1. Microbicides: New Hope for Prevention of HIV and other STIs
[Please start off by introducing yourself and your organisation. Say why you are making this presentation and why this issue is important to you. You may want to say that you are doing this presentation on behalf of the Global Campaign for Microbicides which is a coalition of 300 non-profit organisations that advocate for new HIV prevention options. The Global Campaign does not sponsor trials or do the research. Then you could say something like:]
Microbicides are products that have the potential to transform the HIV prevention landscape by giving us a new method of protection that is user-initiated, instead of partner initiated.
I think it is clear to all of us that not everyone has the power in their relationships to insist on condom use during every act of intercourse. So we need to start talking about what IS possible for women and men in this situation -- what can be developed that would enable both partners to protect themselves when a condom isn’t being used and add to the effectiveness when condoms are used.
Today, I would like to talk about three things:
1) First, I will introduce you to the concept of microbicides and how they might fit into an overall program of HIV prevention;
2) Then, I will talk a little bit about how microbicides are being developed, how they would work and where the research is at right now;
Finally, I will talk about why we have to develop a vocal and active constituency for microbicides to make sure that this vital new technology reaches the market as soon as possible.
[Note to speaker: References are on the final page of the script for this presentation; You are welcome to add your group’s logo to the home page, and your website to the bottom of each slide]
Date of last update: February 2008
Your name here

2. What is a Microbicide?
A substance that can reduce the transmission of HIV and other STI pathogens when applied vaginally and, possibly, rectally. They are not yet available.
Early products:
Gels and creams
In the future:
Sponges, vaginal rings
Gels with barrier devices
So what is a microbicide? A microbicide is any substance that can substantially reduce the risk of acquiring or transmitting sexually transmitted infections, including HIV, when it is applied in the vagina or rectum.
It’s important to understand that no proven microbicides exist yet on the market. What we’re talking about here are products that are still being researched.
The earliest that a microbicide could be available is in the next 5 years. Even then, this will be in a handful of countries most impacted by HIV/AIDS. These early products will probably look a lot like the over-the-counter yeast infection treatments and birth control products we already know -- the gel, foam, cream and suppository-type products that have been on the shelves for years. They won’t contain the same chemicals as these birth control products but they will come in some of the same formulations.
But scientists are also working on developing new formulations that may eventually make microbicides even more user-friendly than today’s spermicides.
For example, they’re working to make formulations that women can use several hours or even days before intercourse, if necessary. One possibility is a vaginal ring or sponge-- something that could slowly release the protective substance over time, providing round the clock protection. Another possibility is combining a physical barrier -- such as a diaphragm or cervical cap -- with a microbicide. Since the cervix is more vulnerable to infection than the vaginal walls, this combination might provide highly effective protection.
© Salam Dahbor, Courtesy Doubleshots Studio

3. We Need a Range of Products
Contraceptive and non-contraceptive
Reduce risk of other STIs
Safe and non-irritating
Inexpensive and available over the counter
Could be used without partner’s cooperation or even awareness
Some of the microbicides being developed will also be contraceptive. And that’s great because many women would like to have a product that can protect them from disease and pregnancy at the same time. But scientists are also working on non-contraceptive microbicides that would be helpful to women and men who want to conceive a child while still protecting themselves from possible infection --- something that is impossible with condoms.
Some microbicides are also being tested for efficacy against other sexually transmitted infections (STIs), and several of them appear to reduce risk of at least one or two other STIs. Eventually, scientists may be able to combine active ingredients so that one product can serve several purposes.
Obviously, we need products that are safe and don’t irritate any tissue or organs. 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.
The issue of access is one of the fundamental goals of the Global Campaign. Advocates around the world are already working to make sure that microbicides are affordable and easily accessible and made available without a prescription.
Finally, when using a microbicide, a woman wouldn’t need to gain her partner’s active cooperation at each act of intercourse – the way she has to with male or female condoms. Many women probably will choose to discuss microbicide use with their partners. But this could be a one time conversation -- and it wouldn’t have to happen right before sex. After that, the woman could manage her own protection without need to “negotiate” or interrupt sexual spontaneity every time.

