ACYCLOVIR RESISTANT HERPES: NEW TREATMENT OPTION?

Three anecdotal case reports have recently come to our
attention about a potentially effective treatment for acyclovir-
resistant herpes. The treatment, an ophthalmic (eye) solution
called trifluridine (also called Viroptic, or
trifluorothymidine), is available by prescription. It is
currently used to treat patients with herpes simplex keratitis,
an infection of the cornea of the eye.

The only published report on trifluridine treatment of
acyclovir-resistant herpes in a person with HIV infection was
presented at the Sixth International Conference on AIDS in San
Francisco in June, 1990 [Doherty and others, abstract Th.B. 446].
This patient first had acyclovir-resistant herpes lesions which
responded to foscarnet. However, a subsequent lesion was
resistant to both acyclovir and foscarnet. Two other topical
treatments (idoxuridine cream; interferon gel alone) were tried
but failed in this patient before she responded to the
combination of trifluridine and interferon with "considerable but
incomplete healing."

Two other cases were discussed by Harold Kessler, M. D.,
from Rush-Presbyterian St. Luke's Medical Center in Chicago, at
the recent meeting of the AIDS Clinical Trials Group (ACTG) in
Washington, D. C. (The ACTG is a research program of the National
Institute of Allergy and Infectious Diseases of the National
Institutes of Health; it is the group which conducts the bulk of
the Federally sponsored AIDS clinical research in this country.)
Dr. Kessler emphasized that there is no proof that trifluridine
is effective in acyclovir-resistant herpes, because there have
been no studies of this treatment. In addition, he knows of a
total of only four episodes of herpes in three patients who were
treated with this drug. However, he agreed that this information
should be made available to patients and physicians before the
completion of a controlled study since there are few alternative
treatments currently available to people with herpes lesions that
are resistant to both acyclovir and foscarnet.

Dr. Kessler described applying a thin film of the solution
over a well-cleansed lesion. He then covered the lesion with a
thin layer of Polysporin ointment to keep the solution in contact
with the lesion. Gauze was placed over the lesion. The
medication and dressing were changed three times a day. One
patient (with a lesion of three by four centimeters) responded in
four to five weeks. This patient relapsed with a lesion that was
next to the original one. The second lesion healed within two
weeks with treatment with trifluridine. A second patient was
treated at another medical center and had a complete response in
two weeks.

Dr. Kessler emphasized that this treatment is not a cure for
herpes simplex infections. New lesions will occur after
treatment with any anti-herpes drug. However, new lesions may be
susceptible to acyclovir and/or foscarnet.

An open-label prospective study of this drug is being
designed for people with chronic cutaneous herpes which is
suspected of being acyclovir resistant. In the meantime, Dr.
Kessler has requested that physicians trying trifluridine send
viral isolates for acyclovir and foscarnet resistance testing to
his laboratory in Chicago so that the effectiveness of
trifluridine can be assessed before the official study is under
way. Physicians can reach Dr. Kessler at 312/942-5865 (Division
of Infectious Diseases, Rush-Presbyterian St. Luke's Medical
Center, Chicago).