Men and Women Demand Rectal Microbicides
Recent scientific developments have both inspired and challenged everyone engaged in the fight against AIDS. Much-needed new methods of HIV prevention have been shown to work. But while there has been much excitement, there has also been significant concern and controversy.
For more than 30 years, the belief was that "safer sex = condoms". But what happens when science shows that pills and gels can also prevent HIV? How do we rethink decades of prevention programs that equated condoms with safer sex and left few other choices? What does "protected sex" mean now? And how has the definition of "unprotected" sex changed?
Of course, condoms work really well -- when they are used consistently and correctly. But for a host of reasons, condoms often stay in the wrapper even when people know better. Several studies report that about 50% of gay men in the U.S. use condoms regularly, and that number is only around 25% among heterosexuals.
One could argue that we've reached our limit with condom promotion. For U.S. gay men, we've seen 50% use for decades now. Condoms alone are clearly not up to the task of preventing enough infections to turn the HIV epidemic around. In reality, no single option can ever end this epidemic. There will never be a "magic bullet". Indeed, there is nothing magical about HIV prevention!
Three Years of Change
Around 8 million people worldwide are now receiving lifesaving HIV treatment. Nearly 7 million more are eligible but not yet on treatment. At the same time, 2.5 million people became infected in 2012, and almost 2 million people died due to AIDS in 2011. Imagine the fourth largest city in the U.S., Houston, emptied -- wiped off the map.
Around the world, more people need to know their HIV status. And we must link those who test positive to care. We must also link those who are negative to the widest possible range of prevention options. Yes, we need to continue promoting condoms. But we also need to expand people's options.
In mid-2010, a microbicide gel containing an HIV drug called tenofovir showed a modest benefit in preventing HIV infection in a study of South African women who applied the gel before and after sex. Later that year, a global trial in gay men and transgender women showed that the HIV med Truvada could prevent HIV infection when taken once a day -- a strategy called PrEP (pre-exposure prophylaxis). But two other studies showed that PrEP did not work because people did not actually take the pill every day. When the FDA approved Truvada for PrEP in July 2012, it was a moment to celebrate science -- the first new HIV prevention tool since the FDA approved the female condom in 1993! It was also a moment to look at the hard work needed to make prevention work for people.
The State of PrEP
PrEP is starting to be implemented, though very slowly. While studies have shown that it can work, we need to understand who can benefit most, how to use it safely and efficiently, how to integrate it with other methods such as condoms, and how to maintain high levels of adherence, which research has shown to be essential for PrEP to work properly.
Challenges include ensuring that PrEP will not hurt access to HIV drugs for people with HIV, identifying who could most benefit (many of whom don't have access to health care), finding the money to pay for it, and educating insurance companies, government programs, health care providers, and individuals about its benefits and limitations.
We know daily Truvada is not for everyone. So we must continue to research the next generation of prevention options. Here are some of the questions being explored:
- Can taking a pill every few days instead of daily, or only when you might be exposed, still provide protection?
- Would women prefer to use a vaginal ring containing an HIV drug that only needs to be replaced once a month?
- Can a once-monthly injection of an HIV med provide enough protection?
The pipeline of longer-acting, easier-to-take prevention products needs to move swiftly. Several vaginal rings are currently in development. There are also early trials of long-acting injectable drugs. The history of family planning teaches us that more people use protection as the choices expand.
Until recently, microbicide research has focused on vaginal microbicides. If scientists and advocates considered rectal microbicides at all, it was strictly in the context of the need to test vaginal products for rectal safety, since an approved vaginal microbicide would likely be used in the rectum as well.
But anal intercourse is common among both gays and straights, and is a significant factor in the spread of HIV. In the U.S., the majority of new HIV infections can be attributed to unprotected anal intercourse among gay men. Due to the biology of the rectum, unprotected anal intercourse is 10 to 20 times more likely to result in HIV infection compared with unprotected vaginal intercourse.
Initially, the majority of the HIV community -- scientists and advocates alike -- dismissed the possibility of a rectal microbicide that was safe and effective. Its pursuit seemed hopeless, even laughable.
Biological challenges played a role in this lack of enthusiasm. The vagina is essentially an enclosed pouch, whereas the rectum leads to about five feet of colon, which is a lot of territory for a microbicide to cover. The vaginal lining is approximately 40 cell layers thick, while the rectum's lining is only one cell layer thick. The rectum also has a large amount of cells that HIV directly targets. Protecting the vagina from HIV infection seemed possible -- protecting the rectum appeared much more difficult, maybe even impossible.
