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Microbicides: New Hope for Prevention of HIV and other STIs

Microbicides: New Hope for Prevention of HIV and other STIs. Pamina M. Gorbach UCLA- SPH & Medicine. The Global Impact of HIV. Women are disproportionately affected by AIDS: In Sub-Saharan Africa, young women are 4 times more likely to be infected than young men.

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Microbicides: New Hope for Prevention of HIV and other STIs

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  1. Microbicides:New Hope for Preventionof HIV and other STIs Pamina M. Gorbach UCLA- SPH & Medicine

  2. The Global Impact of HIV Women are disproportionately affected by AIDS: In Sub-Saharan Africa, young women are 4 times more likely to be infected than young men.

  3. Why We Need Female Controlled Methods Biology • Women are 2-4 times more likely than men to get HIV from unprotected sex Economics • Economic need or dependency • Less able to assert their rights Social & Cultural • Gender norms about sexuality • Gender based violence Current methods (abstinence, fidelity, and condom use) often require male consent, participation & cooperation

  4. Protection in Primary Partnerships: Difficult to Achieve • People generally are willing to to use condoms with new partners, or during casual or commercial sex • But once “trust” enters the equation the condom comes off • Sex with a primary partner is the biggest source of HIV infection among women globally

  5. What is a Microbicide? A substance that can reduce the transmission of HIV and other STI pathogens when applied topically to genital mucosal surfaces -vaginally and, possibly, rectally. They are not yet available. • First Generation: • Gels and creams • In the future: • Sponges, vaginal rings • Gels with barrier devices © Salam Dahbor, Courtesy Doubleshots Studio • Possibly use of oral antiretroviral therapy, (tenofovir), for pre-exposure prophylaxis (PrEP) to prevent HIV infection.

  6. What Do We Need from Microbicides? • To be contraceptive and non-contraceptive • To reduce risk of other STIs • To be safe and non-irritating • To be inexpensive and available over the counter • To be possibly used without partner’s cooperation or even awareness

  7. 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

  8. 1. boosts vagina’s natural defenses - Buffergel 2. surfactants 4. anti-retrovirals =Tenofovir, UC781, TMC120 3. entry inhibitors = CS, Carraguard, Pro2000 Source: Shattock, R.; Moore, J. Inhibiting Sexual Transmission of HIV-1 Infection. Nature Reviews Microbiology. Vol 1, October 2003.

  9. MICROBICIDES IN CLINICAL TRIALS May ‘07 © Alliance for Microbicide Development

  10. 3 Products Furthest Along

  11. Planned Microbicide Trials There are 11 microbicide candidates in clinical development and over 30 in preclinical development

  12. How Effective Will Microbicides Be? First microbicides may be 40-60% protective Second generation may be 60-80% 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.” The Economics of Microbicide Development: A case for investment. THe Rockefeller Foundation. 2002

  13. 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

  14. The Product Pipeline in 2007 3 products 3 products 4products 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 200-400 people 3,000-10,000 people 25 – 40 people Simultaneous studies in some cases: HIV+, penile & rectal safety 10 or more years Source: Alliance Pipeline Update, first week of every month - http://www.microbicide.org/publications

  15. Clinical Trial Sites in 2007 EUROPE - Belgium: Phase I/II THE AMERICAS: -United States: Phase I, II, IIB -Brazil: Phase II ASIA -India: Phase II -Thailand: Phase I WEST AFRICA: -Cameroon: Phase I, II AUSTRALIA - Phase 1 SUB-SAHARAN AFRICA: -Botswana: -Kenya: planned -Madagascar: Phase -Malawi: Phase II, IIB -Rwanda: Phase I/II -South Africa: Phase I, IIB, III -Tanzania: Phase III -Uganda: Phase III -Zambia: Phase IIB, III -Zimbabwe: Phase I, II, IIB Source: Alliance for Microbicide Development

  16. When can we expect a microbicide? • Earliest results from current Phase 3 trials in 2008-2009 • If shown to be effective, a microbicide may be available in a few countries via introductory studies in the next 5 years • If not, we will have to wait for results from second generation products

  17. The Microbicide Trials Network (MTN) is a worldwide collaborative clinical trials network that evaluates the safety and efficacy of microbicides designed to prevent HIV transmission and will support licensure of topical microbicide products. The MTN plans to develop and/or execute 15 separate clinical trials of microbicides between 2006 and 2013. Network led by Sharon Hillier at Magee Women’s Health Foundation/U Pitts: Dr. Ian McGowan is a Co-principal investigator. PMG – Chair of Behavioral Research Committee

  18. Topics on BRC Scientific Agenda:Adherence & Acceptability

  19. Experience of a Phase III Participant Family Planning Condoms + experimental gel Informed consent for screening Informed consent to enroll. Condoms + placebo Recruitment: Participant receives information about the trial in their own language Screening Visit 1: Education about the trial, HIV and pregnancy test, STI tests and treatment, baseline data collected Screening Visit 2: Results of tests, counselling, reinforce education about trial Randomisation: Participant assigned by chance to a group.

