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Rectal Microbicides

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Who needs Rectal Microbicides?

Heterosexual men and women, gay men and males who have sex with males practice anal intercourse (AI) for pleasure. Heterosexuals may also practice AI to avoid risk of pregnancy or to “maintain virginity”. The few international studies available show that anal intercourse occurs all over the world – with heterosexual couples engaging in AI in many cultures. In the UK and US, between 10% and 35% of heterosexual women report practicing receptive AI, and lifetime reports of AI with opposite-sex partners are as high as 40% for US males. A conservative estimate is that seven times more heterosexual women than gay man in the US practice receptive AI.

Receptive sex partners (whether women or men) are 10 to 100 times at higher risk of HIV infection than insertive partners during unprotected intercourse. But both partners can be exposed to other sexually transmitted infections (STIs) including anal warts, hepatitis B, syphilis and gonorrhea. Condoms provide an effective barrier against infection but millions of receptive sex partners can't or don't insist on condoms every time.

Currently in development, rectal microbicides are products that might reduce the transmission of HIV when used during anal intercourse (AI), they could offer protection in the absence of condoms as well as additional protection when condoms are being used. For those unable or unwilling to use condoms, rectal microbicides could be a safe and effective alternative means of reducing risk, especially if they were unobtrusive and/or enhanced sexual pleasure enough to motivate consistent use. Such alternatives are essential if we are to address the full spectrum of prevalent sexual practices and the basic human need for accessible, user-controlled HIV and STI prevention tools.

What's the difference between vaginal and rectal microbicides?

Although more than 50 potential microbicides are being investigated for possible vaginal use, it's not clear yet which of them will be suitable for rectal use. The rectum and the vagina differ significantly in structure and natural ecologies. The vagina, for example, is a closed pouch while the rectum is part of an open-ended cavity. A greater quantity of the microbicidal product is likely to be required for adequate rectal coverage than will needed for effective vaginal use. The rectal lining is more fragile than most of the tissue lining the vagina. It is also richer in CD4 receptors, cells particularly vulnerable to HIV infection. These factors further enhance rectal vulnerability to irritation, tearing and infection during sex.

 

Researchers seeking for clearer answers

Although most microbicides research is now focused on vaginal use, research and development of rectal microbicides is a growing segment in the field.

Researchers are now seeking answers to questions about:

  • How does HIV infection occur in the rectum?
  • How do we design tests that will give us this essential information?
  • What happens to the microbicide once it is inside the rectum?
  • What kind of application method are people willing to use?
  • What happens if someone inserts a vaginal microbicides (once available) rectally?
  • Is it possible to design a safe and effective rectal microbicide?
  • What concentration provides the most protection without causing damage to rectal tissue?
  • How long does it need to remain there? How far in advance of sex can it be applied and still work?
  • Since a product inserted rectally can travel up into the colon, how much of a microbicide product may be needed to cover the rectal walls most exposed to semen
  • What are other factors related to acceptability need to be considered?

Rectal microbicide research is starting to happen

Rectal microbicide research and development includes several types of research that seek answers to some of the questions mentioned above.

General baseline studies (phase 0) measure the baseline levels of injury and inflammation that occur in the rectum during typical anal intercourse.  In 2005, data from University of California Los Angeles (UCLA) contributed substantially to the development of a baseline picture of the regular ‘wear and tear’ that anal intercourse causes in the body, and this information is essential to further study the effects of microbicides on anal tissue.  In 2007 researchers at UCLA completed a study that established for the first time the most stable measures that could be used in studies of candidate microbicides used rectally.

Distribution studies then look at how a microbicide might travel and be distributed during and after sex. Initial results suggest that four hours after sex, both the “semen” and “microbicide” have traveled 60 centimeters (approximately two feet) up the colon. This data is critical for setting the parameters for measurement in clinical trials (Find out more information on how clinical trials are being conducted.)

The first Phase I clinical trial was conducted at UCLA to test the safety and applicability of an ARV-based microbicide (UC-781) for rectal use, using the vaginal microbicide gel formulation. "Male Tolerance" trials are also being done to see if irritation occurs on the penis or within the male urethra when exposed to various potential microbicides. And acceptability or behavioral studies are beginning to learn what kinds of products people might be willing and able to use.

