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.

Gulick RM, McAuliffe V, Holden-Wiltse J, Crumpacker C, Liebes L, Stein DS, Meehan P, Hussey
S, Forcht J, Valentine FT
New York University Medical Center, New York, USA.

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/mm3.
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.