Johns Hopkins Bloomberg School of Public Health: The INFO Project

Microbicides could help women protect themselves against STIs when they cannot use condoms. Women could control use of microbicides, perhaps without needing the cooperation of their partners.

Some women lack the power to ensure consistent and correct condom use. Relationships that subject women to coercion, violence, and dependency can make it difficult or impossible for them to negotiate condom use or to leave the relationship even though it puts their health at risk (10, 50, 54). While microbicides will not level these power imbalances, they could give women another option to reduce their vulnerability to STIs, including HIV/AIDS (99, 125).

Women pose outside a teaching hospital in Soweto, South Africa. Researchers at the hospital are assessing the prevalence of HIV and whether a microbicides clinical trial in Soweto would be feasible.

Some women may not be able to use a microbicide without detection by their partners. Consequently, some women facing risk of violence from their partners may not be able to use a microbicide (67). For those not at risk of violence, however, discussing microbicide use with their partners could help increase intimacy and shared responsibility for HIV protection (68).

Women who lack the power to ensure the use of condoms are at far greater risk than men because women are biologically more vulnerable to HIV and its consequences. The rate of transmission of HIV from men to women is at least two to eight times greater than the rate of transmission from women to men because during sex the vaginal epithelium is easily torn and there is more HIV in semen than in vaginal secretions (24, 84, 87). Adolescent women are at greatest risk because the cervix is physiologically less mature and therefore more vulnerable to infection (104).

Some of the microbicides currently under development would provide women a method to protect themselves not only against HIV/AIDS and other STIs but also against pregnancy—that is, they would provide dual protection. Conversely, some microbicides may allow women to become pregnant while reducing the risk of HIV or other STI transmission, which is not possible with condoms, which protect against both STIs and pregnancy when used consistently and correctly. In cultures where a woman’s status and self-esteem depend primarily on her fertility, many women will want the ability to become pregnant but at the same time to reduce their risk of HIV/AIDS (85).

Several organizations advocating microbicides have estimated the costs of microbicide development, based on average costs of phase I, II, and III clinical trials and average registration costs—that is, the costs involved in obtaining regulatory approval in a country. The Rockefeller Foundation’s Microbicide Initiative in 2002 estimated that developing a single microbicide from preclinical research to registration would cost an average of $US57 million (89). Another estimate from the same study was that about US$775 million in direct product development costs would be required over five years to complete clinical trials for all of the microbicides then in the development pipeline.

A more recent estimate by the Alliance for Microbicide Development, based on new expenditure data from developers, estimated the cost for developing a microbicide candidate at approximately US$35 million. The total cost of moving the most advanced products through the final stages of research and to market was estimated to be US$966 million or more for the 12-year period 2004–2016 (63).

The costs could prove to be substantially lower or higher than these estimates. The development costs of each microbicide product differ widely and depend on many factors—for example, whether the compound is new or has been used previously, and whether it requires long-term studies of toxicity or carcinogenicity (30). For these reasons new estimates will be made in 2005, based on an extensive review of the costs of all products in development (42).

One estimate puts government funding and private grants for microbicide development for the four-year period 2001 to 2005 at about US$230 million worldwide (89). The Alliance for Microbicide Development estimates government funding and private grants for 2001–2004 to be substantially higher, at US$487 million (42). Still, these estimates are much lower than the funds needed to develop a microbicide candidate.

Microbicide Clinical Trial Sites Microbicide clinical trials are underway in 19 countries—15 developing and 4 developed.

Current clinical trials in 19 countries (15 developing and 4 developed) are supported almost exclusively by small biotechnology companies, academic centers, nonprofit and government organizations, and private foundations (43). (See “Key Organizations Supporting Microbicide Development”)

Advances in microbicide development have come almost exclusively through public-sector investment (53, 94). The US and British governments (47, 116) and the European Commission (55) have contributed substantially. Such private US organizations as the Rockefeller Foundation, the American Foundation for AIDS Research (amfAR), and the Hewlett Foundation also have funded microbicide development and clinical trials in recent years. The Bill and Melinda Gates Foundation alone has provided US$124 million as of 2004 (107).

No major pharmaceutical company has made a substantial contribution to microbicide development (43, 128). Major pharmaceutical companies have been reluctant to invest heavily in microbicide research and development because of liability concerns, regulatory hurdles, high costs, disinterest in nonprescription products, and an uncertain market for microbicides (48, 56, 89). These companies are likely to become interested in microbicide research, however, if a first-generation microbicide produces a high level of demand (81).

Initially, as the developers introduce the first generation of microbicides, the expected potential world market for them is estimated at about US$1 billion per year. Over the long term, as microbicide formulations improve, this figure could grow to between US$1.8 billion and US$2.6 billion per year (89).

Bringing an effective microbicide to market soon will require close collaboration among public and private research institutions and the major pharmaceutical companies (31, 56). Governments can further encourage private firms to develop microbicides by lowering the costs and risks of research and development. For example, governments can offer tax credits, make it easier for researchers to conduct clinical trials, and conduct regulatory reviews faster to support companies that conduct microbicide research and development (1).