Looking for a Few Good Microbicides Candidates

Until recently, microbicide discovery was a by-product of the search for anti-HIV drugs. Early in the search for microbicides, for example, attention focused on detergents because of their ability to disrupt HIV’s coat. Most such easily testable candidates, however, failed as microbicides. Now that scientists know more about HIV’s life cycle,
they are beginning to identify multiple points at which the virus could be stopped.

Ideally, a microbicide should be:
• Colorless and odorless
• Inexpensive to manufacture and purchase
• Safe to use more than once a day and for long periods of time
• Effective against multiple STDs, including HIV/AIDS
• Fast-acting, long-lasting, and non-irritating
• Undetectable to either partner
• Available in contraceptive and non-contraceptive forms
• Available without a prescription

In theory, creating an effective topical microbicide should be easy. Simply identify chemicals that kill disease-causing organisms, blend the chemicals with an inert gel or foam, and place it in the vagina. Experience, however, has shown that the simple approach may not work.

The Research Pipeline 
Like a new drug or vaccine, topical microbicide development will follow a pathway—the research pipeline—from basic research to commercial production. The key points along the pipeline are basic research, product formulation and preclinical testing, and clinical testing.

Basic biomedical research sets the foundations for later-stage research. In basic research on topical microbicides, scientists are:
• Determining exactly how HIV and other STD-causing organisms gain entry into cells and spread from cell to cell
• Characterizing the bacterial ecosystem that exists normally in the cervix and vagina and learning more about natural defenses against infection
• Finding better ways to quickly test large numbers of candidate microbicides for safety and efficacy against multiple STDs
• Creating gels or foams with optimal chemical and physical properties for carrying the microbicide 

NIAID priorities in preclinical topical microbicide research include:
• Improving techniques for rapidly screening large numbers of compounds for microbicidal activity
• Developing better small animal models for assessing safety of candidate microbicides
• Identifying compounds that act against more than one STD-causing microbe
• Developing non-human primate models of disease that more accurately mimic STDs in humans

A more detailed picture of the initial moments of infection permits researchers to begin to design, rather than merely stumble upon, possible microbicides.

In 2003, some 60 microbicide candidates were under study. These candidates can be grouped by their mechanism of action, including:
• Enhancers of vaginal acidity or natural vaginal bacteria
• Detergents that break down the outer coats of bacteria or viruses
• Inhibitors that prevent various STD-causing microbes, including HIV, from entering cells
• Substances that hinder the spread of HIV from cell to cell
(Topical Microbicides: Preventing STD; NIAID)

Basic categories of promising topical microbicides include:
- Broad spectrum microbicides
- Inhibitors of viral entry and cell fusion
- Inhibitors of HIV replication