Get ready: Women to have more options for preventing disease
Partnership is key to getting products into market
(Editor’s note: This is the second of a two-part series. In last month’s issue, Contraceptive Technology Update presented an overview of vaginal microbicides. This month, CTU discusses the efforts to provide female-controlled protection and focuses on products being researched.)
Expanding the options for preventing HIV and other sexually transmitted diseases (STDs) is more urgent than ever due to the increase in heterosexual HIV transmission. Women now account for 19% of all adult AIDS patients in the United States.1 The rise of STDs, termed "the hidden epidemic" by leading U.S. health experts, represents a deep concern for women because complications of STDs are greater and more frequent among women than men.2
Vaginal microbicides offer women a self-controlled method of protection that does not require partner knowledge or cooperation. Microbi cides may or may not have spermicidal properties. A microbicide that is not also a spermicide may prevent disease but not pregnancy.3
While there are several promising leads in the research and development pipeline, no one product has yet made it to the market shelves. Several companies, scientists, and advocates have banded together to form a consortium, the Alliance for Microbicide Development, based in Takoma Park, MD. The group is focused on improving the efficiency of pre-clinical devel opment processes, tracking product progress through research and development, providing information to the public and policy groups, and fostering the building of a funding base to support combination and comparative studies.
Some 27 biopharmaceutical companies, 10 research entities, eight advocacy groups, and several consultants have joined the alliance, reports its director, Polly Harrison, PhD. "We want to get the pipeline unblocked," she says. "There is a serious need for these products."
The term "microbicides" serves as an umbrella for a wide variety of products. By definition, mic ro bicides are substances that destroy or incapacitate infection-causing organisms, including bac - teria, viruses, and parasites. Some preparations are combining spermicides such as nonoxynol-9 (N-9) or octoxynol-9 in carriers such as a gel, foam, cream, film, or suppository. Others represent novel approaches such as an acid-buffering gel or viral inhibitors.
Researchers are examining use of these products as both a spermicide and microbicide, offering dual prevention against both pregnancy and disease. Investigation also is focusing on use of these products as stand-alone microbicides for women who need disease protection but desire to have children, or for men who have sex with men.
Following is an overview of some of the products in the pipeline, with a focus on those that may offer prevention against both pregnancy and HIV/STD:
BufferGel is a polymeric gel developed by three Baltimore-based Johns Hopkins University researchers who formed ReProtect LLC to bring the product to market. An extensive Phase I safety trial has been successfully completed in Provi dence, RI, reports Richard Cone, PhD, professor of biophysics at Johns Hopkins and managing director of ReProtect. The trial was sponsored and performed by HIVNET, the HIV Network for Pre ven tion Trials coordinated through the National Institutes of Health in Bethesda, MD.
HIVNET is now pursuing additional Phase I tests of BufferGel at four international sites, says Cone. If the product is found safe for women to use at these international sites, HIVNET will decide whether to pursue Phase II tests of Buffer Gel for preventing common STDs. If BufferGel is shown to be effective in Phase II trial, HIVNET might proceed to the much larger trials needed to test whether BufferGel is effective against HIV infections.
BufferGel is formulated at pH 4, the same mild acidity as the healthy vagina, explains Cone. It has sufficient buffer capacity to acidify semen, thus helping to maintain the protective acidity of the vagina. Mild acidity rapidly kills sperm, syphilis, and white blood cells, which may be motile vectors for transmitting HIV and other STDs, says Cone. The same acidity more slowly kills STD pathogens, including HIV, herpes simplex virus, chlamydia, and gonorrhea.
BufferGel is being evaluated as a stand-alone product, as well as serving as a pre-coating to a disposable barrier device, such as a diaphragm or cervical cap, for further protection enhancement.
