Microbicides Envision a product that could save lives Your name here

2.7 million new infections annually 33.4 million people now live with HIV/AIDS Amongst newly infected people: 50% are women (higher in some areas) 95% live in developing countries 80–90% of HIV+ people in southern Africa do not know they have HIV

<20% Sex workers with access to behaviour change programmes 11% HIV+ pregnant women with access to PMTCT 10–12% Adults in Africa accessing HIV testing 9% Men who have sex with men with access to appropriate behaviour change programmes 9% Sexually active people with access to male condoms 8% Injection drug users with access to harm reduction programmes Percentage of at-risk people with access to HIV prevention 0 Rose to 45% recently Global HIV Prevention Working Group 2008; WHO/UNAIDS/UNICEF 2007

The Global Campaign for Microbicides works to: Ensure accountability; as science proceeds, protect the public interest. Mobilise demand and investment for research and development of new prevention technologies. Conduct advocacy for development, introduction, access, and use of new prevention products.

What is a microbicide? A new type of product being developed that people could use vaginally or rectally to protect themselves from HIV and possibly other sexually transmitted infections.

How might a microbicide be delivered? A suppository or a gel applied with an applicator before sex Contents of a vaginal ring that stays in place for up to a month Developing a film, vaginal tablet, soft-gel capsule

Protection Technology Economic opportunities Social power Source: Brady, Martha. Population Council, Conceptual Framework What women need to protect themselves

We need microbicides that: Are both contraceptive and not contraceptive. Help reduce the risk of getting other sexually transmitted infections. Are inexpensive and easily available. Can be used without a partner’s active cooperation. Can be used vaginally or rectally. Can be used by HIV+ people (products not based on ARVs).

Why would HIV+ people want microbicides? To reduce the risk of co-infection with other HIV strains. To reduce the risk of other sexually transmitted infections, and yeast and bladder infections. To allow conception whilst protecting partner.

PrEP Clean injecting equipment Cervical barriers: vaginal diaphragms PMTCT Vaccines Voluntary counselling and testing HIV Prevention Microbicides Male and female condoms Male circumcision PEP

HIV prevention Male and female condoms Circumcision Vaccines Needle exchange VCT PEP PrEP Treatment for HIV+ partner Vaginal and rectal microbicides Prevention of vertical transmission (PMTCT)

With Primary PartnerWith Casual or Outside Partner Why condoms are not enough Measure Evaluation. 1997–

Source: Shattock R, Moore J. Inhibiting Sexual Transmission of HIV-1 Infection. Nature Reviews Microbiology. Vol. 1, October Surfactants 3. Block binding4. Stop replication 1. Boost vagina’s natural defences 5. Future possibility *STDs: sexually transmitted diseases *

Early-stage concepts Preclinical testing More than 50 candidates Early human safety trials 1 in large-scale efficacy trials The product pipeline Source: Alliance for Microbicide Development

Outcomes of past studies Signs of efficacyNo efficacy Safe Carraguard® BufferGel® PRO % Trend toward harm Nonoxynol-9 Savvy Cellulose sulphate

Current and planned late-stage trials Product Trial sponsor # women to be enrolled Location(s)First results expected Tenofovir gel CAPRISA, CONRAD, USAID, FHI 980 womenSouth AfricaEarly 2010 Tenofovir gel MTN 1,680 (in gel arms of trial) South Africa, Uganda, Zambia, Zimbabwe 2012 Dapivirine (TMC 120) IPM TBDVariousTBD Tenofovir gel MRC/UVRI TBDMozambique, South Africa, Tanzania, Uganda, Zambia TBD Source: Alliance for Microbicide Development

Clinical trial sites in 2010 Source: Alliance for Microbicide Development THE AMERICAS United States: Phase 1, 1/ 2, 2 Puerto Rico: Phase 1 Dominican Republic: Phase 1 SUB-SAHARAN AFRICA Kenya: Phase 1 South Africa: Phase 1, 2B, 3 Tanzania: Phase 3 Uganda: Phase 2, 3 Zambia: Phase 3 Zimbabwe: Phase 3 ASIA/PACIFIC Thailand: Phase 1 Australia: Phase 1/2

Experience of a trial participant Recruitment: Participant receives information about the trial in her own language Screening Visit 1: Education about the trial, HIV and pregnancy test, sexually transmitted infection tests and treatment, baseline data collected Screening Visit 2: Results of tests, counselling, education about trial reinforced Randomisation: Participant assigned by chance to a group Family Planning Informed consent for screening Informed consent to enrol Condoms + placebo Condoms + experimental gel

When can we expect a microbicide? Results of CAPRISA 004 study of tenofovir gel announced in July Found safe and effective: 39% reduction in infections A larger trial now needed to confirm the results – then one to two years for product review and licensing in each country

Who is doing the research? Research entityExamplesFunding sources Not-for-profit health groups and academic institutions MTN, CONRAD, FHI, CAPRISA Governments (South Africa DST, US NIH, UK DFID), philanthropic foundations Public-private partnerships IPMEuropean/US/Canadian governments, philanthropic foundations, UNFPA, World Bank Smaller pharmaceutical companies Endo StarPharma Venture capital, some government grants

Comparing microbicides: ARV vs. no ARV ARVNo ARV More potent against HIV May be long lasting Not contraceptive Could work against HIV and other sexually transmitted infections Could be contraceptive May cause more side effects May cause resistance Unlikely to protect against other sexually transmitted infections May be less potent against HIV Must be used at time of sex Disadvantages Advantages

If ARV-based microbicides work… 1. Only taken if you KNOW you are HIV negative. – So regular HIV testing is necessary. 2. May be available by prescription only. – So access to a qualified health care provider is necessary. 3. Only the dosing used in trials is known to work. – For now, must be applied daily or before sex.

What is drug resistance? HIV makes thousands of copies of itself daily. Every time HIV copies itself, errors can occur, like typing errors on a page. These are mutations—changes that can make the virus weaker or stronger. A mutation that makes HIV able to resist an ARV drug = drug-resistant HIV.

Drug resistance from microbicides? Most likely when using only one drug or one type of ARV. Can become HIV+ whilst using ARV-based microbicide. Continued use if you do not know you are HIV+ may lead to resistance. Options for treatment may be more limited— you might pass on resistant virus. There are unanswered questions at this point.

Questions women have about microbicides in general If I use a microbicide, how will I make my man use a condom? What will they say about me? How much will it cost? Where will I get it?

Questions women have about ARV-based microbicides Will it make me sick? Can I use an ARV- based microbicide when I am pregnant? Will it hurt my baby? What about breastfeeding? If I think my man has HIV, but I do not know for sure, will I be able to get microbicides?

Advocates call for next steps Research and develop microbicides that are: – ARV based and not ARV based. – Contraceptive, non-contraceptive, and broad spectrum. – Designed specifically for vaginal use and rectal use. Conduct more research into resistance, alternate dosing, and impact on pregnancy and breastfeeding. Call for action on access issues: cost, testing, and prescription only. Increase community engagement. Ensure ethical standards and dialogue.

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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 Frank Herholdt, Courtesy of Microbicide Development Project

“How do you know that?” The notes for this slide list the sources for facts in this presentation. You can cite these as the sources for your information. This list includes sources for facts and statistics that are not well known. We do not list sources here for commonly known statistics.