Topical Microbicides: New Hope for Non-Condom Prevention of HIV and other STDs

1. Topical Microbicides:New Hope for Non-Condom Prevention of HIV and other STDs Your name here on behalf of the Global Campaign for Microbicides www.global-campaign.org

2. The Global Challenge • AIDS kills more people than any other infectious disease • in Botswana, 36% of all adults are infected. • in Sub-Saharan Africa, 67% of the almost 9 million HIV youth (15-25 years) are female • HIV is rapidly becoming a “women’s epidemic” • of every 10 people newly infected with HIV, 6 are women • even in the developed world, rates of new infections among women are rising

3. What is a microbicide? Microbicides are substances that can reduce the transmission of HIV and other STD pathogens when applied vaginally and, possibly, rectally. Currently,they are topical products formulated as gels or creams applied with an applicator. Future formulationscould include sponges, time-released vaginal rings or gels combined with barrier devices such as diaphragms or cervical caps.

4. What would they be like? • Some will also prevent pregnancy • Others will be microbicidal but not contraceptive • Many candidate products are broad spectrum reducing risk of some other STDs, in addition to HIV

5. Other advantages... • Will be available over the counter • could be distributed like condoms in stores, at agencies or by outreach workers • Are likely to be inexpensive • Could be used without the partner’s cooperation or even awareness • Some will help boost the vagina’s natural defenses

6. How would we use a microbicide? • Along with condoms for extra protection • As primary protection for individuals and/or couples unable or unwilling to use condoms consistently • As a mouth rinse for protection during oral sex. • As a potentially low-cost way of reducing perinatal transmission via vaginal washing prior to delivery

7. How would they benefit HIV+ women? • Reduce risk of re-infection with other HIV strains • Help protect their partners -- that is, bi-directional effect • Reduce risk of other STDs, yeast and bladder infections • Increase chances of getting pregnant safely and having HIV negative babies

8. Microbicides & anal sex • The biological challenge of creating an effective rectal microbicide is more complicated • Many people (women and men) need microbicides for anal sex • We must ensure that vaginal microbicides are accurately labeled – because some people will think of trying to use them that way

9. How effective will they be? • First microbicides will be 40-60% protective • Second generation products will be 60-80% • should be promoted as an adjunct or “back-up” to condoms, not as a replacement • use with harm reduction messages, such as: • Use a male or female condom every time you have sex; if you absolutely can’t use a condom, use a microbicide • Use a microbicide with your condom for added pleasure and protection

10. Prior to exposure Point of transmission Treatment Positioning microbicides in the prevention spectrum Prevention • Behavior change • Vaccines • Pre-exposure prophylaxis (PREP) • Male and female condoms • Anti-retroviral therapies • (mother-to-child) • Microbicides • Anti-retroviral therapies • Opportunistic infection therapies • Basic care/nutrition Microbicides offer a woman-controlled method to reduce transmission.

11. Why non-condom prevention? • Existing methods -- condoms and mutual monogamy -- depend upon the cooperation of a male partner. • Violence, coercion, and economic dependency in relationships make it hard to “negotiate” condom use or to leave a partnership that puts a woman at risk.

12. Women of reproductive age in Sub-Saharan Africa who reported condom use in last sex act

13. Condom use with regular partner post intervention

14. What about “condom migration”? • Will individuals switch from using from condoms to microbicides because they are easier to use? • Three lines of evidence suggest that introducing microbicides will lead to more protection rather than less • experience from family planning • research data • insights from modeling

15. Experience from family planning • Addition of each new method increases overall number of protected acts and decreases unintended pregnancies. • Adding a new contraceptive method to those available in an existing program increases overall use by about 12 percentage points, and decreases crude birth rate by 5.3 points. (Ross,J & E. Frankenberg.1993 Findings from Two Decades of Family Planning Research. Population Council)

16. Existing condom use research • 9 existing studies – Two designs: • 1) condom only compared to condom plus gel or • 2) condom only compared to hierarchy of prevention options (including female condom and gel); • all but one focus on STD clients or sex workers • 6 found that availability of additional protection options resulted in overall increase in consistent condom use • 3 found some evidence of migration • 3 highlight that consistent microbicide use could be achieved by women who could not use condoms

17. Mathematical modeling suggests…. • Under most circumstances, probable levels of condom migration do not increase risk of HIV transmission • of individuals • of sub-populations • Condom migration is potentially a problem only where condom use is high (> 70%) AND achieved microbicide consistency is low (< 50 % of sex acts where condom isn’t used) (Foss et al, Shifts in condom use following microbicide introduction: should we be concerned?. AIDS 2003, 17:1227-1237)

18. Tipping Point: When Does Condom Migration Affect Risk? IF 50% efficacious microbicide used in 50% of acts not protected by condoms Condom Consistency BEFORE Microbicide 30% 50% 70% 90% Condom Consistency AFTER Microbicide 5% 32% 59% 86%

19. Tipping Point: When Does Condom Migration Affect Risk? IF 50% efficacious microbicide used in 100% of acts not protected by condoms Condom Consistency BEFORE Microbicide 30% 50% 70% 90% Condom Consistency AFTER Microbicide 0% 0% 37% 79%

20. Will Women Use Microbicides? • In US study, an estimates 21.3 million women interested in using a microbicide (Darroch & Frost, 1999) • Even in resource-poor countries, women at risk are willing to pay twice as much (or more) than the local price of a condom (EU study, 1998; Hardy, et al 1998) • Women have widely different needs and formulation preferences so multiple products will be the key to widespread acceptability and use

21. How microbicides are developed • Kill or inactivate the pathogen • disrupt the surface membrane • create an inhospitable environment for the pathogen • Create a barrier between pathogen and vulnerable tissue • Coat mucous membranes with gel