4. Expected Protection Regulators will look for 40-60% protectiveness
Promoted as a back-up to condoms, not as a replacement.
“Use a microbicide with your condom for added pleasure and protection.”
“Use a male or female condom every time you have sex; if you absolutely can’t use a condom, use a microbicide.”
Microbicides will help people reduce risk of infection -- but we need to be clear about the fact that they aren’t going to eliminate risk.
Microbicides will probably never be as effective as condoms.7 It’s safer to keep a virus out of your body than it is to try to kill or disable it once it’s there. That’s common sense.
But remember, we’re talking about microbicides as an option for people who can’t or don’t use condoms.
Scientists do not know exactly how effective microbicides will be. But it is likely that to be approved by drug regulators and accepted by policymakers and users, microbicides would have to reduce risk of HIV by at least 40 to 50%.
Later microbicides are likely to be more effective as researchers accumulate knowledge and learn how to make them work better. But even a partially effective microbicide could be valuable in terms of helping people protect themselves.7
A condom with 80 to 95% effectiveness8 is definitely the most effective disease prevention option, but it has ZERO effectiveness if a couple is not using it. It is our hope that although microbicides may be less effective, couples may be able to use them more consistently than they currently use condoms.
So we should talk about microbicides as part of a risk reduction approach. We need to encourage people to continue to use condoms if they possibly can. Many folks may want to use microbicides with their condoms for back-up protection and added pleasure.
Microbicides would give us something to suggest when a woman says “I just can’t make him use a condom. Isn’t there something else I can do to protect myself?” Once microbicides become available, we’ll be able to answer by explaining clearly that these new products aren’t as effective as condoms -- but they are much better than nothing. And, as we all know, a lot of women are getting infected because “nothing” is all they have.

5. Comprehensive Strategies for Protection
Social Power
Protection
None of these new technological interventions – vaccines, microbicides, condoms, or PREP, will be a magic bullet to combat the HIV/AIDS pandemic.
Technology is just one piece of a comprehensive response. In order for women to really be able to use these technologies, we need to address the broader structural issues that make it difficult for women to insist on condoms in the first place. We need to work to give women more economic opportunities and more social power. This means everything from:
Reducing violence against women
Protecting the property and inheritance rights of women and girls
Supporting on-going efforts toward universal education for girls
Economic Opportunities
Technology
Source: Brady, Martha. Population Council, Conceptual Framework

6. Potential Public Health Impact
If a 60% effective product
Offered to 73 lower income countries
Is used by 20% people reached by health care
during 50% of unprotected sex acts
= 2.5 million HIV infections averted
in 3 years including women, men and children
Even if we are talking about partially effective microbicides that complement other interventions, they could still have a big impact. Computer modelling conducted at the London School of Hygiene and Tropical Medicine estimates that:7
if a 60% effective microbicide
is introduced in 73 low income countries with high HIV rates
and gets used by only 20% of the people with access to existing health services
and those people use it only half of the time when they’re not using condoms
over 3 years it could prevent 2.5 million new HIV infections among women, men & children.4
I’m not saying that this impact would be immediate. But we’re still talking about millions of lives potentially saved. And, as you see, these calculations are on relatively modest estimates of effectiveness, uptake and use. A more effective microbicide, used by a larger number of people, would have an even greater effect.
Microbicides are not a panacea. But they could save a lot of lives and make an enormous difference in the spread of the pandemic.
Now before I tell you more bout how microbicides work and where we are at in the research, are there any questions before we move on?

