Hypericin and AIDS
Many people infected with the human immunodeficiency virus (HIV)
have incorporated St. John's wort (Hypericum perforatum
L., Clusiaceae) into their self-care regimens, based on laboratory
evidence that hypericin and pseudohypericin are active against
retroviruses such as HIV (Meruelo et al., 1988; Lavie et
al., 1990). According to reports about earlier clinical research,
St. John's wort helped to improve outlook, reduce fatigue, and
enhance well-being for people with HIV, but it was unclear whether
the improvements were related to antidepressant effects or to
direct antiviral activity (Bergner, 1990).
To investigate the safety and antiretroviral activity of hypericin
in a clinical setting, a group of American researchers conducted
a phase I study of 30 HIV-infected people with CD4 counts lower
than 350 cells/mm3 (Gulick et al., 1999). Phase
I studies are primarily concerned with assessing the safety of
a substance and evaluating side effects that occur as dosage is
increased.
This small study, which employed oral and injectable treatment
with synthetic hypericin, yielded disappointing results. Not only
did the pharmaceutical hypericin demonstrate no antiretroviral
activity, it caused severe phototoxicity in 48 percent of the
participants. Sixteen of the 30 subjects (53 percent) dropped
out of the study early because of side effects. Almost all of
the participants taking either oral or injectable hypericin experienced
some degree of phototoxicity, which caused a painful red rash
in areas exposed to light.
The investigators speculated that the lack of anti-retroviral
activity could be attributed to the fact that the high incidence
of side effects made it impossible for them to achieve sustained
blood levels of hypericin sufficient to inactivate the virus.
It is important to note that since this study utilized a synthetic
hypericin preparation, its results cannot necessarily be extrapolated
to St. John's wort standardized extract or whole plant preparations.
For the study, the participants were divided into four groups.
Three of the groups were treated with intravenous hypericin (0.25
or 0.5 mg/kg twice weekly or 0.25 mg/kg three times weekly) and
one received oral hypericin (0.5 mg/kg daily). The antiretroviral
activity of the synthetic hypericin was assessed by measuring
changes in CD4 cell counts, HIV p24 antigen level, virus titer,
and HIV RNA copies. There were no detectable changes in any of
these parameters. Adverse effects were evaluated weekly and graded
according to a four-point scale, with grade 1 representing the
mildest adverse reaction and grade 4 representing the most severe
reaction. Grade 3 phototoxicity, which was observed in 48 percent
of the study subjects, was defined as "intolerable erythema
or numbness (or both), temperature sensitivity, and pain despite
long-term analgesic therapy." No grade 4 phototoxicity was
reported.
The investigators suggested that even though the synthetic hypericin
proved too toxic to allow assessment of its clinical value in
this study, other applications might hold more promise. "The
potent antiviral activity of hypericin in vitro has led to its
use in the ex vivo treatment of blood components," they noted.
"This approach avoids phototoxicity and uses the well-described
enhancement of the antiviral effect of hypericin by light."
- Evelyn Leigh
[Bergner P. Hypericum and AIDS. Medical Herbalism 1990;
2(1): 1-6.
Gulick RM, McAuliffe V, Holden-Wiltse J, Crumpacker C, Liebes
L, Stein DS, Meehan P, Hussey S, Forcht J, Valentine FT. Phase
I studies of hypericin, the active compound in St. John's wort,
as an antiretroviral agent in HIV-infected adults. Annals of
Internal Medicine 1999; 130(6): 510-514.
Lavie G, Mazur Y, Lavie D, Levin B, Ittah Y, Meruelo D. Hypericin
as an antiretroviral agent. Annals NY Acad Sci 1990; 616:
556-562.
Meruelo D, Lavie G, Lavie D. Therapeutic agents with dramatic
antiretroviral activity and little toxicity at effective doses:
Aromatic polycyclic diones hypericin and pseudohypericin. PNAS
1988; 85: 5230-5234.]
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