Johns Hopkins Bloomberg School of Public Health: The INFO Project

Researchers have been pursuing the development of microbicides for almost 20 years (13). Until recently, microbicide development progressed slowly, in part because resources for research and development were scarce, including funding, expert researchers, and a research infrastructure (110, 111).

Clinical trials in particular face additional obstacles (18, 35). To reduce risk of HIV infection among participants in clinical trials, researchers encourage all participants to use condoms. This is an important precaution because some participants will receive a microbicide that has yet to be proven effective, while others will receive a placebo—containing no microbicide at all. In some clinical trials, still other participants will receive only condoms. Because some people in all groups will use condoms, HIV transmission rates will be lower than they otherwise would be. Thus more participants and a longer study period will be required to detect a difference in HIV transmission rates between groups—the objective of the studies. Researchers often find it challenging to recruit enough volunteers to provide significant results (71, 99, 110).

The funding for clinical trials is often insufficient to support the large participation necessary, and the number of feasible sites for clinical trials is limited (13, 109). Disagreements among researchers related to the design of clinical trials and protocol have contributed to delays (18, 27, 35).

A booklet from the Population Council about study procedures, risks, and benefits helps to achieve informed consent in a phase III clinical trial.

The regulatory process is lengthy. In many developing countries approval of medical products is heavily influenced by the decisions of the US FDA and European Medicines Evaluation Agency (EMEA) (18, 80). Regulatory authorities in developed countries, however, are likely to take a more conservative approach to regulatory decisions about microbicides than are those in most developing countries (18, 27).

Although both developing and developed countries require demonstration of safety and effectiveness before a medical product can be marketed, regulatory processes in developed countries may take longer than some developing countries are prepared to wait (18). The need for a microbicide is especially urgent in developing countries where HIV/AIDS is at catastrophic levels. To hasten microbicide introduction, some microbicide advocates recommend that the regulatory agencies of some developing countries, such as South Africa and India, evaluate the results of candidate microbicide clinical trials independently, rather than wait for the US FDA and EMEA to complete their review processes (95, 108).

The first generation of microbicides to reach the market will probably not be as effective as male condoms in protecting against STIs, including HIV/AIDS, when each method is used consistently and correctly (106). Male condoms are 90–95% effective in preventing HIV when used consistently and correctly (90). In contrast, the first microbicides are expected to be just 50–60% effective with consistent and correct use (110).

Many people do not use condoms, however, or use them incorrectly and inconsistently (32). In actual use, therefore, a vaginal microbicide might prevent more HIV and STI infections than condoms do in typical use, if more people use microbicides and use them correctly (28, 58, 97).

Microbicides, even though they are less effective than condoms, would prevent more infections than condoms now prevent because higher rates of use would more than make up for lower effectiveness rates. For instance, if microbicides are 50% effective, then high-risk groups using them in half of their sex acts would have about the same level of protection against HIV as people who use condoms only in one-quarter of their sex acts, even assuming that condoms are 95% effective (28).

The public health benefits of even a partially effective microbicide would be substantial. One conservative estimate based on computer modeling is that, even if only 20% of people in high-risk groups used a microbicide that was just 60% effective in protecting against HIV infection, 2.5 million lives would be saved in its first three years (97).

Widespread availability of microbicides could reduce condom use somewhat, as some people switch from condoms to microbicides for protection (58, 97). Nevertheless, computer modeling demonstrates that shifts from condom use to microbicide use would rarely be enough to result in an increase in HIV infection rates (28, 58).

Second- and third-generation microbicides are likely to be more effective than the first-generation formulas (106). They will combine several active ingredients in a formulation that works in several ways to combat infection. These advances would decrease the potential for pathogens to develop resistance to the microbicide, protect people who are HIV-positive from reinfection, and protect against more STIs. They would reduce the concentration of potentially toxic agents, reducing irritation to the vaginal epithelium and toxicity to the natural, beneficial organisms in the vagina (106).

For example, preliminary studies of PRO 2000 and a monoclonal antibody (a type of vaginal defense enhancer) have found that, when used together, they could provide better protection than the sum of the protection that each affords individually (29). Also, researchers at the Population Council are working on developing PC-815, which is a combination of Carraguard, an entry and fusion inhibitor, and MIV-150, a replication inhibitor (103).

Widespread acceptance and use of microbicides could lead to considerable savings in public health expenditures. Computer modeling projects a savings over three years of US$2.7 billion worldwide in health-system costs and an additional US$1 billion in productivity savings because of less worker absenteeism and lower employee training and replacement costs related to STIs (97).