7. 1. boosts vagina’s natural defenses 2. surfactants
So how do microbicides work?
The products now in the research pipeline fall into four basic categories -- defined by how they work. These are also known as ”mechanisms of action”. This slide is a picture of the vaginal wall and illustrates the different ways that candidate products might work to reduce infection.12
1. The first approach is to build or improve upon what the body already does to protect itself. For example a healthy vagina is normally acidic, which makes it inhospitable to invading pathogens like HIV. But semen counteracts this acidity, creating an environment where HIV can survive. Some candidate microbicides build on the simple principle of maintaining the vagina’s natural acidic even in the presence of semen.
2. Surfactants disable the virus by breaking up its surface membrane or envelope. They can also disable sperm in the same way so they are also effective contraceptives. The trick is to make sure that surfactants are strong enough to disrupt the invading pathogen, but without damaging the healthy cells that line the vagina’s walls.
3. Entry inhibitors work by interfering with the virus getting into the body’s white blood cells—the target cells of HIV. There are two categories of entry inhibitors: attachment inhibitors that prevent attachment of the virus to the white blood cell and fusion inhibitors that prevent HIV from actually entering the cell.
4. Finally, some microbicides are being created by reformulating the same anti-retroviral drugs developed to treat people with HIV. These drugs are designed to stop HIV from replicating. So what happens if you make them into products that can be applied in the vagina? Could you stop the replication of any HIV that enters a vaginal cell so that the virus does not have a chance to disseminate and enter the blood stream? That’s what some researchers are trying to find out.
The first microbicides to become available may operate with just one mechanism of action. It is very likely, however, that later microbicides will be combination products -- using two or more mechanisms of action to enhance their effectiveness.
4. anti-retrovirals
3. entry inhibitors
Source: Shattock, R.; Moore, J. Inhibiting Sexual Transmission of HIV-1 Infection. Nature Reviews Microbiology. Vol 1, October 2003.

8. The Product Pipeline in 2008
3 products
3 products
6 products
30+ products
Laboratory Testing
2-6 Years
Phase I
(safety)
1 to 6 Months
Phase II
(safety)
Up to 2 Years
Phase III
(efficacy)
2 to 4 Years
25 – 40 people
people
3,000-10,000 people
As you can see, drug development is a long and complicated process…taking more than a decade to develop and test a new drug for use.
Before any new drug candidate can be tested in human beings, the developers have to show that (a) it’s not likely to be harmful to humans and (b) it may be beneficial. The research is done in laboratory testing and in animals and can take anywhere from 2 to 6 years. Currently there are over 30 candidates in pre-clinical testing (i.e. that is, that have not yet entered human testing).
If a product is approved for human trials, it goes first through a series of Phase I safety trials, where small numbers of people who are at low risk of infection use the product and are carefully monitored for signs of problems. Next come one or more Phase II trials to gather extended safety data and establish safety among different groups of people–-for example, those who may already be HIV positive or have another sexually transmitted infection.
If a product is shown to be safe in these first two phases, a product can then be tested for effectiveness. The Phase III trials can take several years because they need to enroll thousands of women who use the product for many months up to several years to see if it reduces their risk of HIV infection. It may be necessary to do two Phase III trials before a product can be licensed for use. Sometimes Phase 2 studies are expanded to become Phase 2b trials, which are similar to Phase 3 trials in scope. We have therefore included these in the Phase 3 column here.
While clinical trials are going on in women, researchers also need to undertake separate trials to look at whether the product is irritating to the penis or rectum.
[Products in Phase I/II are counted as Phase II and products from Phase II/IIB are counted as Phase III products. 13]
Simultaneous studies in some cases:
HIV+, penile & rectal safety
10 or more years
Source: Alliance Pipeline Update, first week of every month -

9. When can we expect a microbicide?
Next Phase III trial results expected in 2009
Earliest possible access in a few countries via introductory studies within the next 5 years
If not, we will have to wait for results from candidates now in Phase II trials
Results from the trials now furthest along could become available in 2009, but it will take additional time for the products to be reviewed and approved for licensure – at least 1-2 years. Thus, a microbicide could be ready for introduction in the next five years, but that would only happen in a few countries, and most likely through smaller scale introductory programmes.
If the current set of products in effectiveness trials does not prove effective, the time horizon will be longer. There are several second-generation leads already in human testing, so we need to ensure that the entire pipeline continues to advance.
Due to advocates work around the world over many years, millions of people have heard about microbicides. The challenge that the microbicide field faces now is to find the correct balance between building enthusiasm and political support for microbicides, while avoiding raising unrealistic expectations in the media or our outreach work.

