Microbicides Against HIV

Women are increasingly at risk of contracting the HIV virus, and yet the most well-known method to prevent transmission during sexual activity is ultimately a decision made by the man.

But the days where male condoms are the best and easiest solution might be coming to an end as four different forms of microbicides - gels or creams with antivirals women can apply vaginally to prevent HIV (human immunodeficiency virus) infection - are now in final testing phases.

Experts say a total of more than 60 microbicides are in various stages of development and testing with some formulated as a pre-loaded diaphragm, cervical cap, sponge or vaginal ring releasing an active ingredient over time. The different microbicides include antivirals that use different methods of targeting the cells and virus.

"We know if there are more options, it's more likely to be used," said Anna Forbes, deputy director of the Global Campaign for Microbicides, a nonprofit organization based in Washington, D.C.

The first microbicide expected to complete testing is Carraguard, which is made from seaweed. It's being developed by the nonprofit Population Council in New York. Phase III trials are being conducted in three locations in South Africa and will be completed in March 2007.

Analysis of the data should be published by the end of 2007, and if Carraguard shows effectiveness at blocking HIV transmission, the council will seek the first regulatory approval from the South African Medicines Control Council. The council does intend to seek approval afterwards, if the data justifies it, by the U.S. Food & Drug Administration.

"Our goal is to develop a product used by women in the countries hardest hit by HIV and so we will work with regulatory entities in those countries," said Melissa May, director of public information for the council.

New Prophylactic

So far, Carraguard hasn't shown any significant side effects in testing on animals and humans, according to May.

"It's hard" for many of these women to persuade their partners to use condoms," May said. "Women really liked" the concept that they were in control with microbicides, she added. May noted that an additional benefit comes from the increased lubrication that the microbicides provide, a feature received positively both by men and women in testing.

Carraguard is currently being tested for use one hour before intercourse. But later testing and the subsequent versions of microbicides will be tested for use up to 24 hours or even on a monthly basis, according to Dr. Zeda Rosenberg, chief executive of the nonprofit International Partnership for Microbicides of Silver Spring, Md.

That would be a particular incentive for use in areas such as Darfur, where gang rapes are commonplace and a leading source for HIV transmission. Young girls could use microbicides as well, as rapes of children are on the rise. Subsequent microbicides are expected to be tested for effectiveness in blocking HIV transmission during anal sex.

The efficacy of first-generation microbicides is expected to range from 40% to 70%, with the lowest rate averting 18% of infections; and at 60% effectiveness, 35% of infections could be prevented. That could translate into countless lives being saved - more than 25 million people have died of AIDS since 1981, according to a recent report by the United Nations AIDS/World Health Organization. HIV causes AIDS (acquired immunodeficiency syndrome) by damaging white blood cells and other defenses against infection.

Currently, the only known way to spread the HIV virus is through the exchange of bodily fluids such as blood or semen from an infected person.

Cost-Effectiveness

Most versions of microbicides are coming from nonprofit organizations such as the Population Council and from small companies, such as Polydex Pharmaceuticals Ltd. (POLXF) of Canada. Pharmaceutical powerhouses such as Bristol-Myers Co. (BMY), Merck & Co. (MRK) and Johnson & Johnson (JNJ) are providing compounds for research as well.

It makes sense for the nonprofit organizations to take the leading role in the development of microbicides since they are better positioned to conduct trials in the developing world, according to John Moore, a professor of microbiology and immunology at Weill Medical College of Cornell University in New York. Moore has been working with Bristol-Myers and Merck on these projects.

Experts say that among the three compounds from the major companies, the Bristol-Myers and Merck versions stop the HIV virus from entering cells whereas the Johnson & Johnson compound - developed by its Tibotec subsidiary - stops replication of the virus.

TMC120, the Tibotec compound, is in a number of Phase I/II trials, according to Karen Manson, a spokeswoman for Tibotec, which is collaborating with the International Partnership for Microbicides.

The primary audience, at least initially, for microbicides are mostly women who live at the poverty level.

With antiviral therapy, "if it's not inexpensive," it won't be used, said Polly Harrison, director of the Alliance for Microbicide Development of Silver Spring, Md.

This could be very attractive for companies that are interested in "high-volume and low-margin products," the International Partnership for Microbicides' Rosenberg said.

The U.N. estimates that nearly 40 million people worldwide are currently living with HIV and AIDS, including 4.3 million newly infected in 2006. More than half of new infections are occurring in women. Research has shown that women are biologically more vulnerable to infections.

High-Profile Support

Meanwhile, 45 million new HIV infections are expected to occur between 2002 and 2010. Across sub-Saharan Africa, where the highest rates of infection are occurring, UNAIDS/WHO said that women between 15 and 24 years old are at least three times more likely to be HIV-positive than young men.

The dollar amounts targeted for microbicide research have grown tremendously amid public support from former President Bill Clinton, the Bill and Melinda Gates Foundation, the Rockefeller Foundation and others. Five years ago, much of the focus on HIV prevention was on finding a vaccine, but today many experts are more encouraged about the potential immediate impact of microbicides. In 1997, about $28 million was given to fund microbicide research; in 2005 that grew to $163 million.

In a Rockefeller Foundation report, estimates for the net present value of investing in a first-generation microbicide range from negative $65 million to negative $27 million. The second-generation product could be self-funding, with figures ranging from a negative $56 million to a positive $122 million.