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

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

Roy M. Gulick, MD, MPH;
Vincent McAuliffe, MD;
Jeanne Holden-Wiltse, MPH;
Clyde Crumpacker, MD;
Leonard Liebes, PhD;
Daniel S. Stein, MD;
Patricia Meehan, PhD;
Sheila Hussey, RN;
Janet Forcht, RN;
Fred T. Valentine, MD; and
for the AIDS Clinical Trials Group 150 and 258 Protocol Teams

From New York University Medical Center, New York, New York; Harvard University School of Public Health and the AIDS Clinical Trial Unit, Beth Israel Hospital, Boston, Massachusetts; and National Institutes of Health, Rockville, Maryland.

Abstract

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.

Article and Author Information

Acknowledgments: The authors thank Howard Hochster, MD, and Sandra Mendoza, MS (New York University, New York, New York), for pharmacology; Michael Hamrell, PhD (Division of AIDS, Bethesda, MD), Dawn Bell, Pamela Clax, Richel Stowell, and Thomas Nevin (Adult ACTG Operations Center, Social & Scientific Systems, Inc., Rockville, Maryland) for protocol support; Kenneth Wood (Frontier Science and Technology Research Foundation, Buffalo, New York) for data management; Judith Feinberg, MD, and Louis Grue, RN (Johns Hopkins University, Baltimore, Maryland), and Alejo Erice, MD (University of Minnesota), for clinical support; VimRx Pharmaceuticals, Wilmington, Delaware, for providing the study drug; and the patient volunteers.
Grant Support: By grants U01-AI 27665, P30-AI 27742, and M01-RR 0096. The study was sponsored by the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases.
Requests for Reprints: Roy Gulick, MD, Cornell Clinical Trials Unit, Box 566, 525 East 68th Street, New York, NY 10011.
Current Author Addresses: Dr. Gulick: Cornell Clinical Trials Unit, Box 566, 525 East 68th Street, New York, NY 10011.
Drs. McAuliffe, Liebe, and Valentine and Ms. Forcht: New York University School of Medicine, 550 First Avenue, New York, NY 10016.
Ms. Holden-Wiltse: Statistical and Data Analysis Center, Harvard University School of Public Health, Frontier Science, Boston, MA 02215.
Dr. Crumpacker and Ms. Hussey: AIDS Clinical Trials Unit, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.
Dr. Stein: Glaxo-Wellcome, Inc., 5 Moore Drive, Research Triangle Park, NC 27709
Dr. Meehan: Biomedical Research, Inc., Boston, MA.