As other articles in this issue of Achieve point out, the old adage of "Use a Condom Every Time" is not working. Rates of HIV infection are rising among men who have sex with men (MSM), not just in the U.S., but around the world, and especially among young MSM of color and transgender women. As Jim Eigo writes in this issue, Truvada, when taken by HIV-negative people as PrEP, can significantly lower the risk of infection. But it has two serious drawbacks: to be fully effective it should be taken every day (whether or not you're planning to have sex), and it's hugely expensive (over $1,000 a month retail).
I recall a conversation with a fellow activist years ago, as we were bemoaning the persistent rate of new infections in gay men. "It feels like we'll never get a handle on this thing until we get either a vaccine or a lube that will prevent HIV," I said. The former remains, unfortunately, years away (last April, yet another vaccine study, HVTN 505, was shut down early due to a lack of effectiveness), but the latter may be closer than we think.
Among 24,787 MSM who completed an online survey in the U.S. in 2010, 36% reported having receptive anal intercourse the last time they had sex, but only 45% said they had used a condom. Of course, it's not only gay men who have anal sex. In a 2009 U.S. survey, nearly 13% of women said they had had anal sex in the past year. That number rose to 20% in women aged 20 to 39, but only 11% said they had used condoms. Clearly, we need new tools to fight HIV, since anal sex carries the highest risk of HIV transmission among all sexual practices.
A new study, MTN 017, is looking at a rectal microbicide (RM) that contains tenofovir, one of the drugs in Truvada. Rectal microbicides are gels that are being studied to see whether they can lower the risk of HIV when used in the rectum. This Phase II study opened in October and will enroll 186 HIV-negative MSM and transgender women in Peru, South Africa, Thailand, and the U.S., including Puerto Rico. While the purpose of the study is not to prove whether the gel is effective at preventing HIV transmission, it will hopefully answer some very important questions about the gel's safety and acceptability.
First, do people like the gel? The first microbicide study to show some effectiveness was CAPRISA 004, which found that a tenofovir gel, when used by women vaginally, reduced the risk of HIV infection by 39%. Unfortunately, when that gel was used rectally in MTN 006, it caused gastrointestinal problems. So the gel has been reformulated to include less glycerin, and an earlier study, MTN-007, found that it was safe and acceptable to both men and women who used it daily for one week. MTN-017 is a larger study that will further explore the gel's safety and whether people like it, and compare it to Truvada pills.
People in the study will cycle through three regimens, each lasting eight weeks: the gel used daily, the gel used before and after anal sex, and daily use of Truvada pills. This will allow researchers not only to collect data about the gel's safety and acceptability in the rectum, but also to compare it to the use of Truvada pills, which were approved for HIV prevention by the FDA in 2012. Throughout the study, researchers will do blood tests to see if people are actually using the gel and Truvada. Similar tests done during trials of Truvada pills found that most people in the trials were not taking the drug as prescribed. But those tests were not done until the trial had ended.
"By monitoring product use as the study is underway, we will have a much better sense of whether participants are adhering to the assigned study regimens," said Ian McGowan, M.D., Ph.D., co-principal investigator of the MTN. "The unique design of our study, which does not include a placebo, allows us to address any concerns or issues with adherence in a more real-time fashion, rather than waiting until after the study has concluded." The trial should go a long way toward answering the question of whether more people will use a microbicide as opposed to a daily pill.
As we wait for the results of MTN-017 and later follow-up studies that will look at the gel's ability to lower the risk of HIV infection, we can examine the two other roadblocks to PrEP and condoms: Will gay men use it, and can they afford it?
Many studies have already looked at the first question. A 2008 survey in Peru found that of 532 MSM and transgender women who had receptive anal intercourse, 29% would prefer a pill, while 57% would prefer a microbicide (14% had no preference). Clearly, an effective RM would be popular.
Of course, we don't know exactly how the first RM will be used. Ideally, it would be similar to the lube that most people who practice anal sex already use. But to ensure accurate dosing, MTN-017 will require people to use an applicator similar to the one pictured below. A 2010 study compared the reaction of 92 men and 25 women to three different methods: an applicator, a suppository, and an enema. The authors concluded:
Among females, the applicator was the preferred product across all ages ... whereas both the applicator and the suppository were preferred to the enema among older females. ... Younger males preferred the applicator to the enema and suppository, while older males did not appear to prefer any product over another. These findings suggest that the marketing of RM products and the counseling of adherence to their use for HIV prevention may need to be age and gender specific.