  20. Handheld screen with 035 adherence question (n=400 in Malawi Courtesy of Barbara Mensch, Population Council

  21. Malawi – Pop Council School Study Courtesy of Barbara Mensch, Population Council

  22. Microbicide Research in LA • Focus on rectal microbicide development • Principle research effort led by UCLA: • Microbicide Development Program (MDP) – U19 funded by NIAID • Preparedness: • NARLA: Project 2 -

  23. Rectal Microbicides • Many people (women and men) need microbicides for anal intercourse • Creating an effective rectal microbicide is scientifically more complicated • Vaginal microbicides must be accurately labeled Photo courtesy of www.lifelube.org

  24. PI: Peter Anton & Ian McGowan. Collaborative effort with NIH and industry to initiate multidisciplinary research on rectal microbicides through multiple projects including: • Preclinical Evaluation of HIV Rectal Microbicides • Rectal Health, Behaviors and Product Acceptability • Phase I trial of a rectal microbicide UC-781 a reverse transcriptase (RT) microbicide • These studies are designed to help develop a product that people will find acceptable and actually use. Findings will help guide the selection of the formulation used in human trials.

  25. Rectal Health, Behaviors and Microbicide Acceptability – U19 Project 3 - Gorbach Two Components: • Integrated behavioral and clinical study of receptive anal intercourse • Applicator method acceptability (preference) study • 2 sites: LA, Baltimore

  26. “AMP” Ano-rectal Microbicide Project 896 participants ½ in LA ½ men & ½ women ½ HIV positive ½ report recent RAI All complete: STI/HIV testing HRA Clinical exam Behavioral Questionnaire Already ~ 219 studied!

  27. Why This Study? Preparedness… • Rectal microbicides are in development. • The public knows little about rectal microbicides. • There will soon be clinical trials of rectal microbicides that will need participation from those who need and will use them. A Phase I trial started in LA (U19). • There is a need for specially designed materials to introduce the public to rectal microbicides (both within clinical trials and beyond) to optimize their value as a method of HIV prevention. • Preliminary work with communities is necessary to prevent misinformation and enhance acceptability.

  28. Study Goals 1. Assess the best format to deliver educational materials about rectal microbicides to potential participants in clinical trials, and 2. Consider potential barriers to microbicide trial participation by analyzing factors that facilitate enrollment and retention in a microbicide trial registry in a cohort of men in Los Angeles N=>106 already! Total cohort 450 men

  29. Materials Developed (Video & Brochure) in LA in 2006 Community sites: Friends, APLA, UCLA-CARE

  30. What if microbicides don’t work? • Build on the lessons in development of new technologies – process is iterative. • But….keep perspective. Failure of one product that utilizes one mechanism of action in microbicide does not mean all microbicides are doomed. Many other products and other mechanisms in the pipeline • Future microbicide will likely use combination mechanisms and will likely include coitally & non-coitally dependent methods • Setbacks may happen but science must move forward – there is an epidemic…

  31. Imagine a Full Spectrum of Interventions Prior to exposure Point of transmission Treatment • Rights-focused behaviourchange • VCT • STI screening and treatment • Preventative Vaccines • PREP • Male circumcision • Male and female condoms and lube • PMTCT • Clean injecting equipment • Vaginal and rectal microbicides • Cervical barriers • PEP • Anti-retroviral treatment • Treatment for opportunistic infections • Basic care/nutrition • Prevention for positives • Education and behavior change • Therapeutic vaccines

  32. The global and local need for microbicides is urgent as women and men continue to become infected and suffer from HIV • There are vaginal & rectal microbicides in clinical trials now • Microbicides offer great potential to impact HIV epidemics –one more • prevention tool - self not partner controlled Frank Herholdt, Courtesy of Microbicide Development Project

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