BioSyn, a Philadelphia-based company, is working with its C31G technology in looking at HIV, STD, and pregnancy prevention. The company’s technology rests on a family of molecules that attaches to the surface of bacteria, yeast, and enveloped viruses such as HIV and rapidly inactivates them, says Daniel Malamud, PhD, professor of biochemistry at the University of Pennsyl - vania and BioSyn’s vice president of research and development.
The C31G technology is in two Phase I human clinical tests: one a safety and efficacy trial, and the other an irritation study to ensure there are no untoward effects on mucosal tissues, Malamud says. Because the C31G material is active against a variety of pathogens, BioSyn plans to evaluate it against a series of STDs, including HIV, says Malamud.
PRO 2000 Gel is a synthetic colorless, odorless polymer with high thermal stability developed by Procept, based in Cambridge, MA. Company vice president Al Profy, PhD, says PRO 2000 coats HIV and prevents it from infecting susceptible cells. It also seems to coat the head of the sperm and prevent fusion with the egg, he notes.
Pre-clinical in vitro studies have shown that PRO 2000 can block infection by HIV, herpes simplex virus type 2 (HSV-2), and chlamydia. During in vivo studies, PRO 2000 Gel was shown to provide complete protection against vaginal HSV-2 infection in mice.
Two Phase I clinical trials were conducted at the Institute of Tropical Medicine in Antwerp, Belgium, and at St. Mary’s Hospital in London, with funding from the British Medical Research Council. Those trials showed that daily use of PRO 2000 Gel was safe and well-tolerated, Profy says, and participants found the product aesthetically acceptable. A study funded by the National Institutes of Health to assess all potential uses of the product, including STD prevention and contraception, is slated to begin this year, he says.
The Infectious Diseases Research Center at Canada’s Laval University in Sainte Foy, Quebec, has developed a nontoxic polymer-based liquid that solidifies into a gel when applied to the body. Dubbed the "invisible condom," the gel, which forms a waterproof film, reduced transmission of HIV and the HSV-2 in laboratory and animal tests.
Plans are to study the material for protection against STDs and pregnancy, says Michel Bergeron, MD, FRCP, director of the Laval University’s division of microbiology and the Infectious Diseases Research Center. Clinical research should begin in the fall, with approval sought in worldwide markets. The center is negotiating with major companies to bring the product to market, Bergeron says.
The Hughes Institute in Roseville, MN, has received funding from the National Institutes of Health to develop two novel compounds in products that will provide HIV and pregnancy prevention. The two compounds, aryl phosphate derivatives of bromo-methoxy-azidothymidine, show powerful spermicidal and microbicidal effects when tested in hamsters and mice.4 Researchers say the compounds may be useful as dual-function vaginal contraceptives for women who are at high risk for contracting HIV. (Research is examining the use of spermicides such as nonoxynol-9 in new carrier agents. Read more about these products on p. 40.)
1. Wortley PM, Fleming PL. AIDS in women in the United States. JAMA 1997; 278:911-916.
2. Wasserheit JN, Holmes KK. Reproductive tract infections: challenges for international health policy, programs, and research. In: Germain A, Holmes KK, Piot P, Wasserheit JN, eds. Reproductive Tract Infections: Global Impact and Priorities in Women’s Health. New York: Plenum Press; 1992.
3. Barnett B. Microbicide research aims to prevent STDs. Network 1996; 16:15.
4. D’Cruz OJ, Venkatachalam TK, Zhu Z, et al. Aryl phosphate derivatives of bromo-methoxy-azidothymidine are dual-function spermicides with potent anti-human immunodeficiency virus. Biol Reprod 1998 September; 59:503-515.
For more information on the Alliance for Microbicide Development, contact:
• Polly Harrison, PhD, Director, or Gretchen Kidder, Research Associate, Alliance for Microbicide Develop ment, 6930 Carroll Ave., Suite 830, Takoma Park, MD 20912. Telephone: (301) 270-5924 or 5925. Fax: (301) 270-5926. E-mail: firstname.lastname@example.org or email@example.com.