1. Rectal Microbicides: New Hope for HIV and STD Prevention
[Notes to speakers are bolded and in square brackets.]
[Please start off by introducing yourself and your organization. Say why you are making this presentation and why this issue is important to you. Then you could say something like:]
Many of you may be familiar with vaginal microbicides – products that are being developed to help prevent HIV transmission when applied in the vagina
In this talk, I will be updating you on another category of microbicides – something that a handful of scientists and advocates around the world are working on – microbicides for rectal use.
The slides I will be using are provided by the Global Campaign for Microbicides – and are actually available for download on their website. The Global Campaign is a coalition of over 250 organizations worldwide that works to accelerate development of -- and widespread access to -- safe and effective microbicides and other user-controlled methods of HIV prevention. You can get more information through the Campaign’s website at
[We suggest you go to the web site before your presentation and download material (including fact sheets about N-9 and rectal microbicides) to use as hand-outs at your presentation. You’re welcome to copy and distribute anything on our web site.]

2. Objectives Why we need rectal microbicides
What is involved in development
Where the research is
What you can do to get involved
I’m going to try to do a few things in this presentation:
First, I’m going to talk about rates of anal intercourse and why both men and women need rectal microbicides.
Then, I will talk about the process being used to develop rectal microbicide and give you some specific examples of recent or on-going research. Developing and testing products that are safe enough to insert into the rectum but effective enough to reduce the risk of infection is a pretty big challenge, as you will see.
I’ll discuss why we need to start making some noise about needing rectal microbicides. When these new products become available doesn’t just depend on the scientists. It also depends on us and how loudly we’re willing to demand them. Just as we had to fight for more and better AIDS drugs in the 1980s and 1990s, we have to fight for access to microbicides now. We’ll talk about why that is and how you can get involved.
At the end of the talk, I’ll tell you about some exciting initiatives that groups around the world are undertaking – and what you can do if you want to be part of this advocacy.

3. Men at risk
High rates of condom use are difficult to maintain, as the rate of new HIV infections shows
New data reveals reasons for concern:
UK: 48.8% UAI in the past year
US: 30% UAI (HIV - men in past year)
STD rates confirm UAI prevalence
Access to antiretroviral therapies have dramatically reduced the number of AIDS-related deaths occurring in the US, Canada and Europe over the last decade. But these drugs have not stopped – or even slowed down -- the rate of new infections. People continue to have unprotected sex in many populations. The rates of unprotected anal sex among men who have sex with men (MSM), for example, is pretty well documented.
In the UK, the Gay Men’s Sex Survey of 16,000 men who have sex with men showed in that almost half (48.8%) of all respondents had engaged in unprotected anal intercourse in the last year.1 Even more alarming is that nearly 15% (14.59%) of the respondents who were HIV negative or hadn’t been tested for HIV said they had definitely, or probably, had unprotected anal sex with a man they thought was HIV+ in the last year.
In a 5 city study of HIV negative MSM (called the EXPLORE study), HIV negative men report 70% condom use during anal intercourse in the past year – in other words, 30% of these HIV negative MSM had unprotected anal intercourse in the past year.2
Finally, reports from several countries around the world showed increases in unprotected anal intercourse, sexually transmitted infections, and HIV incidence among MSM.
These studies tell us that we need better prevention education and condom use promotion. They also tell us that we need more prevention alternatives to help men who simply aren’t using condoms consistently reduce their risk of infection.
1: Out and about. Findings from the United Kingdom, Gay Men’s Sex Survey Sigma Research
2: Koblin BA, Chesney MA, Husnik MJ, Bozeman S, Celum CL, Buchbinder S, Mayer K, McKirnan D, Judson FN, Huang Y, Coates TJ; EXPLORE Study Team. Related Articles, Links High-risk behaviors among men who have sex with men in 6 US cities: baseline data from the EXPLORE Study.  Am J Public Health Jun;93(6):