22. Mechanisms of Action • Interfere with fusion of virus to target cell

23. Mechanisms of Action • Prevent replication once virus has entered the cell • Anti-retrovirals applied topically • Boost vagina’s natural defenses • Defensins, antibodies • Combination approach

24. What about Nonoxynol-9? • Tested in the 1980s and 90s to see if existing products might prove effective against HIV • Previous studies in humans had suggested that it gave some protection against gonorrhea, chlamydia and HIV • In July, 2000, study results showed that sex workers using low-dose product had higher rates of HIV sero-conversion than those using placebo -- possibly due to increased vaginal disruption caused by the N-9

25. World Health Organization says • N-9 does not provide protection against HIV or bacterial STDs like gonorrhea and chlamydia. • In vagina -- frequent use (more than once daily) can cause epithelial disruption, possibly increasing HIV risk • N-9 products should never be used rectally, even on condoms or lubes. The rectum is fragile and can be damaged by N-9 • Women at risk of HIV or who have intercourse more than once daily shouldn’t use N-9 spermi-cides. But they are still a safe contraceptive option for women who are not at risk of HIV.

26. Clinical research process In vitro (Active only) Activity against pathogen Cellular toxicity profile Animal (Active v. placebo) Efficacy in preventing infection Safety Human (clinical) (Active v. placebo) Safety in low-risk individuals (Phase 1) Safety in representative population (Phase 2) Effectiveness (Phase 3)

27. clinical trial sites in 2003 Antwerp, Belgium London, UK New York, USA Cincinnati, USA Washington, USA Providence, USA Philadelphia, USA Los Angeles, USA Baltimore, USA Norfolk, USA Houston, USA Ghana Birmingham, USA Côte d’Ivoire India Chiang Rai, Thailand Miami, USA Dominican Republic Nigeria Uganda Yaoundé, Cameroon Tanzania Malawi Zimbabwe Zambia Brazil Botswana South Africa Alliance for Microbicide Development

28. Laboratory Testing 2-6 Years Phase 1 1 Year Phase 2 2 Years Phase 3 3.5 Years Phase 1 and 2 penile and rectal studies, HIV+, etc. 10 + Years Timeline Source: Tufts Center for the Study of Drug Development

29. Are they only tested on women? • Men are enrolled in some trials: - Baseline studies on the impact of anal intercourse on body • “Male tolerance” studies (impact of candidate microbicides on penis & urethra) • Rectal safety studies being designed

30. Current Product Status • Total pre-clinical 50 • Total clinical 17 • Phase I 10 • Phase I/II 1 • Phase II 4 • Phase I/III 1 • Phase III 1 Source: Alliance for Microbicide Development

31. Where are we now?

32. Development will require significant government investment Large pharmaceutical companies have relatively little interest in pursuing microbicides • perceived low profitability • liability concerns • lack of in-house expertise • uncertain regulatory environment For the last 20 years, almost all funding for contraceptive development and related research has come from governments and foundations.

33. The Microbicide Universe • 35 biotech companies • 44 non-profit research entities • 4 public-sector entities

34. Funding realities and needs Pharmaco-Economic Analysis showed: • Discovery through Phase II costs about $10 mil • Phase III trials can cost anadditional $46-50 mil • If existing portfolio were owned by a single Pharmco, it would need to invest roughly $775 million over the next five years to ensure success • BUT, at 2002 levels, only $230 million available from governmental and philanthropic grants Therefore, $500 million shortfall at least !

35. The Advocates’ Message • There is a broad-based, demonstrable demand for user-controlled prevention methods • North American and European Union investment in microbicide research and development should be • substantially increased in the coming year, and • raised annually until first products reach the market. • Without this investment, we may not see user-controlled HIV prevention tools available within this decade.

36. Global Campaign for Microbicides • Unifying umbrella for NGO activism and interaction with scientific community • 25 active partner organizations; 200 endorsing groups worldwide • Served by two secretariats with small core staffs – one in Washington and one in London • Centralized fundraising and financial support to partner groups • International steering committee

37. GOALS Awareness Acceleration Access Accountability TOOLS Grassroots organizing Policy advocacy Lobbying Political mobilization Social science research NGO capacity building The Global Campaign’s

38. Currently organizing with... • Global North Partners in: • Canada UK • Ireland US • Global South Partners in: • Kenya Ghana • Uganda India • South Africa Thailand • Evolving partnerships & endorsers in • many other countries!

39. Microbicide Development Act of 2003 (S. 859) • Will authorize funding increases as needed • Will require the NIH to: • establish a branch dedicated to microbicide research -- thus creating a single line of administrative accountability for progress • expand and coordinate the research efforts of all the federal branches working on microbicides (NIH, CDC and USAID)

40. What you can do as an individual... 1) Find out where the Global Campaign is active in your area by looking on www.global-campaign.org, or e-mailing us at info@global-campaign.org 2) Sign up to get our bi-weekly e-newsletter, GC News 3) Get any organizations, community groups, or networks you are involved with to host a program on microbicides. 4) Sign the Global Campaign petition and help collect signatures.

41. Your organization canendorse the Global Campaign It’s free. Just fill out the form and then: • Hold briefings for your constituency (members, staff, colleagues, volunteers, board, etc.) • Put microbicides in your group’s advocacy agenda • Talk about them in your newsletter and local media • Whatever suits your organization

42. 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 over 3 years (including women, men and children)

43. When do we expect a microbicide? That depends on us.... With sufficient investment and political will, we could have a new prevention option in 5 -7 years Our Campaign motto • The best time to plant a tree is 20 years ago, the next best time is now! • African proverb