NIAID
Topical Microbicide Research
Developing
New Tools to Protect Women from HIV/AIDS and
Other STDs
Background
HIV/AIDS, chlamydial
infection, gonorrhea and other sexually
transmitted diseases (STDs) are among the
most common diseases reported to the Centers
for Disease Control and Prevention (CDC).
More than 14 million people in the United
States get STDs each year and, at current
rates, at least one person in four will
contract an STD at some point in his or her
life. HIV infection represents a considerable
portion of the STD problem in this country
and abroad. As many as 900,000 Americans are
believed to be infected with HIV and more
than 3 million new HIV infections occurred
worldwide during 1996.
Women bear the brunt of
the HIV/STD burden. Worldwide, HIV infections
are increasing most rapidly among women, who
contract the virus primarily through
heterosexual contact. Between 1985 and 1995,
AIDS cases among women in the United States
increased nearly three-fold, and AIDS is now
the third leading cause of death among women
ages 25 to 44 in this country and the leading
cause of death among black women in this age
group.
Women are also
biologically more susceptible to certain STD
pathogens than men, and they experience more
asymptomatic STD infections. These
"silent" infections often go
untreated, and consequently, women suffer
more frequent and more severe STD
complications. For example, pelvic
inflammatory disease (PID) affects more than
1 million women in the United States each
year, and cervical cancer caused by infection
with human papillomavirus kills more than
4,000 women annually in this country.
STD infections also
commonly cause problems during pregnancy and
delivery. Low birth weight or premature birth
may complicate between one-quarter and
one-half of pregnancies in acutely infected
women. Approximately one- to two-thirds of
infants of acutely infected mothers become
infected with STD pathogens in utero
or during childbirth.
Avoiding HIV/STD
infections often is more problematic for
women than for men. Condoms provide good
protection against HIV infection and other
STDs when used correctly and consistently
during sexual intercourse. But condom use
ultimately requires the consent and
cooperation of the male partner, and women
cannot always successfully negotiate their
use. Abstinence, the only fail-safe measure
against HIV/STD infection, is not always an
option for women, since non-consensual sex is
an all-too-common reality. Just as oral
contraceptives dramatically enhanced the
ability of women to avoid unwanted pregnancy,
effective female-controlled strategies are
urgently needed to enhance the ability of
women to avoid HIV and other STDs.
Topical Microbicides
To meet the
reproductive health needs of women,
researchers increasingly have focused on the
development of virus- and bacteria-killing
gels, foams, creams or films that women can
apply intravaginally before having sex. Known
collectively as topical microbicides, these
products could give women greater control
over their risk for exposure to sexually
transmitted pathogens. Ideally, microbicides
should be unnoticeable, so they can be used
without a male partner’s knowledge, if
necessary; fast acting against HIV and a
broad range of other STD pathogens;
inexpensive; and safe for use at least one to
two times daily. In addition, microbicides
should be formulated both with and without
contraceptive properties, so women’s
reproductive decisions do not affect their
risk for HIV/STD infection.
NIAID Research
The development of
safe, effective, female-controlled topical
microbicides is a central focus of
NIAID’s HIV/STD research program. NIAID
funding for topical microbicide research has
more than doubled in recent years, increasing
from $5.3 million in 1994 to $12.2 million in
1996. The Institute's research program
reflects five goals that are necessary for
developing safe and effective topical
microbicides:
- Define the
molecular basis and chronology of the
early steps in the infectious
process.
- Define vaginal and
cervical ecology and the natural
defense mechanisms of the female
reproductive tract.
- Evaluate candidate
topical microbicides through
laboratory and pre-clinical testing
strategies.
- Establish the
safety and effectiveness of promising
compounds in controlled clinical
trials.
- Develop effective
behavioral interventions to ensure
the acceptance and use of topical
microbicides.
Central to NIAID’s
research efforts are Topical Microbicide
Program Projects at four U.S.
institutions. These multi-year projects
address a variety of basic and clinical
research questions. At the University of
California, Los Angeles, for example,
scientists are investigating protegrins,
naturally occurring protein fragments with
antibiotic properties. In laboratory
experiments, researchers assess the activity
of various protegrin formulations against HIV
and pathogens causing gonorrhea, chlamydial
infection, syphilis, genital herpes, and
trichomoniasis.
A research team at the University
of Cincinnati’s Children’s Hospital
Medical Center studies the microbicidal
potential of over-the-counter spermicides as
well as newly developed products. They also
are exploring the disease-causing mechanisms
of herpes simplex virus, chlamydia bacteria,
and HIV, to gain a better understanding of
the properties that microbicides must possess
to prevent infection with these pathogens.
At Pennsylvania
State University’s Hershey Medical
Center, NIAID-supported scientists are
developing a system to predict the safety and
effectiveness of microbicides in clinical
trials. They have developed an animal model
in which human vaginal tissue has been
grafted onto mice. Ultimately, the scientists
will use the model to determine if
experimental topical microbicides can destroy
STD pathogens without harming the vaginal
tissue.
Scientists at the University
of Pittsburgh are evaluating a number of
synthetic and naturally occurring
microbicides in laboratory and clinical
studies. Researchers recently discovered a
correlation between lactobacilli, a type of
bacteria that can occur naturally in the
vagina, and protection from gonorrhea,
bacterial vaginosis, and HIV infection.
Lactobacilli produce hydrogen peroxide and
other microbe-killing compounds. Based on
this finding, scientists developed a
lactobacillus vaginal suppository that
enables these "good bacteria" to
grow in the vagina. Clinical trials are under
way to determine whether use of these
suppositories can reduce women’s risk of
gonorrhea and bacterial vaginosis.
HIVNET Studies
In addition, NIAID is
sponsoring a clinical trial of another new
microbicidal product at Memorial Hospital in
Providence, Rhode Island, one of NIAID’s
HIV Network for Prevention Trials (HIVNET)
sites. Researchers are evaluating the safety
of an acid-buffer gel, a compound designed to
maintain the vagina’s mild acidity.
Scientists believe this acidic environment is
hostile for HIV and other sexually
transmitted organisms.
Semen is very alkaline
and raises the pH in the vagina to levels
that are more hospitable to HIV and other
sexually transmitted pathogens. Scientists
hypothesize that the acid-buffer gel should
counteract the alkalinity of semen and keep
the vaginal pH low enough to kill pathogenic
microbes. Depending on the results of this
study, further studies are planned for sites
in Asia and Africa.
NIAID also sponsors
clinical studies of over-the-counter
spermicides containing nonoxynol-9 (N-9). A
study of women sex workers in Cameroon
recently showed that contraceptive film
containing N-9 had no effect on transmission
of HIV/AIDS, gonorrhea or chlamydia infection
when provided as part of an overall HIV/STD
prevention program. Another investigation in
Kenya is testing whether a vaginal gel
containing N-9 affects the transmission of
HIV or other microbes.
NIAID, a
component of the National Institutes of
Health, supports research on AIDS,
tuberculosis and other infectious diseases as
well as allergies and immunology.
Prepared by:
Office of Communications
National Institute of Allergy and Infectious
Diseases
National Institutes of Health
Bethesda, MD 20892
Public Health
Service
U.S. Department of Health and Human Services
April 1997
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