4. Women at risk
In large US survey, 35% of women age report having had anal sex at some time in their life
32% of high-risk women reported anal sex in past 6 months (Gross et al, 2000)
Some people think the issue of rectal microbicides is only relevant to a small segment of the population -- men who have sex with men. But that’s not true! Anal intercourse is practiced by both heterosexuals and homosexuals for many reasons – including pleasure and as a way of having intercourse without risk of pregnancy.
In a US sample of 12,571 men and women between 25 and 44, 97% of men and 98% of women said they had experienced vaginal intercourse. 90% of men and 88% of women had experienced oral sex with an opposite-sex partner; and 40% of men and 35% of women had experienced anal sex with an opposite-sex partner. 1
In another federally-funded study in the US, 32% of the high-risk women participants reported having had anal sex in the past six months. The small amount of international data available on the topic show that anal intercourse is also practiced in various populations all over the world. 2
In a U.S. study of 18 to 24 year old women in a neighborhood with widespread injection of drugs and HIV, 14% reported unprotected anal sex with men in the past year. 3
Receptive sex partners (whether women or men) are at higher risk of HIV and STI infection than insertive partners during unprotected intercourse. So the issue of how people protect themselves during anal intercourse is very much a women’s -- as well as a men’s --- issue, and a straight -- as well as a gay -- issue.
1: US National Survey of Family Growth - Mosher WD, Chandra A, Jones J. Sexual behavior and selected health measures: Men and women 1544 years of age, United States, Advance data from vital and health statistics; no 362. Hyattsville, MD: National Center for Health Statistics
2: Anal Sex Among HIV-Seronegative Women at High Risk of HIV Exposure. JAIDS Journal of Acquired Immune Deficiency Syndromes. 24(4): , August 1, 2000.
3: Friedman, Samuel, et al AIDS: Volume 15(15) 19 October 2001 pp

5. What is a microbicide?
Microbicides are substances that can reduce the transmission of HIV and other STD pathogens when applied vaginally and, possibly, rectally.
They are not yet available.
Now, let’s talk about microbicides. When we say “microbicide”, we mean any substance that can safely and effectively reduce risk of sexually transmitted diseases, including HIV, when it is applied in the vagina or rectum.
It’s important to understand that there aren’t any proven microbicides on the market yet. What we’re talking about here today are products that are now under development.
The first generation of vaginal microbicides could be available in some countries by as soon as These are expected to look a lot like the over-the-counter birth control products we already know -- the gel, foam and cream-type products that are inserted with applicators. This picture shows what some of the applicators are expected to look like.
Remember, these are products designed for vaginal use, so the applicators are very similar to the ones used for vaginal contraceptive products now.
Currently, they are formulated as lubes, gels or creams applied with an applicator like those shown here

6. We need a product that is…
Inexpensive
Easily accessible (over the counter)
Easy to use
Safe, non-irritating
Available in various forms (in lubes, suppositories, on condoms)
Effective
But what will rectal microbicides be like? Most people would agree that they’d like a product that is inexpensive, easily accessible without a prescription and simple to use.
Obviously, we need products that are safe and don’t irritate either the rectum or the penis. Irritation, inflammation or allergic reaction to any product can actually increase HIV and STI transmission risk because it makes it easier for pathogens (germs) to enter the bloodstream. So it’s critical to have products that are safe, even when they are used several times a day.
We’ll also need rectal microbicides that come in various forms. Putting them in lubricants makes sense because most people use lubes during anal sex anyway. But some people may want time-released products than can be inserted in advance, like a suppository. And some may want a microbicidal coating on their on condoms – to provide extra protection in case the condom breaks or slips.
Naturally, everyone wants effective products. In a recent survey of 385 men in West Hollywood, California, respondents on average said they wouldn’t use a rectal microbicide without a condom unless it were at least 84% effective against HIV. 53% said the microbicide would have to be at least 95% effective before they would consider using it without a condom.1
These results raise an interesting question. We estimate that the first vaginal microbicides, when they come on the market, will be about 60% effective. Obviously, that’s nowhere near as protective as a condom and folks who are using condoms should continue to use them.
But let’s say there is a partially effective rectal microbicide…What would you say to a friend who tells you he is barebacking and asks you if he should try these new microbicides? Would you urge him to give them a try? Or would you say they’re not safe enough and urge him to use condoms? [This is a good point for audience discussion]
1: Gary Marks, Gordon Mansergh, Nicole Crepaz, Sheila Murphy, Lynn C. Miller, Paul Robert Appleby, Future HIV Prevention Options for Men Who Have Sex with Men: Intention to Use a Potential Microbicide During Anal Intercourse, AIDS and Behavior, Volume 4, Issue 3, Sep 2000, Pages 279 – 287.