Three additional Phase I rectal safety studies are planned to start in 2009. The first study would evaluate the rectal safety profile of PRO 2000 in sexually active HIV-negative and then HIV-positive men who have sex with men (MSM).  The second study would look at the safety of the vaginally formulated 1% tenofovir gel applied rectally, and measure how the drug is distributed and retained in the body (its pharmacokinetics). It would also include a comparison of topical with oral tenofovir levels in rectal tissue, rectal fluid, and blood. The third study in development would evaluate tenofovir topical gel in both men and women who practice receptive anal intercourse.

What about using vaginal microbicides for anal intercourse?

It is essential that all vaginal microbicides candidates in late stage clinical testing be tested for rectal safety, because it is likely that people will try to use them rectally in the hope of gaining some protection. A product may be very safe for vaginal use while unsafe (and increasing the risk of infections) for rectal use. Rectal safety is essential so that any such products that are NOT safe for rectal use can be labeled in a way that specifically indicates what the consequences of using them rectally may be.

What we know now:

How people use sexual lubricants can tell us a lot about what they want in a rectal microbicide.

The majority of people engaging in anal intercourse use lubricants. Our knowledge of the lubricant market and factors that contribute to product acceptability must inform work to develop rectal microbicides that are acceptable, as well as safe and effective, when used in "real life" circumstances.

Nonoxynol-9 isn't recommended for use as a rectal microbicide

Approved by the regulatory authorities as a spermicide, Nonoxynol-9 (N-9) is the active ingredient in most over-the-counter birth control products. It was added to many sexual lubricants when studies showed that N-9 kills HIV as well as sperm. In one US study, 41% of men using sexual lubricants for anal intercourse said they bought lubricants containing N-9 because they thought using such products would reduce their risk of HIV infection.

Unfortunately, that is NOT true. N-9 can irritate both rectal and vaginal tissues, thus making it easier for HIV to get into the blood stream of the receptive sex partner. In a study conducted by the Population Council, lubricants containing N-9 were shown to strip surface cells off of the rectal lining, potentially enhancing its vulnerability to infection. For this reason, the Population Council, the CDC and many other health promoters strongly advises against the use of sexual lubricants containing N-9 during anal intercourse.

Over-the-counter lubricants now available aren't proven microbicides.

Some researchers have been looking at the "over-the-counter" lubricants available in pharmacies and "sex shops" to see if they might work as microbicides. Three of these commercial products have been shown to kill HIV in a test tube. However, commercial lubricants often contain preservatives, perfumes and other ingredients that could cause irritation if applied internally on a regular basis and/or in large quantities.

No research data are yet available to tell us which lubricants may be safe to use as microbicides and which are not. As we learned with N-9, it is risky to make assumptions about a product's safety or effectiveness before the research on it is complete. There is no proof that any of the available over-the-counter lubricants are either safe or effective as microbicides.
 

We need safe and effective rectal microbicides. The time to develop them is now!

Significant biological, sociocultural, and political barriers have hindered necessary research and development of a safe and effective rectal microbicides. But we must not delay efforts to develop these urgently needed products. The escalating numbers of new infections resulting from unprotected anal intercourse testify to the fact that having one prevention tool, condoms, just isn't enough. It is time to for receptive partners of both genders to have methods they can control. It's time for rectal microbicides.

How can you get involved in advocating for these urgently needed products?

The International Rectal Microbicide Advocates is a coalition of over 800 advocates, policymakers and scientists from 46 countries on 6 continents to advance a robust rectal microbicide research and development agenda. To get involved, join the listserve, or learn more, visit www.rectalmicrobicides.org or contact Jim Pickett at JPickett@aidschicago.org


LessSilenceMoreScience

Less Science More Science: Advocacy to Make Rectal Microbicides a Reality - advocate for more science and end the silence around the lives of so many. (Tambien esta disponible en Español - Menos Silencio, Más Ciencia)

This document will:
- Serve as an authoritative reference on recent developments and current efforts in rectal microbicide research;
- Illustrate key advocacy goals and strategies;
- Provide a description of the resources and activities of IRMA; and,
- Inspire people working in HIV prevention, whether in advocacy, research, policy or funding, to become involved in rectal microbicide advocacy and research.