Will Microbicides Offer an Alternative to the Condom?
What would you say if I told you that you could protect yourself from becoming infected with HIV during sex, keep from infecting someone else if you're already positive, and meet your birth control need . . . all without using a condom?
What if I said you could buy a product over the counter in any drugstore -- a gel, a cream, or a suppository -- that you could insert vaginally or rectally to get this kind of protection?
What if it was cheap, easy to use, and something your partner wouldn't even know you were using -- a "stealth" method, if you will?
Sounds good, doesn't it? Sounds like something a lot of people would run out and get if it were available. It's not . . . yet. But almost sixty possible product leads have been developed so far and are in the research pipeline. The race is on to find products exactly like this. They're called microbicides.
What's a Microbicide?As the name implies, a microbicide is something that kills microbes. For our purposes, a microbicide is any substance that substantially reduces the transmission of sexually transmitted infections, including HIV, when applied to the vagina or rectum. Like over-the-counter birth control products, microbicides can be produced in many forms, such as suppositories, films, and gels or creams that are inserted with an applicator. Sponges or rings that are inserted into the vagina and release a microbicidal product slowly over time are also being developed.
Although rectal microbicides are also urgently needed for use -- by both men and women -- during anal sex, virtually all the microbicide research now under way focuses on vaginal use. It's going to take additional grassroots advocacy and activist demand to jump-start and promote research into the simultaneous development of effective rectal microbicides. Right now, a virtual silence about them prevails.
Why A Microbicide?Microbicides are, for the most part, an unfamiliar and overlooked topic on the HIV/AIDS treatment advocacy agenda. Some people say that this is because the concept is just too new. For almost two decades now, the standard AIDS prevention message has been condoms, monogamy, and abstinence. The Condom Code has been hammered home so hard that the very idea of using anything other than a condom for HIV prevention during sex seems almost unthinkable.
The number of new sexually transmitted HIV infections, however, makes it painfully clear that the condoms/monogamy/abstinence strategy just isn't working for everyone -- no matter how much we believe that it should. Not everyone can, or will, insist on a condom every time. Other prevention tools are needed.
Some people think that the idea of microbicides hasn't caught on because the name is too weird. That's fair. It does conjure up images of pesticides or other nasty-sounding products in some people's heads. So let's come up with another, more user-friendly name! How about SuperLube, as New Woman suggested in its September 1999 issue? How about SexyGel? How about you think of a truly catchy name and send it to me care of Body Positive (19 Fulton Street, New York, NY 10038; firstname.lastname@example.org). I'm serious. All suggestions gratefully appreciated.
For whatever reason, the idea of non-condom HIV-prevention tools and the legitimacy of demanding expedited development of such options simply hasn't made it onto the HIV/AIDS treatment advocacy agenda in a big way yet. It's time to change all that.
The statistics, especially the number of women becoming HIV infected, make it brutally apparent that new prevention strategies are needed. According to UNAIDS, the Joint United Nations Programme on AIDS, more women than men are now becoming infected with HIV annually. Every day, 6,300 women around the world contract HIV. Hundreds of thousands more are infected every day with other sexually transmitted diseases. In developing countries, STDs excluding HIV are the second leading cause of illness, disability, and death among women in their reproductive years.
Women are also an ever-increasing proportion of the newly HIV-infected population of the United States. The federal government estimates that by the year 2010 at least half of all Americans infected with HIV will be women. In some parts of the country, we're already there. Young women took over the lead in Florida in 1997, when for the first time over half of all 13- to 24-year-olds diagnosed with AIDS were female. And with regard to new HIV infections among Floridians in that age group, women outnumbered men by two to one.
Unprotected sex with an HIV-positive man is by far the leading cause of HIV infection among women. Ultimately, a woman's ability to use a condom during heterosexual sex depends on the cooperation of her male partner or on her being confident and assertive enough to refuse unprotected sex. Even the internal, so-called "female" condom is visible when in place and is thus not a method that most women can use without their partners' knowledge. And like it or not, we need to recognize that some men -- for whatever cultural or other reasons -- refuse to use condoms. Without non-condom alternatives, the ongoing, rapid escalation of HIV and other STDs among women is inevitable.
But it's important that we not portray this as solely a women's issue. Men are also directly affected in two ways. The first is that "bareback" sex never went away entirely and is, according to some sources, on the rise in some parts of the gay male community. Microbicides constitute a much-needed option in the heated debate over barebacking -- a way of enabling men who engage in anal intercourse without a condom to reduce their risk of HIV infection and/or transmission substantially. This possibility alone should cause the demand for effective rectal microbicides to zoom to the top of most HIV/AIDS activist agendas.
The second way this issue affects men is that microbicides have the potential to be bidirectional. That is, using a vaginal microbicide may inactivate HIV in the vaginal secretions of an HIV-positive woman as well as in her male partner's semen. This would make them a valuable tool for individuals -- women and men -- concerned about contracting the virus, and for those of either sex who are living with HIV and who want to protect both themselves and their partners.