10. Public Funding is Essential
Why aren’t large pharmaceutical companies investing?
Perceived low profitability
Liability concerns
Lack of in-house expertise
Uncertain regulatory environment
Philanthropic Sector, 12%
Public Sector, 86%
New drugs are usually developed by large pharmaceutical companies with the resources to pay for large clinical trials and other costly research processes. Microbicides-- like malaria vaccines, new contraceptives, and many other products – however are called “public health goods”. They could yield huge returns to society but they hold little profit potential for private investors. Thus, no large pharmaceutical companies are putting substantial funding into microbicide research yet. Instead, small biotech companies, universities, government agencies, and non-profit entities are doing the research and are being funded by governments and private foundations.17 This means trials are not moving forward as rapidly as they could because they are delayed due to lack of money.
Some large pharmaceuticals have allowed non-profit groups to test products that they own. The pharmaceutical companies do not pay for the trials for these products, they simply lend the product to these non-profit organisations. It is still tax payers and private foundations that are footing the bill for these very expensive clinical trials – up to $50 Million for a Phase III trial18. Money remains a major limiting factor in how rapidly microbicide research can proceed. In fact, we need the annual funding levels to double if we are to reach our goal.
For a full analysis of the funding going into the field, we recommend the new report from the HIV resource tracking group, available at hivresourcetracking.org 19.

11. The Global Campaign for Microbicides works to:
Ensure that as science proceeds, the public interest is protected - Accountability
Mobilise demand and investment for research and development of new prevention technologies
Conduct policy advocacy for development, introduction, access, and use
The Global Campaign for Microbicides was created to coordinate and support advocacy in the microbicide field toward three goals.
First, a cornerstone of our work is to ensure that, as the science proceeds, the public interest is protected and the rights and interests of trial participants, users, and communities are fully represented and respected. The Campaign works with partners in trial communities to make sure that they are fully informed and involved in how the trials proceed. We want to make sure that the researchers are accountable to the communities they work with.
Second, the Campaign works to mobilise resources that will accelerate the process of microbicide research and development. But people can’t demand what they have yet to envision. So we start by raising awareness so that the people see microbicides as a possible tool that they have the right to demand.
Finally, the Campaign advocates for timely and fair development, introduction, and use. We are vitally concerned about access -- making sure that the approved products will be widely available and introduced in a way that helps people understand them and use them correctly. This means we also have to focus on issues of pricing, distribution, stigma, gender bias and women’s empowerment, as well as product development and approval.

12. What You Can Do Visit www.global-campaign.org…
Get in touch with local advocates
Sign up for GC News
Write to your public officials!
Endorse the Global Campaign
Educate others:
Presentations
Events
Web-links
I don’t want you to leave here today thinking that you, as an individual, can’t make a difference on this issue. You can.
The first thing you can do is link up with a Global Campaign partner organisation if there is one active in your area. They will welcome your involvement -- even if you just want to be on their mailing list to find out more about what’s going on locally.
At our website, you can sign up to receive the Campaign’s (free) monthly e- newsletter, find additional information about what’s happening in the microbicides field, and also write to your public officials.
You can urge community groups, organisations and service providers in your community to endorse the Global Campaign.
Finally, now that you have heard this presentation, you know more about microbicides than most people around the world. We hope that you will join us in spreading the word about this vital new technology. You can make a presentation like this one – the slides and accompanying script are on the Global Campaign website, you can write an article on microbicides in a newsletter, or you can distribute the Campaign’s simple factsheets, available in a variety of languages. Finally, you can order the short film, In Women’s Hands and incorporate it into an event. Please come talk to me after the presentation to talk about how you can get involved.
I want to leave you with an image that I find inspiring – it is a picture of five women who worked at a clinical trial site in Uganda. Thank you for your attention.
Newsletters
Use the short film
Fact sheets

