Valacyclovir, a drug commonly used to control the
virus that causes genital herpes, appears to reduce
the levels of HIV in patients who do not have
genital herpes, according to a study by researchers
from the National Institutes of Health, Case Western
Reserve University, Cleveland, Emory University,
Atlanta and Lima, Peru.
The study of 18 patients is the first to show that
the drug does not require the presence of herpes
simplex virus 2 (HSV-2) to suppress HIV in patients.
The researchers hope to confirm their results in a
larger study.
“These findings are very encouraging,” said senior
author Leonid Margolis, Ph.D., head of the Section
on Intercellular Interactions at the NIH’s Eunice
Kennedy Shriver National Institute of Child Health
and Human Development (NICHD). “If valacyclovir’s
effectiveness against HIV can be confirmed in a
larger cohort, it could be added to the mix of drugs
used to suppress the virus, and might prove
especially helpful in cases in which HIV has
developed resistance to other drugs.”
These results follow a 2008 study by the same
research team, which showed that acyclovir
suppresses HIV in laboratory cultures of human
tissues that were infected with various kinds of
herpes viruses. Valacyclovir is referred to as a
prodrug for acyclovir because it’s structurally
similar to acyclovir, and is converted to acyclovir
in the body. For the current study, the researchers
used valacyclovir because it remains in the blood
longer than acyclovir and so would not need to be
taken as often.
Earlier studies have shown that acyclovir reduces
HIV levels in patients coinfected with HIV and
HSV-2, the virus that causes genital herpes. However,
this effect has been attributed to the drug’s
anti-HSV-2 activity. The decrease in immune activity
results in fewer active immune cells for HIV to
infect.
In contrast, the laboratory results of the research
team indicated that the drug likely reduced HIV
levels by interfering directly with HIV’s
reproductive machinery and did not require the
presence of HSV-2.
HSV-2 chemically alters acyclovir, by attaching
chemical groups known as phosphates to it. It is
this altered form of the drug that suppresses HSV-2.
The researchers believe this form also interferes
with HIV’s ability to reproduce. In their earlier
study, the researchers found that many other kinds
of herpes viruses can also attach phosphate groups
to acyclovir. Dr. Margolis noted that these other
herpes viruses are widespread and that most people
harbor at least one of them.
“We wanted to find out whether such a mechanism
could operate in the cells of patients with HIV,”
Dr. Margolis said.
The researchers enrolled 18 HIV-infected patients in
their study, none of whom were infected with HSV-2,
and treated them with valacyclovir.
For 12 weeks, half of the enrolled patients took
valacyclovir twice a day while the other half
received a placebo. After two weeks, the placebo
group received valacyclovir while the group
originally treated with the drug switched to the
placebo.
The researchers found that when the patients took
valacyclovir, their blood HIV levels declined
significantly. Typically, HIV patients take a
cocktail of several anti-HIV drugs because a single
drug is not enough to suppress the virus. Multiple
HIV medications also hinder the virus’ ability to
develop resistance to the drugs.
The researchers conducted a genetic analysis and
found that the HIV in the study volunteers did not
develop resistance to valacyclovir. But because HIV
has a history of becoming resistant to the drugs
used to treat it, the researchers do not discount
the possibility that the virus could develop
resistance to valacyclovir with longer treatment.
Given the ability of the drug to lower HIV levels,
however, the researchers believe that valacyclovir
could one day be added to the cocktail of drugs
given to HIV-infected people.
“Larger randomized trials and cost effectiveness
analyses could be warranted to further explore the
potential of [valacyclovir] in the context of HIV-1
infection, in particular in combination with other
antivirals,” the study authors wrote.
The study, published online today in Clinical
Infectious Diseases,was supported by NIH’s Bench to
Bedside Program, which funds research teams seeking
to translate basic scientific findings into medical
practice. The first authors of this paper are
Christophe Vanpouille and Andrea Lisco, both with
NICHD. Other authors are Michael Lederman (senior
author) and Benigno Rodriguez of Case Western
Reserve University and Case Medical Center and
Hospitals; Leda Bassit, Robert Kauffman, and Raymond
F. Schinazi (senior author), Emory University School
of Medicine and Veterans Administration Medical
Center in Atlanta; and Jorge Sanchez, of The Civic
Association for Health and Education in Lima.
For more information
U.S.National Institutes of Health (NIH)
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