It is important to note that, on a per-intercourse basis, a microbicide will never be fully as effective at preventing transmission of the virus as a physical barrier such as the internal ("female") or external ("male") condom. Obviously, it is always safer to keep a virus or bacterium from getting into the body in the first place than it is to try to disable it once it's there.
Overall effectiveness, however, is determined not only by the method's theoretical efficacy but, in addition, by how consistently it is used. For those for whom consistent condom use (for whatever reason) is not an option, an effective microbicide offers a much safer alternative to unprotected sex. No matter how high its efficacy rating, a condom that is left in a drawer will not prevent the spread of HIV. Thus, in the final analysis, microbicides may be more effective than condoms in reducing HIV seroconversion rates in some populations, for the simple reason that they may be used more consistently.
Some other potential advantages of microbicides:
How Would a Microbicide Work?A wide range of product leads are being pursued with a wide range of mechanisms of action. To visualize the possibilities, think of them in five general categories:
Broad-spectrum microbicides: formulations designed to kill or immobilize pathogens.
The fact that these product leads are being pursued, however, doesn't mean that they are going to be in your corner drugstore anytime soon. Before being okayed for sale by the Food and Drug Administration, any new drug has to undergo a series of rigorous trials aimed at ensuring its safety and effectiveness. Here's how it works:
In a Phase I clinical trial, a small number of volunteers -- usually between ten and fifty -- use the product for a short period of time just to see how their bodies react to it. In this phase, researchers aren't trying to find out whether the product works -- only whether it is safe for people to use.
If the Phase I trial shows that the product is safe, a slightly larger Phase II trial is done. In this phase, with about fifty to 200 volunteers, the purpose is to gather preliminary data about whether the product actually works and to learn more about how people react to it.
If the Phase II trial is successful, it is followed by a really large Phase III trial, usually involving 1,000 to 3,000 volunteers, to test how well the product works and to find out as much as possible about it. Trial data are then presented when the company applies to the FDA for permission to market the product.
This is an enormously expensive process. According to the Alliance for Microbicide Development, it costs approximately $20 million to move one product from discovery through the completion of a Phase II trial, including preclinical lab trials and animal trials. It then takes another $20 to $30 million to move it through Phase III, because these large-scale, final tests of the product's safety and effectiveness can take one to three years to complete. For all of the potential leads now in the pipeline, the cost of doing these trials is a major problem. More about this later.
Here are some examples of products, using the various approaches described above, that are currently in the research pipeline, and where they are on the road to FDA approval:
The product has the potential to serve as a broad-spectrum vaginal microbicide because, in vitro, it has been shown to kill not only HIV but also chlamydia, gonorrhea, and syphilis. Its effectiveness in humans, however, is still unknown. Phase I safety trials have been completed successfully (with no significant problems detected) and the product is now proceeding into Phase II.
One of these is PRO 2000/5, a gel developed by a small biotech firm in the Boston area called ProCept. PRO 2000/5 has been shown in the lab to be able to keep HIV from binding itself to human cells. It may also have some effectiveness against Herpes Simplex Virus (HSV) and chlamydia, but probably isn't active against most bacterial STDs. Like BufferGel, PRO 2000/5 has also been through a Phase I trial among sexually abstinent women and is now being tested by sexually active women in the U.S. and South Africa.
Another potential lead using this mechanism of action is the Invisible Condom, created at Laval University in Quebec. This product is a thermo-reversible gel, a liquid designed to thicken after insertion. As it comes up to body temperature, it forms a physical barrier between the vaginal or rectal walls and the pathogen. After a few hours, the gel reliquifies and is discharged from the body. In lab studies, the product appears capable of blocking both HIV and HSV. Human trials of it have not yet begun.
PMPA gel, created by Gilead Sciences in the San Francisco Bay area, is a nucleoside reverse transcriptase inhibitor that is already in experimental use by people with HIV in its intravenous and oral forms. The vaginal gel form, created to see if PMPA may also be useful as a microbicide, appears in the lab to be highly effective against HIV and has shown mixed results against HSV. Phase I trials of PMPA gel as a vaginal microbicide are now pending.
Dr. Sharon Hillier, a researcher at University of Pittsburgh, has developed suppositories containing Lactobacillus crispatus, or what she refers to as the "Xena, Warrior Princess" defenders of vaginal health. By inserting these suppositories monthly, women can make sure they have large, thriving vaginal Lactobacillus colonies, and thus substantially reduce their risk of bacterial vaginosis, a vaginal condition directly linked to enhanced HIV risk.
Phase I/II trials are currently underway to determine the effectiveness of the Lactobacillus suppository in preventing a range of vaginal infections, including chlamydia, gonorrhea, and trichomoniasis. A large-scale trial is being planned to examine its utility in reducing the rate of HIV infection among high-risk women.
Research is also under way to see if "plantibodies," human antibodies produced by genetically engineered plants, can play a role in microbicide development. Scientists have successfully isolated the antibodies needed to block HIV and HSV and demonstrated that these can be mass produced inexpensively using bioengineered plants. Human trials to see if topical application of these products will actually reduce risk of infection are the next step.
