Friday, January 19, 2007

Considerations for Real-World Use of Microbicides

For more than ten years, the scientific community has been touting microbicides as the next big breakthrough in HIV/AIDS prevention. Microbicides are compounds that protect against sexually transmitted infections such as HIV and can be applied inside the vagina or rectum as a gel, cream, film, or suppository. Numerous strategies for microbicides are currently in development, including disruption of HIV’s viral envelope, maintenance of the normally acidic environment of the vagina, nonspecific inhibition of viral entry or fusion by creating a film over vaginal cells, and specific entry inhibition by providing competing ligands for receptors on CD4 cells. Despite the promise of various microbicides, results from efficacy trials will not be available for several more years. There are several areas of consideration when deciding which of the numerous microbicides in development will be realistic for real-world applications.
The first important factor to consider is the microbicide’s safety. Recent studies of nonoxynol-9 showed that the hopeful microbicide actually increased the risk of HIV infection. In vitro, N-9 disrupted the HIV envelope and prevented fusion. In vivo with prolonged use, however, the drug disrupted the vaginal epithelium, resulting in inflammation and a gathering of the immune cells. This aided HIV in overcoming the body’s natural defenses. This example shows that possible interactions with the body must be considered. Other safety issues should include complications from other sexually transmitted infections, drug resistance development in unknowingly infected women, and carcinogenicity of a compound continually applied to the vagina or rectum.
The next important real-world consideration is the acceptability of the microbicide. Many women will refuse to use something if it inhibits fertility. Thus, an effective microbicide should not also be a spermicide. In addition, the microbicide should be able to be applied well in advance of sex, in order to aid in secrecy of use if necessary. The microbicide should not be difficult to use or have an unusual consistency or smell. Finally, some countries in the world may not like microbicides based on genetically modified microorganisms.
One of the most important concerns is the efficacy of the microbicide. At the 2006 Microbicide Conference in South Africa, scientists began to push for drugs with higher potency towards HIV instead of drugs that are less effective but might prevent multiple sexually transmitted infections. In order to be truly effective, the microbicide would combine multiple methods of HIV prevention. A 2006 study by Robert Neurath found that some microbicides are extremely effective in vitro. However, development of these drugs did not take into account the nature of seminal plasma, a compound certain to be present in heterosexual intercourse. Neurath found that the plasma changed the pH environment significantly enough to alter the efficacy of the drug. This demonstrates just one of many possible interactions unaccounted for in current research and development.
The final factor in real-world use of microbicides is affordability. It is estimated that for microbicides to be available to donate to developing countries, each application must cost less than a dollar. Currently, only large pharmaceutical companies can afford the high cost of development of microbicides, which can cost up to tens of millions of dollars. Companies have little financial reason to develop these drugs when they are aimed primarily at poor women in developing countries. However, in 2003, the Bill and Melinda Gates Foundation pledged $60 million to aid with microbicide research aimed at HIV/AIDS, aiding the small laboratories struggling to develop these drugs. Ultimately, the investment will pay off. The World Health Organization estimates that a microbicide which only reduced the risk of infection by 40% and was only used in 30% of women in low-income countries would prevent approximately 6 million HIV infections in 3 years. This would reduce health care costs, not including the cost of antiretroviral drugs, by 3.2 billion US dollars.
More than 60 different microbicides are in development or testing currently. Not all of these, however, will meet the important criteria for real-world use. Even for those that do, data will not be available for several more years. The time and cost of development, however, is far outweighed by the hope that such a drug would give to the at-risk female population of the world.

This has been Cara Maguire.

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