(April 2003) As powerlessness and poverty heighten the HIV risks for millions of women worldwide, the need for a female-controlled method of HIV prevention that does not rely on the cooperation of a male partner is driving the effort to produce new products for women. To this end, the health community has intensified the search for a vaginal microbicide — a cream, gel, suppository, or other product that can protect against HIV and other sexually transmitted infections (STIs).
Current HIV prevention strategies include abstinence, monogamy, condom use, limiting partners, and treatment of other STIs. However, many women lack control over matters related to their sexuality. While the female condom offers some promise, its use is limited by cost, the need for negotiation with male partners,1 and its dual role as a contraceptive.2 These limitations underscore the need for an affordable, noncontraceptive method that women can use without male consent. Several microbicide candidates are in the pipeline, and one may be on the market by 2007.3 Researchers must, however, overcome many barriers before one of these products becomes a reality.
Microbicides Work To Prevent Infection
Microbicides are products that substantially reduce transmission of HIV and possibly other STIs when used in the vagina or rectum. They do not necessarily kill microbes, but work in a variety of ways to prevent infection.4 (See insert below, “Characteristics of the Ideal Microbicide.”)
Researchers at the London School of Hygiene and Tropical Medicine estimate that 2.5 million HIV infections could be averted in 73 low-income countries over three years if a microbicide is used under certain conditions. Such a result may occur if a product that is 60 percent effective against HIV and STIs was used by 20 percent of women in half of all sex acts that do not involve condoms.5 This would save US$2.7 billion in health care costs and US$1 billion in productivity, gained from lower levels of absenteeism and reduced retraining and replacement of workers.
Hopes of getting a microbicide to the market quickly have been dashed, however. The first candidate was nonoxynol-9, which has been used for many years as a spermicide and has some anti-HIV activity.6 Surprisingly, a study of its clinical trials showed a slightly, but not significantly, higher risk of HIV infection with nonoxynol-9 compared with placebo and a significantly higher risk of genital ulcers, caused by irritation.7 So, not only is there no basis for recommending the use of nonoxynol-9 as a microbicide, there may actually be the risk of increased harm.
Products in the Pipeline
The candidates being developed as microbicides work in a variety of ways (see Table 1). The most advanced is the Population Council’s Carraguard™, which is in phase III clinical trials.8
Microbicides in Development
|Mode of action||Products in development (organization)|
|Destroying infectious pathogens||Savvy (Global Microbicide Project/Biosyn, Inc.)|
|Providing a barrier between the infectious agent and the target cells||Carraguard™ (Population Council/U.S. Centers for Disease Control and Prevention)|
|Cellulose sulfate (Global Microbicide Project)|
|Emmelle™ (Medical Research Council/Institute of Tropical Medicine)|
|Polystyrene sulfonate (Global Microbicide Project)|
|PRO-2000 (HIV Prevention Trials Network/Biosyn, Inc.)|
|Preventing infection from taking hold||Topical PMPA (HIV Prevention Trials Network/Gilead Sciences, Inc.)|
|Enhancing vaginal defense mechanisms||Acidform™ (Global Microbicide Project)|
|Benzalkonium chloride (Biofem)|
|BufferGel™ (HIV Prevention Trials Network/ReProtect LLC)|
|Invisible Condom™ (Laval University)|
|Lectin vaginal capsule (National Institute of Allergies and Infectious Diseases)|
|Praneem (Institute of Research in Reproduction)|
|SPL 7013 (Starpharma)|
Source: Alliance for Microbicide Development, “Clinical Trials Information Center” (www.microbicide.com/Clinical.Trials.Info.Center.18Dec02.pdf, accessed April 3, 2003).
However, clinical trials of microbicides face some major obstacles, including:
- The nature of microbicides: A preventative is given to a healthy person who may then stay healthy — either because of the preventative or unrelated to it. As a result, microbicide trials, like those of vaccines, require very large numbers of participants who are followed for many months or years.
- Ethical principles: All participants must be provided with available measures known to reduce the risk of HIV infection. However, this will reduce the ability of the study to assess the protective effect of the test microbicide and increase the number of participants required to show an effect.9 Other ethical challenges relate to informed consent, confidentiality, and providing care and support to subjects who become infected with HIV during the trial.10
- Study locations: Many developing countries lack the infrastructure to conduct large clinical trials. There may be insufficient willing and able local scientific collaborators and laboratory capacity.
- Participants: Studies require sizeable populations of women at substantial risk of HIV infection — at least a 3 percent annual incidence.11 These women are likely to be already marginalized, making it difficult to recruit them to a study.