7. What if we had a complete HIV toolkit?
Prior to exposure
Point of transmission
Treatment
Rights-focused behaviour change
Voluntary counselling and testing
STI screening and treatment
Preventative Vaccines
Pre-exposure prophylaxis (PREP)
Male circumcision
Male and female condoms and lube
ART to prevent perinatal transmission
Clean injecting equipment
Vaginal and rectal microbicides
Cervical barriers
Post-exposure prophylaxis (PEP)
Improved antiretroviral therapy
Treatment for opportunistic infections
Basic care/nutrition
Prevention for positives
Education and behavior change
Therapeutic vaccines
If microbicides were available right now, how would we change the HIV and STI prevention messages we give out?
Condoms will remain the option of choice in terms of effectiveness -- provided they are used correctly every time. But, as you see here, microbicides also have a natural place as one option in the Prevention Spectrum. We’ve shown the existing prevention strategies in black here and the ones now being developed and tested in red.
Behavior change will remain an important way for people to protect themselves prior to being exposed to HIV. When an effective HIV vaccine becomes available, it will substantially strengthen our ability to take action in this pre-exposure phase.
Neither vaginal or rectal microbicides will replace condoms or the means used to prevent mother-to-child transmission of HIV. These will remain essential strategies to help prevent infection from occurring at the “point of transmission” phase of prevention. Instead, the microbicides add another valuable option to the array we already have – an option that will give people who can’t or don’t use condoms (for whatever reason) a way to reduce their infection risk.
So, to present them fairly, we will have to adopt a hierarchical prevention message – one that looks like a ladder or a sexual version of harm reduction messages that you might know. We will need to put condoms at the top and strongly encourage consistent condom use – emphasizing that it’s the best protection. But microbicides would give us a second-best option when people can’t or decide not to use condoms.

8. Why vaginal microbicides?
Women currently have no way to protect themselves when her partner won’t use a condom
Women biologically more vulnerable to HIV
2-4 times more likely than men to get HIV from vaginal sex
Women may be less able to assert their rights
Current methods (abstinence, fidelity, and condom use) often require male consent, knowledge, or cooperation
I am going to spend the next few minutes talking about vaginal microbicides because the research to develop vaginal microbicides is further along and there is a lot we can learn from this progress.
The first generation of microbicides could be on the market by the end of the decade. But these will be products designed for women to use in their vaginas – not for rectal use. Microbicide researchers have made developing a vaginal microbicide their #1 priority because, right now, there’s nothing a woman can use to protect herself during sex that’s completely under her control.
Millions of women around the world are getting HIV because they simply don’t have the social or economic power to insist that their male partners use a condom every time. So women urgently need a way to protect themselves form infection that doesn’t rely on male cooperation.

9. Vaginal Microbicide Research in 2005
Laboratory Testing
2-6 Years
Phase 3
(efficacy)
2 to 4 Years
Simultaneous studies in some cases:
HIV+, penile & rectal safety
10 or more years
5 products
3 products
6 products
10-20 products
Phase 1
(safety)
1 to 6 Months
Phase 2
Up to 2 Years
25 – 40 people
people
3,000-10,000 people
As you see, the process of developing a new drug often takes more than a decade. Before anything can be tested in humans, the developers have to show that (a) it’s not likely to be harmful to humans and (b) it may be beneficial. That research is done in the laboratory and can take from 2-6 years.
If a product is approved for human trials, it goes through a series of Phase I safety trials, each taking between 1-6 months. Next it undergoes Phase 2 trials to gather extended safety data. If the product is shown to be safe, they test to see if it is effective. The Phase 3 effectiveness trials can take 2-4 years because a large number of participants are enrolled. Each participant gets a year or two of follow up services, to see if the product has any effects after extended use. It may be necessary to do more than one Phase 3 trials before a product is fully proven to be effective.
While these trials are going on, in some cases, researchers also start separate trials to look at whether the product is irritating to the penis, how the body will react if the product is inserted rectally, and whether it is as safe for HIV positive people to use as it is for HIV negative people.
It can take another year or two for the product to be considered by regulatory authorities and, if approved, go to market. Five vaginal microbicide candidates are now in Phase 3 trials. If any one of them turns out to be effective, it could be publicly available in 5 years.
But this is a “best case” scenario. If none of the candidate products now in Phase 3 proves to be effective, we will have to wait longer. How long we have to wait depends, in part, on how fast we can keep new products advancing in the pipeline.

10. How could microbicides work?
Kill/inactivate/immobilize the virus
Boost body’s natural defenses
Prohibit viral entry by blocking fusion
Inhibit viral replication
Create a physical barrier
or some combination of these approaches
Vaginal and rectal microbicides could work in similar ways.
The first approach they’re using is pretty obvious -- coming up with products that just kill or disable HIV and other pathogens that come into the body. The trick here, of course, is to make something that kills pathogens but doesn’t irritate the epithelial lining of the vagina or rectum. Some products in this category are in vaginal trials but none are in rectal trials yet. Since the rectum is more fragile than the vagina, it may be difficult to create a product with this mechanism of action for the rectum.
The second approach involves trying to enhance the body’s own ability to protect itself. One product in this category, called BufferGel, is designed primarily to keep the vaginal pH low even after ejaculation -- since low pH is one of the vagina’s defense mechanisms. A low pH can inactivate a substantial amount of HIV entering the body, as well as some other pathogens. Although rectal pH is naturally higher than vaginal pH, the creators of BufferGel feel that their product might still have some efficacy in reducing HIV risk in the rectum. Research is needed to see if the rectum can tolerate BufferGel without problems. In the test tube, BufferGel appears to inactivate not only HIV but also chlamydia and Human Papilloma Virus (HPV).
The third approach involves creating products that make a barrier to keep pathogens, like HIV, from attaching to epithelial cells. We know that HIV has to attach to a cell in order to infect it. If it can’t attach, it can’t infect
A fourth approach is to take some of the anti-retroviral drugs that many people with HIV take to reduce viral load and re-formulate them for topical use in the vagina or rectum. Products in this category are just going into vaginal trials but none are in rectal trials yet.
In the end, we will ideally be able to combine these mechanisms for greatest effectiveness.
(More details available from the Alliance for Microbicide Development –

