1. Safety and effect of an extract from Ganoderma lucidum (Reishi) on NK cell numbers in HIV+ individuals not taking antiretroviral therapy. JT Leonard 1, I Majd 1, JP Kassermann 1, CA Wenner 1 1 Bastyr University, Kenmore WA BACKGROUND Reishi is an immunomodulatory botanical used in Traditional Chinese Medicine. Triterpenes from Reishi have shown activity against HIV-1 protease in vitro, and Reishi has been shown to increase total lymphocytes, CD4+ cells, NK cell counts and activity in cancer patients taking Reishi orally. This study investigated the safety of oral Reishi supplementation in HIV+ individuals and followed trends in HIV viral load and lymphocyte subset counts. METHODS 10 HIV+ individuals with CD4+ cell counts >200 cells/μl and plasma HIV-1 RNA levels <50,000 not currently taking antiretroviral medications were enrolled in this 4-month dose escalation study. After a baseline blood draw, subjects were given the following daily Reishi doses for one month each sequentially: 2 grams, 5 grams, and 10 grams. Plasma chemistries, HIV-1 RNA levels, CD4/CD8, NK cell counts and adverse event questionnaires were performed after each dosing month, and at a one-month washout. CONCLUSIONS Reishi supplementation is safe and well-tolerated in HIV+ individuals not taking antiretroviral therapy. Further studies are warranted to determine which subset of NK cells are increased and whether this increase confers any advantage either in terms of delaying time to initiating antiretroviral therapy in treatment naïve individuals or in restoring NK cell populations in patients under antiretroviral treatment. ACKNOWLEDGEMENTS We would like to thank John Seleen of JHS Naturals, Inc. for donating the Reishi capsules used in this study. FUNDING SUPPORT PROVIDED BY NIH NATIONAL CENTER FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE RESULTS Reishi was well-tolerated with no serious adverse events reported and no grade 3 or 4 laboratory adverse events from the study medication. Mild GI side effects were experienced by two subjects and were self- limiting. No significant trends in laboratory chemistries, CD4%, or log viral load were noted. There was a significant increase in the percentage of CD16+ NK cells, which peaked at 5 grams/day and returned to baseline during the washout phase. (figure 1) Two subjects experienced significant decreases in viral load at 5 grams/day, while three other subjects trended toward higher CD4% while on Reishi. (figures 2 and 3) Photograph of Ganoderma lucidum, aka Reishi mushroom Figure 1: Effect of 1 month daily Rieshi treatment (5 gm) on percent CD16+CD3- cells in blood of HIV+ volunteers PURPOSE Immune therapies aimed at stimulating the anti-viral immune response, such as IL-2 and IL-12 therapy, also have resulted in stimulation of viral replication, resulting in higher viral load in the serum despite sometimes improved CD4 counts. In addition, previous studies with these immunomodulating substances in HIV+ patients have shown that they carry significant side effect profiles. The aim of this study was to determine if a natural immunomodulating substance, Ganoderma lucidum, would be well-tolerated in HIV+ subjects not taking anti-retroviral therapy. Figure 2: Effect of increasing Reishi doses on HIV viral loads of study volunteers Figure 3: Effect of increasing Reishi doses on percent CD4+ T cells in blood of study volunteers