What's flowing through the microbicide pipeline: approaches range from complex to simple.

The microbicide research field is varied and diverse, with the potential for products that will include vaginal and/or rectal gels, films, creams, or suppositories to oral medications, which have active ingredients that range from hormones to antiretroviral drugs, fusion inhibitors, or surfactants.

Products also vary in what they do: Some are designed solely to prevent HIV infection, while others also will work as spermicides or prevent infections by other sexually transmitted diseases (STDs).

What eventually will be developed and marketed will depend largely on the availability of funding and the industry's and international AIDS community's interests, experts say.

However, a few products have a head start in the race for a successful microbicide, including several currently scheduled for phase III clinical trials.

The first generation products are based on negatively charged polyanions, says Robin Shattock, PhD, reader in cell biology of infection, department of cellular and molecular medicine, infectious diseases at St. George's Hospital Medical School in London. "We understand a great deal about their safety, and they all clearly inhibit HIV infection in the test tube," she says. "They are cheap, easy to manufacture products that are unlikely to suffer from problems of resistance."

These first products are nonspecific in their activity, ready for phase III clinical trials, and may have a chance of showing some efficacy, Shattock adds.

Next in the pipeline are a wide range of products that may prove to be more effective microbicides, but which are a few years away from phase III clinical trials, he adds.

"Of particular promise would be the topical use of antiretroviral agents that already have a proven track record against HIV replication," Shattock says. "These products are highly likely to succeed in preventing infection, but their use may be complicated by potential resistance acquisition in the developing world."

These products are followed by a range of fusion inhibitors and coreceptor antagonists. While these products hold promise, they also have potential problems with regard to mass…