Bringing Microbicides to the Market
With funding and commitment, the earliest that an effective topical microbicide could be on the market is 2007. There are approximately 25 biotechnology companies, 38 nonprofit research organizations, five public sector entities, and 36 supportive research institutes involved in microbicide development worldwide. In March, the Bill & Melinda Gates Foundation announced the award of $US60 million to the International Partnership for Microbicides in Silver Spring, Maryland to help researchers develop a microbicide product. No major pharmaceutical firm, however, has made a significant investment in developing a microbicide product. While there are high profits to be made from birth control, the potential with microbicides is less certain. A survey by the Boston Consulting Group showed that pharmaceutical companies are interested in entering the microbicide market, but only after foundations and academic researchers develop first-generation microbicides that prove promising.12
Commercial backing will depend on the proven existence of a market for a microbicide. The most likely scenario suggests that a first-generation microbicide that meets the basic needs of women in both industrialized and developing countries could have a global market size of US$900 million by 2011. A third-generation product might have sales in excess of US$1.8 billion by 2020.13
Depending upon product specifications and cost, as many as 6 million women who are worried about getting an STI would be very interested in using a microbicide.14 Telephone interviews showed that an estimated 2.1 million U.S. women have some potential interest in using a microbicide. Some 95 percent of Brazilian women interviewed said they would be willing to pay at least US$1 per application for a dual contraceptive/microbicide product.15
Focus group discussions with taxi drivers and farmers in Zimbabwe, Mexico, and the United States showed that men are generally supportive of the idea of a microbicide. Most think microbicides would be preferable to condoms but are concerned about potential side effects.16 In another study in Zimbabwe, both men and women were concerned about how these products would work within the current gender power structure.17 These results were echoed in a South Africa study, which found that while 77 percent to 87 percent of men would like their partner to use a microbicide, most wish to be involved in the decisionmaking process.18
It would take an estimated US$775 million in direct product development expenses over the next five years to exploit the existing portfolio of microbicide leads. The small companies and academic research organizations doing almost all of the work on microbicides lack capacity for testing, formulation, manufacturing, and packaging. But coordination and international agreements could save considerable time and money. For example, companies and organizations could adopt the following approaches:
- Agreement on a standard applicator design and bulk applicator purchasing;
- Indirect cost-sharing through a co-coordinated manufacturing approach;
- Low interest loans for building manufacturing plants;
- Tax credits and incentives;
- Reducing royalty payments;
- International tendering or bulk procurement;
- Elimination of tariffs or duties; and
- Negotiated price guarantees in exchange for public investment in product development or for access to publicly financed clinical trial sites.
In many countries, approval can be heavily influenced by the decisions of the U.S. Food and Drug Administration (FDA) and the European Medicines Evaluation Agency. However, given the differences in the epidemic profile between industrialized and developing countries, these regulatory agencies may take a conservative approach to microbicides. It is important that they are involved early in the research process and that they consider the international impact of their domestic decisions.19
Effective Policies and Programs Key to Any Strategy
An estimated 1.2 million women died of AIDS in 2002, and women make up almost half of all people infected with HIV worldwide (58 percent in sub-Saharan Africa).20 A vaginal microbicide could save many lives and greatly reduce health care costs if it is introduced without users taking new risks — such as increased numbers of sexual partners or decreased condom use — because of heightened feelings of safety.21
An additional 50 million people, or double the current cumulative total, will have become infected with HIV by the end of 2007, the year researchers hope to place a viable product on the market.22 In many societies, it is the unequal economic, social, and cultural status of women that puts them at greatest risk of infection.23 Developing a female-controlled method of protection is a practical means of reducing this risk, but does not address the central issue. The most effective way to enable women to protect themselves from HIV is to tackle the gender inequalities that put them at risk in the first place. This means implementing policies and programs that increase women’s access to education; information; and productive resources such as land, income, and credit.
Heidi Brown is a health communications specialist and freelance writer on international health.
- G. Green et al., “Female Control of Sexuality: Illusion or Reality? Use of Vaginal Products in South West Uganda,” Social Science and Medicine 52, no. 4 (2001): 585-98.
- Population Council and International Family Health, The Case for Microbicides: A Global Priority, 2d ed. (New York: Population Council and International Family Health, 2001), accessed online at www.popcouncil.org/rhfp/microbicides/default.html, on March 31, 2003.
