SEARCHING FOR 'MAGIC' LUBE
What if the lubricant you use for sex could completely protect you from HIV infection? That dream of gay men and prevention advocates took a step closer toward reality with a research workshop on rectal microbicides June 7-8 in Baltimore, Md. It drew together researchers with the global HIV Prevention Trials Network.
"Twenty years into the epidemic we still know next to nothing about how HIV is transmitted during anal sex," said Ken Mayer, a researcher at Brown University who is associated with the Fenway Community Health Center in Boston. "We must gain a better understanding of that transmission in order to develop new tools of prevention intervention to supplement condoms."
Research strongly suggests that anal sex carries a greater risk of HIV transmission than does vaginal sex. Most people automatically assume that anal sex is just a gay male thing, but behavioral research shows otherwise. While heterosexuals are much less likely than gay men to engage in anal sex, there are simply so many more of them that the total amount of heterosexual anal sex likely is several-fold that of gays.
Even more troubling is the fact that straight couples appear to be much less likely to use condoms when they have anal sex then when they have vaginal sex. That is because they tend to think of condom use in terms of preventing pregnancy rather than preventing disease.
Technically, a microbicide is a chemical agent that kills a microbe, any infectious agent such as the sexually transmitted diseases ( STDs ) gonorrhea, syphilis, or HIV. But in a practical sense the word also includes protection gained through internal barrier mechanisms, compounds that inhibit the pathogen's ability to enter the body, and measures that strengthen the body's natural defenses against such invaders.
Just as combination therapy is needed to hold HIV in check, so too the best protection with microbicides likely will include several of these approaches. The compounds will be added to the lube and the only way you will be able to tell what is in it is by reading the label. That's the goal, but it is at least several years away.
Most of the work on microbicides has focused on vaginal use and has built upon spermicides, active compounds used to prevent conception. The most common spermicide is nonoxynol-9 ( N-9 ) , which is added to many lubes.
In the test tube, N-9 also seemed to have some killing power against STDs, even HIV, though clinical trials have not been so encouraging. Some community-based prevention organizations even promoted N-9 products as having some protective power against HIV during sex.
But no one had bothered to test N-9 in the rectum, not in humans, not even in animals. Last year, when the Population Council's David Phillips ran those simple tests, he was shocked by what he found. The mucosal epithelia, that single layer "skin" of cells that lines the intestines and acts as a barrier to disease, "was coming off in great sheets of cells."
Phillips found this "very troublesome" because the first line of protection was being eaten away by N-9, leaving lymph cells and others most vulnerable to infection directly exposed to HIV. His discovery led many manufacturers to stop adding N-9 to their lubricants. Many gay men, who once sought out lube with N-9, now actively avoid the remaining products with that additive.
"There is a lot of concern in our health department about N-9" for this very reason, said Connie Celum, a researcher at the University of Washington, in Seattle. She said it is time to move beyond N-9 in the search for effective microbicides.
BOTTOM LINE
"There is almost a complete avoidance" of the rectum in terms of sex and disease transmission, said Galen Cortina, a physiologist at UCLA, "It is simply a non-topic." He described the rectum as "a very poor barrier" to disease, it is "like an accordion" that can expand and contract.
Enemas and sex can cause varying degrees of damage to rectal tissue cells. One normal body response is inflammation as cytokines react to the damage. Some cytokines have the power to upregulate, or bring to the cell surface, increasing numbers of CCR5 receptors on the immune system's CD4 cells. These receptors are the prime target that HIV uses to invade the immune cells that it most likes to infect.
Maria Abreu, a researcher in bowel disease at UCLA, explained how epithelial cells are "glued together." When they are tightly packed, they even have an electrical charge that repels invaders and protects the tissue. As epithelial cells are killed off, the remaining cells flatten out to try to fill the space. This makes them more vulnerable to infection.
Peter Anton, an HIV researcher also at UCLA, said that regardless of the functional type of cell, the mucosal cells in the gut are more infectable by HIV than are blood cells. The entire gut is a primary source of HIV infection. "There are a lot of cells making more virus and each individual cell is contributing more virus," he said.
HIV infection in turn creates inflammation in the rectum, which draws the immune system's CD4 cells to the site, which are the principle cells that HIV likes to infect, and the cycle feeds on itself creating a major systemic infection. "Anything that decreases inflammation is beneficial, it might decrease viral load in the tissue," said Anton. He is looking at the use of antibiotics in that context.
RESEARCH HOPES
More than 60 compounds are under investigation for use as possible microbicides. Carraguard, derived from red seaweed and used in products as basic as Campbell's soup, is one of the products farthest along in development. Phillips and his colleagues at the nonprofit Population Council have seen promising results with Carraguard in animals and have demonstrated it is safe to use in humans. They are embarking on a large-scale clinical trial to find out just how well it works in the real world.
Another intriguing approach is to use non-nucleoside reverse transcriptase inhibitors ( NNRTIs ) , one of the three principle classes of anti-HIV drugs. Instead of making a pill, the compound would be added to a gel for use as a lubricant and the drug would kill HIV before it had a chance to enter your body.
One particular NNRTI has especially promising anti-HIV activity. Development of the compound was halted years ago when the company learned the body didn't absorb it well when taken as a pill. But that very quality of non-absorption is what you want with a microbicide that is supposed to just sit there on the tissue surface and not be absorbed.
Polly Harrison, executive director of the Alliance for Microbicide Development, says that the company that owns the patent to this NNRTI is not interested in developing it as a microbicide. But they have indicated a willingness to donate the patent rights to a nonprofit organization; a formal announcement should come shortly.
But the workshop did not focus on specific products—its broader purpose was to set a research agenda for the basic science that must underlie product development. That includes a better understanding of the biology of anal sex and better tests to evaluate how much protection a product offers.
"We don't have the anatomy of sex," lamented San Francisco sexologist Clark Taylor. "Where does semen go? What does a bowel movement [ soon after sex ] mean for protection?" Without knowing how far semen goes in the rectum and into the colon, it is impossible to know how much area needs to be protected. The answer affects things as simple as the physical volume of a microbicidal product necessary to protect the desired area.
The researchers readily acknowledged that it doesn't matter how effective a microbicide is at killing HIV if it isn't used. Thus they spent a great deal of time reminding each other that it is just as important to focus on the look, feel, smell, and taste of the final product as it is on its power to kill HIV. Taylor urged them to think of developing a microbicide as not just another lubricant, but as an "enhancement" to sex that will both reduce anxiety and increase pleasure.
The first microbicides that become available probably will offer only partial protection against HIV and other STDs. They will be a good complement to condoms, offering added protection if a condom breaks. Perhaps eventually you will be able to rely on just a microbicide for protection, but until that day comes, remember to wear your rubbers.
