Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults - AIDS clinical trials group protocols 150 and 258

Background: Hypericin, the active compound in St. John's Wort, has antiretr oviral activity in vitro. Many HIV-infected persons use St. John's wort. Objective: To evaluate the safety and antiretroviral activity of hypericin in HIV-infected patients. Design: Phase I study. Setting: Four clinical research units. Patients: 30 HIV-infected patients with CD4 counts less than 350 cells/mm(3 ). Intervention: Intravenous hypericin, 0.25 or 0.5 mg/kg of body weight twice weekly or 0.25 mg/kg three times weekly, or oral hypericin, 0.5 mg/kg dail y. Measurements: Safety was assessed at weekly visits. Antiretroviral activity was assessed by changes in HIV p24 antigen level, HIV titer, HIV RNA copie s, and CD4 cell counts. Results: Of the 30 patients who were enrolled, 16 discontinued treatment ea rly because of toxic effects. Severe cutaneous phototoxicity was observed i n 11 of 23 (48% [95% CI, 27% to 69%]) evaluable patients, and dose escalati on could not be completed. Virologic markers and CD4 cell count did not sig nificantly change. Conclusions: Hypericin caused significant phototoxicity and had no antiretr oviral activity in the limited number of patients studied.