11. Physiological Differences
Vagina
Rectum
Most of the epithelium is 40 cell layers thick
Very fragile epithelium,
1 cell layer thick.
Fewer CD4 cells than rectum
More inflammatory cells under surface
(CD4 receptors)
Acidic pH
Alkaline, rather than acidic pH
Enclosed pouch
Open-ended tube
There is a lot to learn from research into vaginal microbicides, but there are also critical differences between making a microbicide for vaginal and one for anal use.
Most of the vaginal wall is many cell layers thick. Rectal walls, however, are a single cell layer thick. The cells in the rectal wall also contain a lot of CD4 receptors making them especially vulnerable to HIV. Rectal tissue is also spongy and highly absorbent – unlike vaginal tissue which is designed to resist pathogens.
Overall, rectal tissue is more fragile than vaginal tissue. So, if a product is not well tolerated in the vagina, it is highly unlikely to be well tolerated in the rectum.
A healthy vagina also protects itself by maintaining a slightly acidic pH which helps to prevent the growth of pathogens. The rectum, on the other hand, tends to be slightly alkaline. So it doesn’t have that protection either.
Finally, the rectum isn’t a closed pouch like the vagina. It takes about 3-5 ml. of product to coat the inside of the vagina—that’s what was in the applicators you saw in the earlier slide.
The rectum, on the other hand, is the final part of the digestive tract. A product inserted rectally can travel up into the colon. This means that significantly more product may be needed to protect the rectal walls where they need protection. One of the key questions scientists are trying to answer now is exactly how much product it will take and what areas have to be covered to get a good protective effect.
All these factors make it substantially more challenging to create a safe, effective rectal microbicide than it is to make one for vaginal use.

12. Anatomy 101
This picture1 helps us visualize the area we are talking about and what tissues are likely to be exposed to a rectal microbicide.
Imagine, for example, that you were applying a microbicidal gel with an applicator or using a dissolving suppository. It would be inserted through the anal opening into the rectum. Right away you can see how the squamous mucosa – the thicker tissue around the anus – thins out inside the body. In the rectum, the tissue becomes more delicate and spongy.
From there, the product is likely to travel up to the sigmoid colon. In a few minutes, I’ll talk about “distribution studies” that were done to see exactly how far a product like this would be likely to travel up into the descending colon. The researchers found that a gel the consistency of semen could travel as much as 60 centimeters (approximately two feet) up the descending colon.
This certainly tells us the safety has to be a primary issue in rectal microbicide development. It will be quite challenging to find a product that can be applied repeatedly to the fragile tissue of the digestive track without damage – yet will be capable of inactivating HIV once it’s there.
1. Image source:

13. Research questions
Infection – more to learn about anal intercourse and HIV infection
Testing - What assays (tests) to measure impact?
Distribution – how would it spread?
Application Methods?
Dosing – how much, what is acceptable?
How does rectal shedding of HIV impact risk?
Along with product distribution, there are a number of other questions that also have to be answered. Researchers are now seeking answers to questions about …
HIV Infection: There is still more to learn about how HIV infection occurs in the rectum.
Testing / Assays: How do we design tests that will give us this essential information? For example, how do we measure how well the product stays in place, how much of it is absorbed into the bloodstream and how it gets moved around during sex? MRI scans have been shown to be an effective tool for look at how products move around in both the vagina and the rectum.
Distribution or dilution: What concentration of product can give the most protection against HIV and other STIs without causing damage to rectal tissue? What happens to the microbicide once it is inside the rectum? How long can it dissolve and spread out before it becomes ineffective?
Application methods: How a product is applied will influence both its acceptability and level of protection. Will people be willing to use gels inserted with applicators, anal douches, suppositories that dissolve over time, lubes or other products applied to the penis?
Dosing: How do various products feel and how much can one apply before causing rectal “fullness” and discomfort? Different formulations will cause different sensations and will coat the rectal walls differently. So dosage acceptability and coverage issues have to be studied.
Rectal shedding of HIV: What impact would a microbicide have on HIV that is already in the rectum of an HIV positive partner. And how will that affect the insertive partner’s risk of becoming infected or re-infected by the receptive partner during intercourse?

