A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: A phase I/II trial

Lentinan is a beta 1 --> 3 glucan isolated from Lentinus edodes (Shiitake m ushroom) which has immune modulating properties. We have conducted two phas e I/II placebo-controlled trials on a total of 98 patients. In one study at the San Francisco General Hospital (SFGH), ten patients each were administ ered 2, 5, or 10 mg of lentinan or placebo iv once a week for eight weeks. In the second study at the Community Research Initiative in New York (CRI), two groups of 20 patients each were administered 1 or 5 mg of lentinan iv twice a week for 12 weeks, and ten patients were administered placebo (vehi cle containing mannitol plus dextran 40) iv twice a week. Entry criteria we re an HIV positive test, CD4 levels of 200-500 cells, age 18-60 years, and without current opportunistic infections. This study confirms, in Caucasian subjects also, the good tolerability of lentinan observed in Japanese canc er patients. Side effects were mainly mild, especially when infusion was carried out ove r a 30-minute period. In the SFGH study, where administration was over a te n minute period, there were nine side effects severe enough to be reported to the FDA tone case each of anaphylactoid reaction, back pain, leg pain, d epression, rigor, fever, chills, granulocytopenia and elevated liver enzyme s) and there were four patients who discontinued therapy because of side ef fects. In the CRT study, where infusion was over a 30-minute period, there were no side effects reportable to the FDA and there were four dropouts due to side effects or personal preference. Most side effects resolved promptl y after the discontinuation of medication, and all of them were relieved wi thin 24 hours. Patient-a in the study have shown a trend toward increases i n CD4 cells and in some patients neutrophil activity. Because of the small numbers, these values do not have statistical significance. Inasmuch as no side effects such as anemia, leukopenia, pancreatitis or neu ropathy were seen, and in view of the positive effects of lentinan on certa in surrogate markers (recognizing that these were small studies), we recomm ended a long-term clinical trial of lentinan in combination with didanosine (ddI) or zidovudine in HIV positive patients. Most patients in these trial s did not have measurable p24 levels. In the CRI trials of ten patients wit h elevated p24 levels, eight on lentinan and two on placebo had decreased p 24 levels. Of these decreases, those with lentinan and one with placebo wer e marked. These results were provocative and needed confirmation. Subsequent to this study, a trial of lentinan in combination with didanosin e (ddI) showed a mean increase of 142 CD4 cells/mm(3) over a twelve month p eriod, in contrast to a decrease in CD4 cells in patients on ddI alone (Gor don et al. 1995).