- Microbicide Initiative, Mobilization for Microbicides: The Decisive Decade (Silver Spring, MD: Alliance for Microbicide Development, 2002), accessed online at www.microbicide.org/mobilization.for.
microbicides.english.pdf, on March 31, 2003.
- Population Council, Microbicides (New York: Population Council, 2002, accessed online at www.popcouncil.org/biomed/microbicides.html, on March 31, 2003.
- Charlotte Watts et al., “New Hope for HIV Prevention: Projections of the Impact of Microbicides,” abstract presented at the Microbicides 2002 conference in Antwerp, Belgium, May 12-15, 2002.
- M. Malkovsky, A. Newell, and A. Dalgleish, “Inactivation of HIV by Nonoxynol-9,” Lancet 8586 (1988): 645.
- D. Wilkinson et al. “Nonoxynol-9 Spermicide for Prevention of Vaginally Acquired HIV and Other Sexually Transmitted Infections: Systematic Review and Meta-Analysis of Randomised Controlled Trials Including More Than 5000 Women,” Lancet Infectious Diseases 2, no. 10 (2002): 613-17.
- Population Council, “Carraguard™ — A Microbicide in Development” (New York: Population Council, 2002), accessed online at www.popcouncil.org/pdfs/carraguard.pdf, on March 31, 2003.
- Isabelle de Zoysa, Christopher Elias, and M. Bentley, “Ethical Challenges in Efficacy Trials of Vaginal Microbicides for HIV Prevention,” American Journal of Public Health 88, no. 4 (1998): 571-75.
- G. Ramjee et al., “Challenges in the Conduct of Vaginal Microbicide Effectiveness Trials in the Developing World,” AIDS 14, no. 16 (2000): 2553-57.
- Population Council, “Carraguard™ — A Microbicide in Development.”
- Arnon Mishkin, “Potential Market for Microbicides,” abstract presented at the Microbicides 2002 conference in Antwerp, Belgium, May 12-15, 2002.
- Microbicide Initiative, Mobilization for Microbicides: The Decisive Decade.
- Jaqueline E. Darroch and Jennifer J. Frost, “Women’s Interest in Vaginal Microbicides,” Family Planning Perspectives 31, no. 1 (1999): 16-23.
- Ellen Elizabeth Hardy et al., “Women’s Preferences for Vaginal Antimicrobial Contraceptives, IV. Attributes of a Formulation That Would Protect from STD/AIDS,” Contraception 58, no. 4 (1998): 251-55.
- Christiana Coggins, Kelly Blanchard, and Barbara Friedland, “Men’s Attitudes Toward a Potential Vaginal Microbicide in Zimbabwe, Mexico, and the U.S.A.,” Reproductive Health Matters 8, no. 15 (2000): 132-41.
- M. Moon et al., “Vaginal Microbicides for HIV/STI Prevention in Zimbabwe: What Key Informants Say,” Journal of Transcultural Nursing 13 no. 1 (2002): 19-23.
- G. Ramjee et al., “The Acceptability of a Vaginal Microbicide Among South African Men,” International Family Planning Perspectives 27, no. 4 (2001): 164-70.
- H. Gabelnick and M. Harper, “The Promise of Public/Private Sector Collaboration in the Development of Vaginal Microbicides,” International Journal of Gynecology and Obstetrics 67 (1999): S31-S38.
- Joint United Nations Programme on HIV/AIDS, AIDS Epidemic Update: December 2002, accessed online at www.unaids.org/worldaidsday/
2002/press/Epiupdate.html, on March 31, 2003.
- Sheena McCormack et al., “Microbicides in HIV Prevention,” British Medical Journal 322 (2001): 410-13.
- National Association of People With AIDS (NAPWA), “AIDS Is a Global Crisis” (Washington, DC: NAPWA, 2001), accessed online at www.napwa.org/pubdocs/Global%20AIDS%20CTCD.pdf, on March 31, 2003.
- Geeta Rao Gupta, “How Men’s Power Over Women Fuels the HIV Epidemic,” British Medical Journal 324 (2002): 183-84.
Characteristics of the Ideal Microbicide
- Acceptable formulation (e.g., gel, cream, foam, film, sponge, or tablet);
- Safe, including during pregnancy;
- Application possible from several hours to immediately before intercourse;
- Easy to apply;
- Sexual pleasure enhanced or undiminished;
- Stable in warm climates;
- Usable in the vagina and/or rectum;
- Compatible with barrier methods such as condoms;
- Protection against many STIs;
- Available over the counter;
- Undetectable — similar in look, smell, taste, and texture to normal vaginal secretions; and
- Available in contraceptive and noncontraceptive formulations.