Monkeys protected from HIV-like virus using vaginal gel
NIH release
November 3, 2005
Experiments in female monkeys have for the first time shown that when used
in combination, vaginal gels known as microbicides can protect against an HIV-like
virus. The research, funded largely by the National Institute of Allergy and
Infectious Diseases (NIAID), one of the National Institutes of Health (NIH),
suggests that similar combination microbicides could potentially provide a safe,
effective and practical way to prevent HIV transmission to women, according to
study investigators.
The study, published online October 30 in the journal Nature, represents
the first successful testing of combination microbicides in a primate model.
Women make up nearly half of all people living with HIV worldwide, and a vast
majority of new cases of HIV infection in women result from heterosexual intercourse. This
study demonstrates that combination microbicides are feasible, says NIAID Director
Anthony S. Fauci, M.D. We need to build on these promising animal studies and
move toward establishing the safety and effectiveness of combination microbicides
in women.
Vaginal microbicides include creams, gels or other substances that could be
applied topically to prevent the transmission of HIV and other sexually transmitted
infections. At least five different candidate microbicides currently are being
evaluated in large clinical trials, but no microbicide has yet been approved
for human use.
The Nature study was led by John P. Moore, Ph.D., of the Weill Medical
College of Cornell University in New York City, and Ronald S. Veazey, D.V.M.,
Ph.D., of the Tulane National Primate Research Center in Covington, LA. For the
experiments, they used simian-human immunodeficiency virus (SHIV), a hybrid virus
made in the laboratory from HIV and its cousin, SIV, which infects only non-human
primates. The researchers tested three microbicide gels alone and in combination.
Two contained small molecules and the third featured a modified assembly of protein
building blocks; each of the three was designed to block SHIV from entering specific
cells in the vaginal area and thereby prevent the virus from invading the monkeys
body. The two small molecules were provided by Bristol Myers Squibb Inc. (BMS),
based in Wallingford, CT, and Merck Research Laboratories, headquartered in Rahway,
NJ. Weill Cornell Medical College supplied the third compound, which is similar
to the approved anti-HIV drug Enfuvirtide (Fuzeon).
During testing, researchers sedated the monkeys, applied the experimental gels,
and exposed the animals to a single virus dose 30 minutes to 12 hours later.
Each of the three microbicide gels provided protection against the virus when
used alone. Moreover, of the 20 monkeys given the BMS and Merck microbicides
in combination, 16 were protected from infection. All three monkeys given the
triple combination of microbicides remained virus-free. None of the monkeys appeared
to experience vaginal irritation or inflammation from the experimental gels.
Of note, the researchers found that the Merck and BMS compounds could be applied
up to six hours prior to exposure to the virus and still offer protection.
This is encouraging for the development of a microbicide for use in the real
world, says Dr. Moore.
Jim Turpin, Ph.D., of NIAIDs Topical Microbicide Team, says, Just as weve
seen with combination antiviral medicines, this study shows that if you can hit
two or more different targets of the virus, the greater the effectiveness of
the product.
The research team deliberately chose the three specific test compounds for several
reasons.
We felt these inhibitors were likely to be fairly safe, says Dr. Veazey. Similar
compounds have a good safety record in humans thus far.
The small molecules were also chosen for their potential as a cost-effective
product for women. A microbicide has to be safe, effective, and socially acceptable,
but the cost of its active ingredients will also be an issue, says Dr. Moore. We
didnt want to work with inhibitors that could not be made in large quantities
or would be produced only at great expense. Instead, we selected compounds similar
to those now being developed as antiviral drugs for treating HIV-1 infection
because we thought they might be practical to develop as a microbicide.
Although encouraged by their findings, Dr. Moore notes, Animal studies are
an important step, but there is much more work that needs to be done before a
product can be made available for human use. Small clinical trials to determine
safety and optimal dosage will be the next stage.
News releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at http://www.niaid.nih.gov.
NIAID is a component of the National Institutes of Health, an agency of
the U.S. Department of Health and Human Services. 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 transplantation and immune-related illnesses, including autoimmune
disorders, asthma and allergies.
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 http://www.nih.gov.
Reference: RS Veazey et al. Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion. Nature DOI:10.1038/nature04055 (2005)
This is a NIH news release.
