|Anti-Herpes Drug Does Not Reduce Risk of HIV
Infection in People with Genital Herpes Virus, Study Finds
A recently concluded clinical trial funded by the National Institute
of Allergy and Infectious Diseases (NIAID), part of the National
Institutes of Health (NIH), has found that the anti-herpes drug
acyclovir did not reduce the risk of acquiring sexually transmitted
HIV when given to men and women infected with herpes simplex virus-2
(HSV-2). Multiple studies indicate that people infected with HSV-2
are at increased risk of acquiring HIV. Researchers have speculated
that the use of acyclovir, a safe and widely used herpes drug,
could reduce HIV transmission by suppressing HSV-2 and preventing
genital sores and breaks in the skin.
Results from the Phase III clinical study, which was funded by
the National Institute of Allergy and Infectious Diseases (NIAID),
part of the National Institutes of Health (NIH), and conducted
by the NIAID-funded HIV Prevention Trials Network (HPTN), were
presented this week at the Conference on Retroviruses and Opportunistic
Infections (CROI) in Boston. The study, known as HPTN 039, is the
largest clinical study ever conducted to examine herpes suppression
as a possible means of reducing the risk of HIV transmission.
NIAID Director Anthony S. Fauci, M.D., says, "Although HPTN
039 did not yield a successful result with regard to herpes suppression
as a possible tool for HIV prevention, the concept of treating
and preventing sexually transmitted infections as a possible tool
in HIV prevention remains an important one. We will continue to
work to understand how HSV-2 and other STIs increase the risk of
HIV infection, and to develop new interventions that might play
a role in HIV prevention."
HSV-2, one of the most common sexually transmitted infections
worldwide, is especially prevalent in areas with high rates of
HIV infection. Most people who are infected with HSV-2 do not know
they have the virus because symptoms can be mild or nonexistent.
Some infected individuals have recurring sores and breaks in the
skin of the genital region, which can make it easier for these
individuals to acquire HIV. Additionally, active HSV-2 infection
attracts specific immune system cells to the genital region that
are easily infected with HIV.
People with genital herpes should be aware that this infection
increases their risk for HIV infection. It is critical all individuals
especially those with herpes know if they are infected with HIV
and take measures to protect themselves from infection with HIV
and other sexually transmitted diseases.
The HPTN 039 study was launched in October 2003 under the leadership
of Connie Celum, M.D., and Anna Wald, M.D., of the University of
Washington in Seattle. It was designed to determine if acyclovir
could reduce an HSV-2 infected person's risk of acquiring HIV infection.
The clinical trial was conducted at nine sites in Peru, South Africa,
the United States, Zambia and Zimbabwe, and involved 3,172 total
HSV-2-infected volunteers, including heterosexual women as well
as men who have sex with men. The women were enrolled at the three
African study sites, and the men at the six study sites in Peru
and the United States.
The participants received either a twice-daily, 400-milligram
(mg) dose of acyclovir tablets (800 mg total per day) — the
standard treatment regimen for suppressing genital herpes — or
placebo tablets. Throughout the course of the study, volunteers
were extensively counseled on how to avoid exposure to HIV and
were supplied with condoms.
The researchers found no evidence that the standard acyclovir
regimen prevents HIV infection among HSV-2 infected people. Specifically,
there was a 3.9 percent HIV incidence rate (75 cases) among the
1,637 participants who received acyclovir, while there was a 3.3
percent HIV incidence rate (64 cases) among the 1,640 participants
who received placebo.
"The difference in HIV rates in the acyclovir and placebo
group is not statistically significant, indicating that when acyclovir
is used twice-daily at the 400 mg dose, the drug does not prevent
HSV-2-infected individuals from becoming infected with HIV," says
Dr. Celum. "More research is needed to understand ways to
reduce HIV susceptibility among persons with HSV-2."
The study did, however, provide additional evidence that acyclovir
reduces the occurrence of genital sores: the volunteers who received
acyclovir had a 37 percent decrease in genital ulcer incidence
and a significantly lower proportion of ulcers due to HSV-2.
"The study answered the scientific questions it was designed
to answer," says Dr. Wald. "The sites were able to recruit
and retain a large number of volunteers, who maintained a high
level of adherence to the twice-daily drug regimen. While we are
disappointed with the results, the study was well-conducted and
provides a clear answer about using acyclovir to reduce the risk
of becoming HIV-infected."
The study participants have been informed of the findings and
are being counseled on the continued need to avoid HIV exposure.
Volunteers who became infected with HIV during the trial have been
referred for appropriate medical care and treatment.
The HPTN is led by Family Health International in Research Triangle
Park, N.C., HPTN clinical laboratory located at Johns Hopkins University
in Baltimore, and the Statistical Center for HIV/AIDS Research
and Prevention at the Fred Hutchinson Cancer Research Center in
For more information about the HPTN 039 clinical study, see http://www3.niaid.nih.gov/news/QA/hptn039_QA.htm.
NIAID is a component of the National Institutes of Health. NIAID
supports basic and applied research to prevent, diagnose and treat
infectious diseases such as HIV/AIDS and other sexually transmitted
infections, influenza, tuberculosis, malaria and illness from potential
agents of bioterrorism. NIAID also supports research on basic immunology,
transplantation and immune-related disorders, including autoimmune
diseases, asthma and allergies.
News releases, fact sheets and other NIAID-related materials
are available on the NIAID Web site at http://www.niaid.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.