March 2000
A microbicide (mi-CRO-bi-cide) is a synthetic or natural substance in the form of a gel, cream, suppository, or film that can kill or neutralize viruses and bacteria. When applied directly in the vagina or rectum before sexual intercourse, a microbicide would neutralize HIV or microbes that cause other sexually transmitted diseases (STDs) and facilitate HIV infection. Unlike other barrier methods, a microbicide could be used without the cooperation or even the knowledge of one's sexual partner. A safe, effective, and affordable microbicide could save many millions of lives. Scientists agree that such a product is within reach, yet neither private industry nor government-funded researchers are devoting adequate resources to this promising approach to prevention. To help address this need, the American Foundation for AIDS Research (amfAR) has launched a new targeted grants initiative to speed the development of microbicides that could play a critical role in reducing HIV transmission rates worldwide.
In recent years, the number of women infected with HIV has increased dramatically. Worldwide, women accounted for 44% of all people living with HIV/AIDS in 1999, as compared to 25% in 1992. In sub-Saharan Africa, the epicenter of the global epidemic, fully 55% of adults living with HIV/AIDS are women. In the U.S., women accounted for only 7% of AIDS cases in 1985. Today,one-third of all new infections in the U.S.occur among women, and this number is growing.
The best current treatment for HIV/AIDS is highly active antiretroviral therapy (HAART), a complex regimen of potent anti-HIV drugs that has been available to some HIV-positive people in the developed world since the end of 1995. HAART can prolong life by reducing the amount of HIV in the body, thus delaying the onset of AIDS.But it is not a cure. And it is much too expensive to be used in the developing countries that account for over 90% of all AIDS cases.
Preventing the sexual transmission of HIV is essential to slowing the AIDS epidemic. Worldwide, fully 90% of all instances of HIV transmission involve sexual intercourse -- 85% through heterosexual contact and 5% among men who have sex with men. In the U.S., sexual contact accounts for 53% of all new infections. Current efforts to reduce sexual transmission rates focus on minimizing high-risk behavior. However this approach does not adequately take into account the social contexts in which sexual intercourse occurs. In fact, an analysis of 27 published studies incorporating some 20,000 participants recently established that HIV counseling and testing alone was not an effective primary prevention strategy for uninfected people.
Currently, the male condom remains the only widely available barrier against sexual transmission of HIV. When used properly and systematically, condoms can achieve prevention rates close to 99%. But evidence suggests that even intensive education and distribution efforts fail to promote consistent condom use. Obstacles include a low sense of risk for HIV/STDs, the condom's impact on sensation, its contraceptive effect, religious teachings and cultural attitudes, and concerns about raising suspicions of promiscuity or infidelity. Most important, condom use requires the active cooperation of the insertive male partner. Female condoms offer one alternative, but they are costly, awkward, and still not widely available. Also, like male condoms, they usually cannot be used without the male partner's knowledge and consent. Far too many individuals do not have the power either to avoid sex with partners who may be HIV-infected or to ensure the use of condoms.
This biological vulnerability is compounded by a host of factors that put women at special risk and undermine their ability to define sexual practices and boundaries. Poverty, inequality, lack of educational and economic opportunities, social and cultural biases, and practices such as female genital mutilation exacerbate women's inability to control their sexual interactions with men. Rape is shockingly prevalent in many parts of the world; married women often risk violence and abandonment if they are not sexually compliant; and large numbers of women with few resources or skills are forced to support themselves and their children by becoming commercial sex-workers. A 19-country study conducted by the International Center for Research on Women found that the lower women's social status, the higher their rate of HIV infection. Even women who are monogamous are at risk if their partners are promiscuous. In many regions, a significant percentage of HIV-positive women were infected by their husbands.
Of course, HIV infection among women also impacts others. Each day 1,800 infants are born with HIV in the developing world, and UNAIDS estimates that there will be 13 million children orphaned by AIDS by 2001. Just as oral contraceptives dramatically enhanced the ability of women to avoid unwanted pregnancy, effective female-controlled prevention strategies are urgently needed to enable women worldwide to avoid HIV infection and other STDs.
Many experts believe that a successful microbicide will ultimately combine two or more of these approaches and require several active ingredients. There are currently 60 microbicidal products in development, many by nonprofit agencies, and 23 products have begun clinical testing. But the development pipeline is clogged. The best-studied compound, N-9, has not fared well in efficacy trials, and none of the major pharmaceutical companies is supporting microbicide research. Similarly the government's investment in microbicides is minuscule; only 1% of the federal AIDS research budget goes toward microbicides. Why?
First, there are a number of fundamental scientific questions that remain unresolved. Precisely how is HIV transmitted during sexual intercourse? Are free virus particles or virus-infected cells the major source of infectious HIV? A better understanding of sexual transmission will allow scientists to target microbicide research more effectively and develop better in vitro and animal models for microbicide testing.
The design and conduct of clinical trials in humans to test the safety and efficacy of microbicide candidates also present significant hurdles, such as choosing appropriate study populations, building local research capacity, and resolving ethical issues regarding the validity of informed consent given by underprivileged and poorly educated people at high risk of HIV infection.
Lastly, bringing a microbicide to market may require an investment of up to $500 million. Yet pharmaceutical companies do not see a viable commercial market for microbicides in the developed world. What is more, the sponsor of an effective microbicide would be under strong pressure to distribute it cheaply in the developing world. And patents on many microbicide ingredients have expired, further narrowing profit margins. Companies are also con cerned about regulatory uncertainties and the potential for unreasonable liability claims.
Answers to these and other questions will be essential to accelerating the pace of microbicide research and product development. The American Foundation for AIDS Research is committed to a broad prevention agenda, including research to design a safe, effective AIDS vaccine, prevention education,and needle exchange programs to reduce HIV infections associated with injection drug use.
With the launch of its new targeted grants initiative in microbicides research, amfAR seeks to speed the development of a new prevention technology that can be broadly utilized by anyone at risk of acquiring HIV infection through sexual contact. Given the special vulnerability of women to HIV infection through vaginal intercourse and the increasing incidence of heterosexual HIV transmission, the need for microbicides is especially urgent. These biomedical prevention agents have the potential to save many millions of lives that will otherwise be lost to AIDS, and amfAR is determined to make the promise of safe, effective, and affordable microbicides a reality for men and women worldwide.