14. Laboratory research To learn more about:
How HIV infection occurs in the rectum – what cells are most vulnerable
The impact of intercourse on rectal tissue (trauma, inflammation, speed of healing)
What markers can we look at to determine impact of a product on the rectum?
Several kinds of research are underway to find answers to some of these questions. The first kind is called pre-clinical research. This refers to studies that are done in the lab. In pre-clinical trials, scientists are figuring out exactly how HIV infection most commonly occurs in the rectum. They have to know which cells are most vulnerable before they can design products specifically to protect those cells and block infection.
All the potential rectal microbicides identified so far are still in this pre-clinical stage. None of them are in human trials yet – although the first one may start in late 2006.
Baseline research also has to be done to learn how the body functions during and after intercourse -- in the absence of any microbicide. This basic information is needed just to construct the trials because, obviously, you can’t measure impact of a product unless you know what’s going on in the body in the first place.
These baseline studies are clinical trials because they involve human participants. But they are sometimes called “Phase 0” studies because no potential microbicides is used in them. They just measure the levels of injury and inflammation that typically occur in the rectum during anal intercourse.
This way, the researchers have a clear picture of what’s “normal” and they can then set parameters to measure product impact in future trials. The Phase 0 studies enable researchers to design effective Phase I safety trials for rectal microbicides

15. Laboratory research in action
Dr. Ian McGowan, HPTN 056
University of California/Los Angeles
Goal: To define measurements that can be made on rectal tissue biopsies that would be of use in rectal microbicide safety studies.
Repeated measurements on 16 men, and studied variation based on:
Time
Location in the rectum
Sero status
Here’s an example of a baseline research study that aimed to figure out what should be measured in rectal microbicides safety studies.
In 2005, Dr. Ian McGowan completed a study in Los Angeles looking at the physical changes that occurred in the rectal tissue of 16 men who were having anal intercourse. The volunteers agreed to undergo physical examinations and a number of tests to measure the changes that occurred in their bodies after intercourse – what trauma occurred, how quickly their tissues healed and how the body’s immune system responses to the impact of anal intercourse.
Dr. McGowan’s data contributes substantially to the development of a baseline picture of the regular “wear and tear” that anal intercourse causes in the body. Once researchers have a comprehensive picture of this baseline, they will be prepared to isolate the effects that may be caused by a candidate microbicide and correctly distinguish them from the normal post-intercourse changes that can be expected.
Dr. McGowan is now helping lead a the Microbicide Development Project which is a collaborative effort with two universities, the National Institutes of Health, the AIDS Research Alliance, and three biotech companies (Biosyn, Inc., Gilead Sciences, and Tibotec-Virco) . The project is focused on three candidate microbicides. The project is also split into three parts: first: looking at pre-clinical development using biopsies and animal studies; second: determining the most cost effective and predictive tests for use in future rectal microbicide development; and third, behavioral and acceptability issues. [More information is available at

16. Penile Acceptability Studies
To learn more about…
How much tissue is likely to be exposed to a microbicide
Impact of a product on the penis
As I mentioned before, distribution studies and studies to look at how candidate microbicides might affect the penis of the insertive partner are also underway. Each product being developed for vaginal use should be tested to see if it causes irritation to the rectum or penis. Obviously, if a product is irritating to the man’s penis, couples won’t want to use it even if it has been determined to be safe for internal use by the receptive partner.
So men are now being enrolled in penile acceptability or male tolerance studies. In these trials, volunteers are asked to apply the candidate microbicide to their penises before bedtime and then getting checked the next day to see if any negative side effects have occurred. These penile acceptability studies will also be done with any product that is determined to be a viable rectal microbicides, once such products are identified.

17. Distribution research in action:
Dr. Craig Hendrix at Johns Hopkins University in Baltimore
Volunteers simulated anal intercourse
MRI scans done up to five hours after its release
Initial studies suggest that semen could travel up to 60 centimeters
Showed where a microbicide would be needed to protect vulnerable tissues
Craig Hendrix of Johns Hopkins University in Baltimore conducted a study to look at how far an artificial semen substance and a “microbicide-like substitute” could travel up the colon during and after sex.
In this study, volunteers simulated sex with plastic dildoes and then received an ejaculation – made up of artificial semen and a lubricant the consistency of a microbicide. These substances were chemically labeled so that they could be viewed inside the body using an MRI scan machine. This way, the researchers were able to see how far the lube and semen would go.
These initial results suggest that four hours after sex, both the “semen” and “microbicide” may have traveled 60 centimeters (approximately two feet) up the colon, nearly to the spleen.
This study is causing researcher to think that rectal microbicides might need to be administered as douches or enemas in order to get high enough into the colon to work. Lubes, suppositories and gels may only work if they can disable HIV very quickly, before the semen has a chance to travel.

