Phase I Studies of Hypericin, the Active Compound in St. John's Wort, as an Antiretroviral Agent in HIV-Infected Adults

Background: Hypericin, the active compound in St. John's Wort, has antiretroviral 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.sup.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 daily. Measurements: Safety was assessed at weekly visits. Antiretroviral activity was assessed by changes in HIV p24 antigen level, HIV titer, HIV RNA copies, and CD4 cell counts. Results: Of the 30 patients who were enrolled, 16 discontinued treatment early because of toxic effects. Severe cutaneous phototoxicity was observed in 11 of 23 (48% [95% CI, 27% to 69%]) evaluable patients, and dose escalation could not be completed. Virologic markers and CD4 cell count did not significantly change. Conclusions: Hypericin caused significant phototoxicity and had no antiretroviral activity in the limited number of patients studied.
Hypericin has no apparent immunological effect in HIV patients, and causes significant skin sensitivity to sunlight. Hypericin is the probable active ingredient in the herbal remedy St. John's Wort, commonly used for depression. In the laboratory, hypericin has shown some antiviral activity. Researchers treated 30 HIV-infected patients with oral or intravenous hypericin. Severe phototoxicity developed in 48% of patients, and no change in CD4 white blood cell levels or other virologic markers was detected.