Politics and culture reinforced the dismissal of rectal microbicides. Pervasive homophobia has resulted in a lack of adequate resources devoted to gay men, including in the U.S. People also wrongly assumed that anal intercourse was exclusive to gay men, and that women would not need a rectal microbicide. So why develop a specific prevention tool for an ignored or hated population?
Despite this array of challenges, and despite low funding for rectal microbicide research, the field has moved from being simply an adjunct to vaginal research to a force in its own right. This is due to a handful of visionary, passionate, and dogged scientists; funding from the U.S. (which has supported the lion's share of rectal microbicide research); and community advocacy.
Small Phase I trials, designed to determine whether products are safe and if people actually like using them, have led to the first-ever Phase II trial of a rectal microbicide. In the first half of 2013, the MTN-017 trial of a tenofovir gel is set to launch in the U.S., Thailand, South Africa, and Peru. The gel is similar to the gel being studied among women in Africa, but has been modified to be more "rectal friendly".
The 186 gay men and transgender women in this trial will more than double the total number of people who have participated in all rectal microbicide trials to date. Also, the trial is the first to include sites outside the U.S. The study will investigate the safety and acceptability of the gel, and will compare it to daily PrEP. Everyone in the trial will try three different regimens, each lasting eight weeks. In the first regimen, people will apply the gel to the rectum daily. In the second, they will apply it before and after anal intercourse. In the third, they will take Truvada daily, with no microbicide. The order in which participants will follow the regimens will be assigned by chance, with a rest period between each one.
The study will also look at how much of each drug is absorbed in the blood and rectal tissue, and will look for changes in cells or tissues. People will be asked about any side effects, what they liked and disliked about using the gel either daily or with sex, and whether they would use it in the future. The results won't tell us whether the product works to prevent HIV. But this important study could lead to another first: the launch of a large-scale trial to test whether a rectal microbicide can prevent HIV infection.
What Do We Need?
Advocacy around rectal microbicides needs to concentrate on a variety of things. One of the most important priorities is adequate funding, especially as the field moves toward large-scale trials. Funding is important for earlier phases of research as well, and to support laboratory studies, where new products are dreamed up. We also want a variety of microbicides to choose from, and a variety of ways to apply them. Women want microbicides that also provide birth control. And we need microbicides that protect against other sexually transmitted infections, not just HIV.
People with HIV want microbicides, too. But they may not be able to use ones based on HIV drugs, as that could interfere with their own treatment. We need microbicides without HIV meds. Positive folks want choices for protection too!
Finally, there is a strong desire to have microbicides that work in both the vagina and the rectum. We need products that are safe and work wherever you put them, whether you have anal or vaginal intercourse. Plenty of women have both, so providing one microbicide that could be used for both would be best. Having one product would also reduce the stigma associated with anal sex. People may be afraid or ashamed to ask for a rectal microbicide because that could label them and cause discrimination and even harm.
For this reason, rectal microbicide advocates have also prioritized education efforts, to reduce the ignorance and stigma associated with anal sex. Promoting anal health and wellness is also important. It is a part of our body many of us prefer to ignore -- out of sight, out of mind. But that's not a good recipe for keeping the anus healthy. We all have one, and we all should have one that is healthy!
HIV prevention is complicated and controversial. Whenever you talk about sex, there will be strong reactions. Now that we have these new methods, and more strategies on the way, we're seeing lots of powerful positive and negative feelings about the idea of expanding our prevention toolbox to make room for but new approaches.
"New" can be threatening. "New" takes us into uncharted territories. There is a lot we don't know about something that is new, and that can be frightening. But prevention advocates must fight for more choices, so people have more opportunities to have sex that is protected. That is what this is all about -- condoms for some, pills for others, and gels, rings, injections, and future things we can't yet imagine for others.
The prevention "buffet" has basically consisted of one thing -- let's say potatoes -- for the last 30 years. Plenty of people like potatoes. Others enjoyed them for awhile, but are now skipping the buffet because they are sick and tired of potatoes, potatoes, potatoes. Others never liked potatoes in the first place, never ate them, and never will -- no matter how hard we try to make those spuds appealing.
So the answer is "yes" to potatoes. And "yes" to other tasty things to reach the non-potato crowd. No one should go hungry. And no one should only have one option to protect themselves during sex.
Jim Pickett is Chair of IRMA (International Rectal Microbicides Advocates). Mitchell Warren is the Executive Director of AVAC.