The basic idea is simple: correctly apply the microbicide – a gel, vaginal ring or cream – to the vagina, and under ideal circumstances, this method will prevent the transmission of HIV. No more worrying about men who refuse to use condoms.

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Since HIV and other sexually transmitted infections (STIs) attack the body in a number of ways, and in a number of steps, there are dfferent ways being explored to stop infection from taking place. As a result, 'microbicides' is a bit of an umbrella term, used to refer to a variety of mechanisms to prevent transmission.

Five basic mechanisms

Vaginal defence enhancers
The vagina has developed a number of natural defences against infection. One of them is a low pH (acidity). Semen, which is alkaline, temporarily neutralises this acidity so that sperm can survive in the vagina. This temporary lack of acidity also gives viruses a window of opportunity in which infection can take place.

So-called acid-buffering microbicides are designed to counteract semen’s neutralising effects and to keep the vagina acidic in order to inactivate sperm and HIV.

Physical barriers
Entry infusion inhibitors could provide a physical barrier between pathogens and vulnerable cells in the epithelium (cell wall) of the vagina. These microbicides clog things up in the vagina by attaching to HIV or target cells. The idea is that things will get so clogged up that the transmission of HIV becomes impossible.

Three products in this class are currently in effectiveness trials. One of these trials, being conducted in South Africa, has enrolled over 6 000 women, and is testing a product called Carraguard, which contains the seaweed derivative, carrageenan. Carrageenan is often used as a gum to thicken products like ice cream and marshmallows.

Inactivating pathogens
Some microbicides, called surfactants, work by poking holes in the surface or membrane of a virus – a bit like the way in which soap breaks down dirt. This compromises the virus and essentially renders it incapable of causing an infection.

Some surfactants may, however, damage more than just the virus being targeted. Thus, researchers are focusing on low concentrations of such surface-acting microbicides that are unlikely to harm the epithelium, the protective layer of cells lining the vagina and rectum.

Prohibiting viral entry
In order for HIV to infect a cell, a specific protein on the virus must bind with a specific receptor on the target cell's membrane in a rather complicated process. Some microbicides interrupt this process by introducing other molecules that will bind with the receptor before HIV has the chance to do so.

Inhibiting viral replication
Some microbicides, called replication inhibitors, build on the discoveries of anti-retroviral therapies to prevent replication even after the genetic material of a virus enters a target cell, thereby decreasing the chances that the virus will be able to multiply and infect other host cells. Researchers are focusing on microbicides that target the HIV reverse transcriptase enzyme, critical for HIV replication.

The jury is still out
Which of these mechanisms will prove most effective in stopping the transmission of HIV is still unclear. Ideally though, women would eventually be in a position to choose from a variety of microbicides to suit their specific needs.

It is, for example, quite likely that microbicides that work by manipulating pH levels in the vagina, may also act as a contraceptive. Other microbicides that target the HI-virus more directly, would probably not have a contraceptive effect.

Furthermore, microbicides will also differ in the way they are administered. Some gels being tested at present are inserted into the vagina approximately an hour before sexual intercourse, by means of a special applicator. Other microbicides may come in the form of a vaginal ring that would be used on a monthly basis.

Trials under way
There are currently 16 microbicide products undergoing clinical trials, of which five are in large case effectiveness trials. Results from some of these may be available as soon as 2008. And, according to some optimistic projections, a microbicide may be available for use by 2010.

The risk profile for microbicides will vary, but generally seems to be quite low. A product like Carraguard (mentioned above) appears to be extremely safe, while microbicides making use of anti-viral therapies may carry more significant risks, said Lori Heise, director of the Global Campaign for Microbicides.

Some early microbicide studies made use of the spermicidal nanoxynol-9 (N9), which has been used in contraceptive products for years. In some studies N9 was found to actually increase the risk of HIV transmission. Subsequent studies have not yet exposed similar risks with other products.

Science - only half the battle
But, even if an effective microbicide were available by 2010, as it would be with a best-case scenario, many challenges would remain.

"A microbicide is not going to be a magic bullet. The very same factors that combine to make microbicides a necessary intervention – gender norms, lack of economic and social power, double standards around sexuality – will be barriers to women being able to use them consistently. We have to work on both sides of the equation – giving women tools and addressing the underlying power issues that condition their risk," Heise told Health24.

Furthermore, as with nevirapine and antiretroviral therapies, the rollout of microbicides may face some severe delays. At the recent Microbicides 2006 conference in Cape Town, the South African government did, however, pledge their commitment to a fast and effective rollout, if and when effective microbicides become available.

Whatever difficulties lie ahead, the stakes are high: a recent report calculated that "a microbicide that's 60 percent effective against HIV, and used by only 20 percent of women in 73 developing countries could prevent 2.5 million HIV infections".

– (Marcus Low, Health24)

Sources:
Microbicide Watch (2006)
Global Campaign for Microbicides

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