18. Behavioral Research To learn more about…
Prevalence of anal intercourse for both mean and women – and how many of these acts are protected
Preferences re: formulation and delivery systems
Sexual practices that affect microbicide feasibility
How much product is acceptable
Another category of study is behavioral research.
In these studies, researchers interview people to collect data on what they do and how they feel about things. This covers a whole ranges of topics including:
How prevalent is anal intercourse among men? Among women? Among youth? In various countries? In various sub-populations? How often to people use condoms versus have unprotected intercourse?
Clearly, we need to know more about this so we know who needs rectal microbicides.
It also included finding out more about
What people want in a rectal microbicide?
What will they find acceptable?
How much product ARE they willing to use and how much is “too much”?
How do people prefer to receive rectal microbicides – in the form of gels and creams? Suppositories? What would people actually use?
We also need to learn more about current sexual practices and their potential impact on microbicides. These practices may include douching, enemas, lubricant use, etc.

19. Behavioral research in action:
Alex Carballo-Diéguez, Columbia Univ (NY)
Ken Mayer, Fenway Community Health (Boston)
How much gel is tolerable?
18 HIV uninfected men
Maximum acceptable dose for insertion and anal intercourse
Exactly how much product gay men were prepared to tolerate was measured by Dr. Alex Carballo-Diéguez, a researcher from Columbia University in New York, and Ken Mayer’s team at Fenway Community Health in Boston.
They enrolled 18 HIV-negative men of diverse ethnic backgrounds – each of whom had a history of engaging in receptive anal intercourse with HIV positive men or men whose serostatus they did not know. They recruited these men thought the Fenway Community Health Center in Boston, the largest gay health center in New England.
The participants agreed to self-administer increasing volumes (5 ml, 20 ml, 35 ml, and then 50 ml) of a microbicide-like gel (with no active ingredient) on different days -- and then rate the volume acceptability. This means they wrote down how the product felt and whether they thought they could use that much product comfortably. Once each individual reached the maximum volume acceptable to him, he was asked to have receptive intercourse while using that volume of gel and while his partner was using a condom. Then he rates how he felt about the volume of gel during sex.
After having intercourse with the gel on three separate occasions, each participant went through an in-depth interview with a researcher and everything he said about his experiences with the gel (on its own and during sex) was captured and analysed.
What they found was very interesting. Two participants dropped out but half of the remaining participants said they were comfortable with 50 ml of the gel (the highest volume they were asked to use). The study isn’t completed yet but it will be very interesting to see how the other half of the participants felt about using the gel during sex and how much was too much.
You can easily see how this kind of research is very important to the development of a rectal microbicide that people will really want to use.

20. Behavioral research in action:
Alex Carballo-Diéguez and Sigma Research Center both did surveys of MSM interest in using microbicide
Results:
In San Francisco: 59% heard of microbicides, 25% - 35% might use (depending on stated effectiveness)
In the UK: 23% had heard of microbicides, 59% might use
Sometimes broader behavioral data is collected more quickly and from larger numbers of participants by using surveys.
Dr. Carballo-Diéguez did one such survey in San Francisco between May 2002 to January His research team surveyed 879 adult men who have sex with men during that time.
Of these, 59% said they had heard of microbicides but their willingness to use them depended heavily on how effective the microbicide would be. When told that a microbicide might not be as effective as condoms, only 25-35% of the respondents said they would be interested in using them. These findings suggest that it might be important to emphasize that a rectal microbicide could be used with condoms as additional safety and to make sex more pleasurable – as well as a way of reducing risk if condoms are not being used.
Another survey done in the UK showed a high rate of interest but did not follow up with questions about potential effectiveness. In 2003, Sigma Research did an extraordinary internet survey of more than 10,000 men who have sex with men in the UK. Only 23% of those respondents had heard of microbicides. But once the concept was explained, 59% said they would consider using a rectal microbicide if one were available.

21. More vital steps
Men and women need education about the risks of unprotected anal sex
Safety trials on rectal application of vaginal microbicides that are currently in large scale trials
Testing over the counter lubes to see how safe they are
Advocacy for increased research
In addition to the baseline, distribution, irritation and behavioral research into rectal microbicides that I have just described, more work remains.
As we saw earlier, millions of people are having unprotected anal sex. Both men and women need to know about the risks of unprotected anal sex as a route for HIV transmission.
In addition, there are several tasks more specific to microbicides that we need to undertake now in order to move the field forward as rapidly as possible: we need to ensure that candidate vaginal microbicides and currently available over the counter lubes are safe for rectal use. We also need to advocate for sufficient funding for microbicide research.

