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Microbicides: Science, research, and overview of the field Dr Kamini Walia, Indian Council of Medical Research, New Delhi Bindiya Patel, Global Campaign for Microbicides A "microbicide" is any substance that can substantially reduce transmission of sexually transmitted infections (STIs) and HIV when applied either in the vagina or rectum. Why Microbicide? Many women acquire HIV or STDs from a steady partner Consistent condom use difficult to achieve in the longer term relationships • Few interventions have achieved consistent use in more than 30% of couples Contraceptive aspect of existing prevention methods is a major barrier to their use The search for the ideal microbicide • • Rationale: Unprotected Sex-reproduction, coercion, pleasure Active against a range of sexually transmitted pathogens • Not irritating to mucosal surfaces • +/- spermicidal formulations • Acceptable (odor, color, taste, lubricity, portability, “stealth factor”) Imagine a Full Spectrum of Interventions Point of transmission Prior to exposure Treatment •Rights-focused behaviour change •Male and female condoms and lube •Anti-retroviral treatment •VCT •PMTCT •STI screening and treatment •Clean injecting equipment •Treatment for opportunistic infections •Male circumcision •PEP •Preventative vaccines •Vaginal and rectal microbicides •PREP •Cervical barriers •Basic care/nutrition •Prevention for positives •Education and behavior change •Therapeutic vaccines Science and Research Overview What is the most critical need in research? Proof of Concept There is no definitive data as yet establishing that any product applied topically in humans can prevent HIV infection. Desirable Properties of an Ideal Vaginal Microbicide Retain activity in the presence of semen and over a broad pH range, ideally for several hours Products must not disrupt the normal vaginal flora Agents and vehicles for delivery must be compatible for use with condoms and delivery systems Ensure adequate distribution and retention in vagina 1. boosts vagina’s natural defenses 4. anti-retrovirals 2. surfactants 3. entry inhibitors Source: Shattock, R.; Moore, J. Inhibiting Sexual Transmission of HIV-1 Infection. Nature Reviews Microbiology. Vol 1, October 2003. Steps in research Drug discovery In vitro testing Animal model testing (safety) Formulation Scale up manufacturing Phase I early safety Phase II expanded safety Phase IIb Phase III efficacy Social science research The Product Pipeline in 2008 3 products 3 products 30+ products Laboratory Testing 2-6 Years 4 products Phase I (safety) Phase II (safety) Phase III (efficacy) 1 to 6 Months Up to 2 Years 2 to 4 Years 25 – 40 people 200-400 people 3,000-10,000 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 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 I 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 Products Furthest Along Product Trial sponsor # women to be enrolled Buffer Gel HPTN035-NIH 3,100 women South Africa, Malawi, Zambia, Zimbabwe and Philadelphia April 2009 Carraguard Population Council 6,202 women South Africa – 3 locations Feb 2008 PRO2000 (.5%) HPTN035-NIH 3,100 women South Africa, Malawi, Zambia, Zimbabwe and Philadelphia April 2009 PRO2000 (.5 and 2%) DFID, MRC 9,763 women South Africa, Uganda, Zambia, Tanzania December 2009 1% Tenofovir Gel CAPRISA 980 women South Africa 2010 Location Preliminary results expected in Experience of a Phase III Participant Family Planning Informed consent for screening Informed consent to enroll. Condoms + experimental gel Condoms + comparator gel 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, counseling, reinforce education about trial Randomization: Participant assigned by chance to a group. Microbicides which are antiretrovirals Have high specificity and potency Not effective against other STIs Potential for drug resistance with a single drug The case for combination microbicides The arguments for using inhibitors in combination for prevention are as strong as they are for treatment. • Increased breadth of coverage against divergent strains. • Possible synergy, creating dose-sparing effects. • Reduced probability of transmitting viruses resistant to any single inhibitor. • BUT the approval process not yet clear When can we expect a microbicide? Earliest results from current Phase III 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 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 The Actors in the Microbicides Field Range of Players Researchers (lab, trials, social science) Trial sponsors Funders Advocates Who is doing Microbicide R&D? Public–sector entities Non-profit research entities Small biopharmaceutical companies Large pharmaceutical have steered clear… o o o o Perceived low profitability Lack of proof of concept Few expert in vaginal products “Developing world” considered to be primary customers Who is paying for this work? Public institutions (86%) Philanthropic sources (12%) Commercial sector (2%) Total of US $222 Million in 2006 http://hivresourcestracking.org Indian players ICMR: NARI, Pune, NIRRH, Mumbai CSIR:CDRI, Lucknow DRDO:DIPAS, New Delhi YRG, Chennai Indian Network of NGOs Advocacy Aims • Sufficient resources for the entire field • R&Ds • Social science research • Advocacy • Community involvement • Community and political support so that trials can take place • Individuals and communities have a voice in the decisions that affect their lives • Access to products once they are available What You Can Do Get in touch with local advocates Sign up for newsletters, listservs Join / endorse groups Educate yourself and others: • Presentations • Events • Web-links • Newsletters • Use our film • Fact sheets www.global-campaign.org, www.rectalmicrobicides.org, www.microbicide.org