In response to the global AIDS epidemic and heightened concern about other STD infections, scientists are intensifying the search for technologies to prevent these diseases--especially methods that women can use. The new products for women--vaginal microbicides--are not yet available, but some are being tested in a number of countries.

Microbicides can use one or more of the following mechanisms of action to combat infection: They can block infection by creating a barrier between the pathogen and the vagina. They can kill or otherwise immobilize pathogens. Or they can prevent a virus from replicating once it has infected the cells that line the vaginal wall. Vaginal microbicides will probably be produced in many forms--gels, creams, suppositories, film, sponges and vaginal rings.

Because STDs are caused by different types of pathogens, a microbicide that works against one will not necessarily protect against another. So scientists are trying to develop products that will be effective against a wide range of pathogens, including HIV. The challenge is to develop products that are highly effective against infectious organisms but low in toxicity and nonirritating during repeated vaginal use.

Some microbicides being investigated will prevent pregnancy as well as protect against STDs, while others will not. The development of a noncontraceptive microbicide will be important for women who have an HIV-positive partner but who want to have children.

Many Novel Approaches Are Being Explored in the Development of Microbicides

At least 60 vaginal microbicidal products are in various stages of development. Some are based on existing products used in new ways or new combinations; others are based on completely new compounds.

• Antibodies, one of the body's main defense systems, are the basis for vaccine technology. Scientists have found ways to isolate the antibodies that counteract HIV and other infections and to mass-produce them. These technologies raise the possibility of delivering antibodies directly to the vagina, allowing them to combat pathogens before infection occurs.
• Detergents and surfactants disrupt the outer membranes of cells and the outer shell of viruses. Nonoxynol-9 is a detergent; another detergent that is used as a spermicide (octoxynol-9) is also being explored as a potential microbicide, as are compounds that are used in shampoo, toothpaste and contact lens solution.
• Gels that coat the vagina may prevent HIV from entering the cells of the vaginal lining. One promising gel is an inexpensive substance derived from seaweed.
• Peptides are small protein molecules that line every surface of the body--eyes, skin, lungs, tongue and intestinal tract--and kill bacteria within minutes of contact. If applied in concentrated quantities at the site of potential infection, peptides may kill off pathogens before they cause infection.
• pH regulators maintain the natural acidity (pH level) of the vagina, making it inhospitable to HIV. (The virus cannot live in the normal acidity of the healthy vagina; however, semen is alkaline, and the vagina becomes more alkaline during intercourse, allowing HIV to survive.) One formulation under investigation also creates a physical barrier that helps block the passage of pathogens into the cells of the vagina and cervix.
• Antiretroviral products interrupt the replication of a virus once it enters a cell. Many antiretroviral drugs initially explored as potential AIDS therapies were abandoned because they were not easily absorbed into the bloodstream. But these compounds might work well in vaginal microbicides, because they could be applied to the skin and would not have to be absorbed systemically.

Testing the Efficacy and Safety of Microbicides Will Take Many Years

All new drug formulations are subjected to lengthy (and therefore costly) laboratory, animal and human trials before the Food and Drug Administration (FDA) approves them for use in the United States. Testing involves a number of carefully phased stages.

Once the FDA has granted approval of a drug, its manufacture and labeling, the new product becomes available for physicians to prescribe or for sale over the counter, without a prescription. But the manufacturers must continue to submit periodic reports to the FDA, including any reports of adverse reactions.

Only one in every 1,000 compounds that start off in laboratory testing make it to clinical trials, and only one in five of those are eventually approved for marketing. The rigorousness of the process largely explains why it typically takes so long and costs so much to bring a new pharmaceutical product onto the market.

Many scientific questions about microbicides are still to be resolved. These include the potential of a microbicide developed for vaginal use to be adapted for rectal use (which would make the product useful both for women and for men who have sex with men), how long particular products will be effective once applied and their safety over long periods of repeated use.

Although not all the leads being pursued will end up as microbicidal products, experts agree that many have the potential to become useful, effective and safe methods of reducing STD infection. The ideal would be a situation in which different formulations of microbicides were available for use in different phases and contexts of women's and men's sexual lives, as is now the case with contraceptive methods.

For more complete info on this article, please visit The Alan Guttmacher Institute.