22. Rectal safety trials on vaginal products
We won’t know if the first vaginal microbicides are effective for rectal use
But we must know if they are safe to put in the rectum or not
Because some people will try to use them rectally
If deemed harmful for the rectum, labels warning against rectal use are imperative.
Although we won’t know the effectiveness of vaginal microbicides for anal intercourse, we do have the ability to test their safety now – before anything goes on the market for vaginal use.
We know from experience that --as soon as a product is marketed for vaginal use -- some people will use it rectally if they think it could give them even limited protection.
So even products designed for vaginal use must be tested rectally to find out if they are likely to be harmful when used in the rectum. Until we know for sure about rectal safety, it will be important for vaginal products to be issued with warning labels cautioning people not to use them rectally.
We also need to know the safety profile of the sexual lubricants that are sold over the counter (without a prescription) when they go into the rectum. People use sexual lubricants for anal sex all the time and using a lube can increase safety by minimizing the amount of tearing and trauma to rectal tissue that occurs during intercourse.
But is it possible that some lubricants are more irritating than others. Are they causing irritation that may increase the user’s vulnerability to HIV? If so, we need to know!

23. Testing on over the counter lubes
Drs. Sudol & Phillips at Population Council, New York
Tested 5 OTC lubes in mice to see if they caused damage to rectal cells
KY-Plus (no longer on market) and DeLube caused the most damage
Viamore, Vagisil and Astroglide caused some damage
More research is underway, with findings expected soon.
Need more research to see if these products cause damage to human rectal cells
In 2004, the Population Council published a study describing the impact of several over-the-counter lubricants on rectal epithelia. Using a mouse model, they tested the degree to which internal application of various products caused cells in the rectal lining to slough (peel) off, leaving the rectum more vulnerable to infection.
They found that DeLUBE and KY-Plus were most likely to cause damage to the rectal lining. Viamore, Vagisil and Astroglide were relatively less cytotoxic (capable of killing cells) but, nevertheless, caused a significant degree of rectal damage. They noted that, “the only products that do not exhibit any cytotoxicity are Carraguard and methylcellulose, which are not yet commercially available.”
Research is on-going with the (currently unpublished) findings suggesting that some of these products are cytoxic and cause significant rectal sloughing.
As advocates, we need to help publicize these recent findings, especially with regard to the risk potentially associated with DeLUBE (manufactured by E-Gal Corporation). We also need to demand that more studies are done on OTC lubricants, to confirm or challenge these findings.
We must tell our communities that these products have only been approved their sale as sexual lubricants -- products designed to be applied in very small amounts externally (on the vulva or penis), not internally by applicator. These findings also underscore the need for rectal safety trials in humans of existing and future sexual lubricants and microbicides. Since lubricants are an important tool for reducing the risk of rectal tearing and condom breakage, it would be extremely helpful to know which lubricants pose the least risk of rectal cytotoxicity.
[Kristen Sudol and David Phillips, Sexually Transmitted Disease. June 2004 (pages )]

24. Advocacy for rectal microbicides
Microbicide research is drastically under-funded
Need for increased funding for both vaginal and rectal microbicides
Talk to your government officials
e.g., U.S. Microbicide Development Act
A final vital step is to ensure that rectal microbicides are a reality in our lifetime, we need to “make some noise”.
Microbicide research – whether vaginal or rectal – is drastically under funded. The large pharmaceutical companies that usually fund new drug development have shied away from microbicide research because they see it as too much financial risk for too little profit. As a result, the task of microbicide development has fallen to scientists at nonprofit organizations, universities and small biotech companies – all of which rely on government grants and foundation contributions to keep their research going. Progress has been slow, however, due to inadequate funding.
In addition to the scientific challenges that make rectal microbicides more difficult to develop than vaginal microbicides, homophobia and stigma have further slowed down the progress of necessary research on the prevention of rectal infections. In the U.S., getting investment in rectal microbicides is even harder because people are hesitant to talk about anal intercourse. Groups in the U.S. have had to drop the word “rectal” dropped from abstracts and grant submissions in order to receive funding.
The escalating numbers of new HIV and STI infections resulting from unprotected anal intercourse testify to the fact that having one prevention tool, condoms, just isn't enough. It is time for receptive partners to have methods they can control. It's time for rectal microbicides. In the face of these challenges, we must advocate even louder for research into microbicides – both vaginal and rectal. Support for legislation like the U.S. Microbicide Development Act (MDA) would authorize increased funding for essential research. (More information at campaign.org/legislativeadvocacy.htm)
Before we leave here, I want to tell you about three different initiatives that are underway to support microbicides in general. Two of them support rectal microbicides in particular. These are the Global Campaign for Microbicides, Lifelube.org and the International Rectal Microbicides Working Group.