13. References: I don’t want to die before I turn 25.
Remember! Updates of this presentation are available at
1. World Health Organization, AIDS Epidemic Update. December 2007.
2. World Health Organization, AIDS Epidemic Update. December 2007.
World Health Organization, AIDS Epidemic Update. December 2005.
3. European Study Group on Heterosexual Transmission of HIV. Comparison of female to male and male to female transmission of HIV in 563 stable couples. British Medical Journal ; 304:
4. Economic Security for Women Fights AIDS. Global Coalition on Women and AIDS Report, Issue #3. UNAIDS Initiative. Geneva, Switzerland
Kelley Hallman, “Gendered socioeconomic conditions and HIV risk behaviors among young people in South Africa,” African Journal of AIDS Research, 2005, 4(1):37-50.
Richard Strickland, “To Have and To Hold: Women’s Property and Inheritance Rights in the Context of HIV/AIDS in Sub-Saharan Africa,” ICRW Working Paper, June 2004.
5. Garcia-Moreno C and Watts C (2000) ‘Violence against women: its importance for HIV/AIDS’, in AIDS, 14, Geneva.
6. Royce, R.A.; Sena, A.; Cates, W. Sexual transmission of HIV. New England Journal of Medicine. 1997; 336:
Abreu, M.; Anton, P.; Coombs, R. Anatomy, physiology, immunology of the anorectal mucosa. From: Rectal Microbicides Workshop: Baltimore, MD, June 7-8, 2001; Rectal microbicides that protect against HIV infection:8. American Foundation for AIDS Research.
7. Foss, A.; Vickerman, P.; Heise, L. Shifts in condom use following microbicide introduction: should we be concerned? AIDS 2003, 17:
8. Studies show that consistent use of latex condoms reduces the likelihood of HIV infection by 80 to 90 percent. “USAID: HIV/STI Prevention and Condoms. May 2005”: 
Pinkerton, S.D.; Abramson, P.R. Effectiveness of condoms in preventing HIV transmission. Social Sciences & Medicine 44(9):1, From Condom Promotion for AIDS Prevention in the Developing World: Is it Working? By Norman Hearst and Sanny Chen.
Davis KR and Weller SC. The effectiveness of condoms in reducing heterosexual transmission of HIV. Fam Plann Perspect 1999;31:
Weller S, Davis K. Condom effectiveness in reducing heterosexual HIV transmission (Cochrane Review). In: The Cochrane Library, Issue 2, Chichester, UK, John Wiley & Sons, Ltd.
HIV Tools Research Group: Department of Public Health and Policy, London School of Hygiene and Tropical Medicine. Are people using condoms? Current evidence from Sub-Saharan Africa and Asia and the implications for microbicides. November available from GCM website:
10. Foss, A.; Watts, C. Condoms and prevention of HIV are essential and effective, but additional methods are also needed. British Medical Journal. Vol July pp
Jenkins, R. A.; Manopaiboon, C.; Samuel, A. P. Condom use among vocational school students in Chiang Rai, Thailand. AIDS Educ Prev 2002; 14(3):
11. Brady, Martha. Population Council, Conceptual Framework
12. Shattock, R.; Moore, J. Inhibiting Sexual Transmission of HIV-1 Infection. Nature Reviews Microbiology. Vol 1, October 2003.
13. Alliance for Microbicide Development. February 2008 Pipeline Update.
14. Alliance for Microbicide Development, Microbicides Research and Development Database.
15. Microbicide Clinical Trials: Needs and Challenges, Salim Abdool Karim, MBChB, PhD, Director, Centre for the AIDS Programme of Research in South Africa (CAPRISA), Presented at US Congressional briefing, 18 July 2006.
16. Building a comprehensive response: Funding for HIV vaccines, microbicides and other new prevention options: UNAIDS,
17. Quote from last slide: Quote found in UNICEF, Facing the Future Together: Report of the Secretary-General's Task Force on Women, Girls and HIV/AIDS in Southern Africa, July – Quote from UNICEF’s Voices of Youth,
Frank Herholdt, Courtesy of Microbicide Development Project
I don’t want to die before I turn 25.
I refuse to sit down and watch my generation fall to pieces.
I am going to make a difference…Will you?
Rumbidzai Grace Mushangi, age 15, Zimbabwe