds that activate protein kinase C (PKC). PKC agonists are among the most potent latency reversing agents (LRAs) characterized to date. Recently, a synthetically modified form of ingenol (Ingenol B), has been tested in ex vivo and in non-human primate models, and found to potently reactivate latent virus with minimal toxicity. We have recently demonstrated that a commercially available kansui preparation reactivates latent HIV in Jurkat cells and in primary cells from HIV-infected ART-suppressed patients. Indeed, the level of reactivation is higher than we have observed with other well-characterized LRAs, including histone deacetylase (HDAC) inhibitors. The primary objective of this study is to evaluate the safety of Euphorbia kansui extract powder administered to rhesus macaques, and secondary endpoints will be the effects of Euphorbia kansui on markers of T cell activation and SIV persistence. Results from this study will provide preliminary data for potential future human clinical studies of Euphorbia kansui for HIV eradication.