Carageenan, an ordinary, inexpensive seaweed derivative already used as an additive to thicken ice cream and in some cosmetics, also holds "combination" possibilities; it turns out to have both antimicrobial properties and the ability to inhibit viral entry. In vitro, it blocks HIV, HSV, chlamydia, and gonorrhea. It has passed Phase I trials with flying colors and is now entering Phase II trials in South Africa and Thailand.
Why Not a Microbicide?The above is just a flying overview of the rapidly expanding field of microbicide development. Altogether, at the end of 1999, 38 biopharmaceutical companies, 27 not-for-profit entities, and six public-sector entities were engaged in microbicide research and development.
Given the staggering range of benefits that microbicides could have and the urgent need for them, we would expect to see microbicide research near the top of the national and international HIV research agenda, with substantial resources being devoted to getting new microbicidal products through the research and development process and onto the market as quickly as possible. Unfortunately, this is not the case.
So what's the problem?
Mostly, it's money. As described above, shepherding a product through clinical trials to FDA approval and into the marketplace costs in the neighborhood of $40 or $50 million. Small groups of researchers simply don't have the kind of cash that allows them to invest up to $50 million on clinical trials before, and with no guarantee that, they will ever be able to market their product. The big pharmaceutical companies do have the bucks, but they have yet to express serious interest in microbicide research.
At the time of this writing, the United States government's investment in microbicide research stands at approximately $23 million per year. This represents one percent of the National Institutes of Health total AIDS research budget and ten times less than is being invested federally in AIDS vaccine research, which, according to the AIDS Vaccine Advocacy Coalition, totals $223.9 million.
If public funds were supplemented by substantial private-sector investment, this extraordinarily low government allocation might not be a big problem. Unfortunately, as indicated above, the multinational pharmaceutical corporations are not yet investing in microbicide research. Their lack of interest is attributed to several factors, including perceived low profitability, liability concerns, lack of in-house expertise in this type of research (since their staff is more oriented toward HIV/AIDS treatment than prevention), and an uncertain regulatory environment.
Of these, the industry's perception that microbicides might not be profitable is the most puzzling, given that both national and international market research reveals a huge potential market. A 1999 study found that as many as 21.5 million women in the United States would be interested in using a microbicide if such a product were available. A 1998 study done by the European Union in eleven developed and developing countries showed that, even in resource-poor countries, women would be willing to pay several times more than the price of a condom for a vaginal microbicide if it were available.
Even in an informal readers' poll conducted by New Woman magazine in September 1999, 88 percent of the more than 5,500 respondents said they would be "thrilled to give the new microbicides a try." One respondent went so far as to speculate that, if proven safe and effective, microbicides could be "the most lucrative new product since the WonderBra."
A powerful, albeit largely unexpressed, public demand for these products can be documented. Despite this, the only serious money going toward getting these products onto the drugstore shelves is the very limited amount allocated by the U.S. government. This alone just isn't enough to do the job within a reasonable time.
A blockage is developing in the research pipeline as a result of inadequate research funding, and it's only going to get worse unless substantial new resources become available.
Of the 56 promising product leads identified by late 1999, 33 were still at the preclinical research stage (i.e., being studied in labs but not in humans), sixteen were in Phase I safety trials, four were in Phase II safety and effectiveness trials, and three were in Phase III -- the final trials that are done to see if a product is safe and effective enough to go to the FDA for consideration and possible market approval. The number of products in the pipeline has doubled since 1994, when fewer than thirty had been identified.
As stated earlier, it takes about $20 million to get a product from discovery through the Phase II clinical trials and another $20 to $30 million just to get it through Phase III, because these final trials are necessarily massive to ensure the product's safety and efficacy before it is released onto the market. The result is that the lack of funds translates into a blocked research pipeline.
The bottom line, obviously, is that sufficient money hasn't been allocated to move even one of the promising products now in Phase II trials through that final Phase III step. As more products advance through Phase II in the coming years, the logjam will only get worse unless additional investment in microbicide research is forthcoming.
In the last decade, an historic level of highly vocal demand and public activism got HIV/AIDS combination therapy -- HAART -- drugs through the research and development pipeline and the FDA approval process and into the hands of people living with HIV/AIDS with unprecedented speed. So we know it can be done.
The great African-American abolitionist Frederick Douglass wrote that "power accedes nothing without a demand. It never did and it never will." How soon we get microbicides into the hands of all of us who need them depends primarily on how soon we start demanding them loudly.
How much longer are we willing to tolerate the absence of alternatives to condoms?
How many more lives will be lost before the activist community -- all of us who care about stopping the spread of deadly, sexually transmitted infections among women, men, and their children -- join in raising a loud public demand for meaningful microbicide funding?
For two decades now, we have confronted the raging pandemic of AIDS by handing people condoms. To borrow from ACT UP, "How many more have to die before you join the fight?"
Anna Forbes is an AIDS and women's health policy consultant based in Ardmore, Pennsylvania. This is her first contribution to Body Positive.
This article was provided by Body Positive. It is a part of the publication Body Positive.