But would people use an applicator when they usually use their fingers to apply lube? In Biomedical Advances in HIV Prevention -- Social and Behavioral Perspectives, Marc-André LeBlanc and Jim Pickett write:
Using an applicator to deliver an RM may be a "deal breaker." It is one thing to use an applicator in a trial; it is quite another to ask men and women ... to use an applicator in their real lives. After all, people who use lube most commonly use their fingers to apply it, utilizing the "dab will do ya method." And if more lube is needed, "another dab will do ya." ... If we are to have products that real people are going to use in their real lives, scientists and impacted communities must continue to engage with one another. Tapping community wisdom before, during, and after trials is not a luxury, or something nice to do -- it is absolutely essential.
That may depend on how effective it is at preventing HIV. Even though MTN-006 found that the vaginal form of a tenofovir gel had too many side effects when used in the rectum, it also found that people in the study reported a high willingness to use the product in the future if there was some indication of actual protection. So even though younger gay men have not seen the devastation of AIDS that was evident in the '80s and '90s, the desire to avoid infection may still be strong enough to lead them to use a less-than-100% effective RM.
When it comes to cost, condoms are of course the big winner. Not only are they cheap, they're often free, and if not are easily available over the counter. Truvada is the loser here, costing thousands of dollars a year, although its manufacturer is providing the drug free to people in the U.S. who do not have it covered by insurance or Medicaid.
Fortunately, in 2006 Gilead assigned a royalty-free license for tenofovir gel to CONRAD and the International Partnership for Microbicides. IPM has made the following statement about access:
IPM is laying the groundwork to ensure that microbicides, once developed, can quickly get into the hands of women in developing countries. New drugs have historically been designed and developed for industrialized markets, and introduced into developing countries only several years later, if at all. IPM is committed to changing this paradigm by designing microbicides specifically for women in developing countries and making them available in those countries quickly as possible.
Although we won't know until the first RM is approved, there's good reason to hope that such a product will be far closer in cost to condoms than to Truvada.
Unfortunately, it's unlikely that any RM will be as easy to obtain as condoms. The FDA will most likely require that an RM like the one being tested in MTN-017 be available by prescription only, to ensure that people using it have tested HIV negative. That's an extra, but not insurmountable, hurdle in the U.S. If the Affordable Care Act increases the number of people who have health insurance it may become much smaller. Still, it will not be as simple as picking up a tube of KY jelly at the drugstore. In other countries, groups like IPM will be working to make access as widespread as possible. And we need to keep searching for an RM that does not contain any HIV meds, so that people with HIV who have receptive anal sex can use it to protect their partners. That's not recommended for RMs that contain HIV meds.
The first RM will also have to be marketed effectively. According to Jim Pickett, "I think when we do have an RM, it will be best to market it first and foremost as HIV prevention. It should be marketed as a sexy, fun lube that happens to offer protection. It absolutely should not be called a microbicide -- we need to create desire and have people want to use the product because it is pleasurable. That word doesn't conjure desire -- so it will need to go."
Harriet Langanke, director of the German Sexuality and Health Foundation, adds, "To encourage microbicide adherence among these populations, first, the microbicide must be shown to work and the protection must be effective. Availability is a significant issue, as these products must be easily at hand, at least as easily available as the male condoms, and when it comes to marketing, the product packaging itself has to either be very discreet or evoke a positive image."
Since RMs may never be as effective as using a condom every single time you have sex, one barrier to its use could be the stigma that we are currently facing with Truvada for HIV prevention. Many people, even in the gay community, can't understand how people can put themselves at risk for HIV when such a cheap, effective tool as the condom is readily available. Gay men can have a hard time admitting to their doctors that they're being unsafe, and that can be even harder to admit to peers. Carrying an RM with you for casual sex could carry the same stigma that condoms hold for some now. "If you don't have HIV, why do you have this kind of lube? Do you think that I do?" We've had to fight these battles for men using PrEP, and we need to find ways to avoid the same ones being waged when it comes to RMs.
Rectal microbicides, like condoms and PrEP, are not going to be the ultimate answer to stopping HIV. Even the first FDA-approved HIV vaccine will probably not be 100% effective. But, if proven safe and effective, and when used in combination with other methods, it is hoped that RMs will soon make a significant difference in turning around the stubbornly high infection rates we live with now. The important thing is to start asking the questions about them now, so that when the first one does emerge, we're ready to use it in to maximum effect.
Mark Milano is the Editor of Achieve.