25. Global Campaign for Microbicides
A worldwide effort co-sponsored by groups working on
HIV/AIDS
reproductive health
gay health
women’s empowerment
Working to educate, raise awareness and generate collective advocacy for increased political and public investment in microbicide development
The Global Campaign for Microbicides is a broad-based, international effort to build support among policymakers, opinion leaders, and the general public for increased investment into microbicides and other user-controlled prevention methods. With over 250 endorsers worldwide, the Global Campaign is organizing through community and constituency groups at all levels -- from national and international NGOs to grassroots organizations, churches, community centers, sororities and clubs.
People can’t demand what they have yet to envision. So the Global Campaign works to educate people, through presentations like this one, about the fact that microbicides – both rectal and vaginal - are possible. Then we have to get people talking to their legislators and policy makers -- in their own ways and their own countries -- about the urgent need for such methods.

26. New strategy to raise awareness and demand among gay men
LifeLube.org
New strategy to raise awareness and demand among gay men
Three components:
Internet –
Public presence in forums & conferences
Media – print, electronic, guerilla!
Despite the fact that rectal microbicides may offer an acceptable risk reduction alternative, little has been heard about microbicides in the gay press or among gay men’s health promoters.
Gay men’s voices were at the forefront of successful activist pressure for new HIV drugs a decade ago and are prominent now in the “global access to treatment” advocacy that is changing pharmaceutical pricing and distribution policies. Men engaged in these advocacy fronts constitute a natural, although previously untapped, constituency for microbicide advocacy.
The Global Campaign for Microbicides is working with the AIDS Foundation of Chicago as they develop a new initiative to engage this constituency. Lifelube.org will use a range of techniques including promotion of the topic in the gay-focused media, visibility at treatment advocacy and gay men’s health conferences, and outreach via a website designed to present information on microbicide research and development in the context of gay men’s needs and interests. Questions that they are asking include:
How do we encourage gay men to get involved in microbicide advocacy?
How do we build, sustain energy and excitement without overselling, or burning out?
What do we begin educating our communities about microbicides?
How do we make sure our concerns, values and behaviors are taken into consideration in every phase of the R&D process?

27. International Rectal Microbicides Working Group
Working Collaboratively:
Global listserv
Bi-monthly conference calls
Developed an advocacy agenda
To join, contact Jim Pickett,
Presence at conferences:
Microbicides 2006 conference
Gay Men’s Health Conferences
Gay and Lesbian Medical Association annual meeting
In 2005, almost simultaneously, microbicides, HIV/AIDS, gay men's health and sexual and reproductive health advocates across the globe mobilized to form several Rectal Microbicides Working Groups. Today, after merging together, the International Rectal Microbicides Working Group has nearly 200 members in 24 countries on 5 continents.
In April 2006 at the Microbicides 2006 conference in Cape Town, the IRMWG released an important document titled "Rectal Microbicides: Investments and Advocacy." This document is the first-ever analysis of the resources allocated specifically for the research and development of rectal microbicides. The group found that between 2000 and 2006, $34 million was spent on rectal microbicide R&D, most of that from the US public sector. The group recommends a minimum of $350 million for target rectal microbicide research fudning over the next years, or an average of at least $35 million per year to build a comprehensive rectal microbicide research program. The full document is available for dowload at
This dynamic group has been working to coordinate advocacy efforts, shape and expand the LifeLube project, and share timely information around the advancement of rectal microbicides. Regular conference calls feature presentations from researchers and policy experts.
If you are interested in joining, you can Jim Pickett at the AIDS Foundation of Chicago,

28. What you can do Visit www.global-campaign.org or www.lifelube.org to
Join the International Rectal Microbicide Working Group calls and listserve
Learn more about rectal microbicides
Sign up for the Global Campaign’s newsletter
Host a talk on microbicides – this and other presentations available for download
Endorse the Global Campaign
I don’t want you to leave here today thinking that you, as an individual can’t make much of a difference on this issue. You can.
You can join the International Rectal Microbicide Working Group to participate in monthly conference calls or receive emali updates
You can visit these two websites to learn more about microbicides after this talk.
You can sign up to receive the Global Campaign’s monthly e-newsletter
At these websites, you can also download a basic rectal microbicides presentation like this one, as well as others.
You can urge community groups, organizations and service providers in your community to host a free program on microbicides. We’ll be glad to work with you on organizing those programs and finding presenters for you.
In the end, we need your voices to ensure that rectal microbicides receive necessary funding and attention so that we can have another tool to protect both men and women in the next decade.
I would love to hear what you think and answer any of your questions now.