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“Second-generation”
Microbicide Research Under Way
Scientists at the Population Council’s
Center for Biomedical Research are developing and testing several
second-generation microbicide formulations, even as the Council’s first
candidate microbicide, Carraguard®, enters the final stretch
of its Phase 3 clinical trial.
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About Carraguard
Carraguard is made of
carrageenan, derived from seaweed. If a carrageenan-based
product is found to be effective, seaweed’s abundance should
help make the microbicide affordable worldwide.
Council research has
demonstrated that Carraguard is effective in preventing the
transmission of HIV in the laboratory.
Carraguard has been proven to
be stable at a range of temperatures, which is important in
ensuring that it does not degrade over time.
 Carrageenan
has been used for decades as a thickening agent in many
products, including infant formula, soups, and ice cream.
Carraguard is a highly charged
molecule that binds to viruses or to cells in the vagina.
Scientists hypothesize that this nonspecific binding forms a
protective coating that prevents the virus from entering the
bloodstream. |
A microbicide is a product in a gel or
similar form that would reduce transmission of HIV—and possibly other
sexually transmitted infections—when used before intercourse. Such
products would give women a means to protect themselves against HIV—an
option that many women, whose health and lives often depend on
persuading their partners to use condoms, do not currently have.
The Council is conducting the clinical
trial of Carraguard, which involves more than 6,000 women in South
Africa. Data collection for this trial, intended to determine how well
Carraguard prevents HIV transmission, is expected to conclude in March
2007. The Carraguard trial is likely to be the first of the
first-generation microbicide trials to complete data analysis.The Council’s next-generation microbicide
candidates, which show considerable promise in laboratory testing,
combine Carraguard with other compounds. The new formulations have been
shown to be nontoxic to vaginal epithelial cells in rabbits and stable
in a range of temperatures. The extensive preclinical testing performed
on these combination products will facilitate regulatory agency
approvals, particularly in light of Carraguard’s excellent safety
profile.
“The additional mechanisms of action these
new formulations offer are promising,” says Elof Johansson, vice
president of the Council’s Center for Biomedical Research. “One
formulation has the potential to block the herpes simplex virus, in
addition to HIV. Another, PC-815, employs two different mechanisms of
action to block HIV infection, so if the virus isn’t blocked from
entering cells, it is inactivated once inside.” Laboratory tests have
also shown the anti-HIV drug MIV-150 to be highly active against HIV
and, when combined with Carraguard, to be stable and safe when tested in
animals.One second-generation formulation is
already in the first stage of clinical testing. This
Carraguard-levonorgestrel combination, or Carra/LNG, is aimed at
providing protection against both HIV and pregnancy. (The initial
Carraguard formulation is noncontraceptive.) Levonorgestrel is a
synthetic progestin that has been proven safe and effective as a
contraceptive in pills, implants, and intrauterine systems, including
several products developed by Council scientists.
Two small Phase 1 safety studies are
planned for PC-815, one with HIV-negative women and one with
HIV-positive women. The study with HIV-positive women will also collect
data on whether exposure to the microbicide gel reduces the amount of
active virus in the vagina.
The Swedish Ministry of Foreign Affairs has
announced the donation of 15 million Kronor (more than US$2 million) to
the Population Council for the development of PC-815. The Ministry has
been an early and strong supporter of the Population Council’s
microbicide program.
“Sweden, with its longstanding focus on
prevention measures, considers your work to be excellent,” wrote Carin
Jamtin, then Minister for International Development Cooperation. “We . .
. understand the need for stable and sustainable financing when it comes
to research, which by nature is a long-term venture and often [very
costly].”
In addition to
Sweden, support for the Council’s microbicides research has come from
The Andrew W. Mellon Foundation, the Bill and Melinda Gates Foundation,
the National Institute of Allergy and Infectious Diseases (NIAID), the
National Institute of Child Health and Human Development (NICHD), the
Rockefeller Foundation, and the United States Agency for International
Development (USAID).
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