1. Cindra Feuer and Marc-André LeBlanc HRCF, 21 April 2010 ARV-based Prevention

2. 33 million people now live with HIV/AIDS 2.7 million new infections annually Among newly infected people: 50% are women (higher in some areas) 95% live in developing countries 80–90% of all HIV+ people in southern Africa do not know they have HIV

3. Percentage of at-risk people with access to HIV prevention 0 Rose to 45% recently 20406080100 <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 Global HIV Prevention Working Group 2008; WHO/UNAIDS/UNICEF 2007

4. HIV prevention Not ARV-based ARV-based  Male & female condoms  Circumcision  Clean injecting equipment  Vaccines  VCT  PEP  PrEP  Treatment for HIV+ partner  Vaginal and rectal microbicides  Preventing vertical transmission

5. Why test ARVs to prevent HIV?  ARVs already are used to prevent vertical transmission (or PMTCT).  PEP already is used to prevent infection after medical accidents or rape.  Some evidence that lower viral load among HIV+ people on ARVs for treatment reduce risk of transmission to HIV-negative partners  Monkeys that get ARVs prior to exposure are less likely to be infected.

6. Strategies being researched  Oral Pre-Exposure Prophylaxis (PrEP): ARVs taken regularly or before and after exposure might reduce the risk of HIV infection  ARV-based microbicides: ARVs used in gels or vaginal rings or other products that would be inserted in the vagina or rectum to reduce the risk of HIV infection

7. Pre-exposure prophylaxis (PrEP) For example:  Taking pills to prevent malaria when you travel.  Using hormonal contraceptives (injections or pills) to prevent pregnancy.  Taking pills to avoid pneumonia, if you are at risk. Experimental HIV prevention strategy that would use ARVs to protect HIV-negative people from HIV infection Taking medicine to prevent rather than to treat a disease or condition.

8. Safety concerns?  Safety is a critical issue for PrEP use  Look carefully at people with pre-existing conditions: hepatitis B and C, kidney problems, bone density  Pregnancy, post-menopause (osteoporosis), adolescents (bone formation)  Look carefully at drug clearance in people with low body weight, including women and Asians

9. PrEP: When will we know? WhereWhoWhatWhen US (CDC)*Men who have sex with men tenofovir2010 Thailand (CDC)Injection drug userstenofovir2010 Brazil, Ecuador, Peru, US, Thailand, South Africa (iPrEX) Men who have sex with men Truvada2010 Botswana (CDC)Heterosexual men and women Truvada2011 Uganda, Kenya (Partners PrEP) Serodiscordant couples (men and women) tenofovir, Truvada2012 Kenya, Tanzania, South Africa (FEMPrEP) WomenTruvada2012 South Africa, Uganda, Zambia, Zimbabwe (VOICE) Womentenofovir (pill & gel), Truvada 2012

10. What is a microbicide? A suppository or a gel applied with an applicator before sex A vaginal ring that stays in place for up to a month

11. 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).

12. Product Trial sponsor # participants 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 UC781 CONRAD/NIH/MTN TBDUSTBD MIV-150 Population Council TBDUSTBD Microbicides: When will we know?

13. If PrEP and ARV-based microbicides work 1. Only take if you KNOW you are HIV negative.  Regular testing is necessary. 2. May be available by prescription only.  Access to a qualified health care provider is necessary. 3. Only the dosing used in trials is known to work.  PrEP: only daily dosing for now.  ARV-based microbicides: for now, applied daily or shortly before sex.

14. 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.  If a mutation makes HIV able to resist an ARV drug, it is called drug-resistant HIV.

15. Drug resistance  More likely if taking only one drug (or one type of ARV)  Can still become HIV+ using ARV-based prevention  Use by people who don’t know they are HIV+ might lead to resistance?  Options for treatment may be more limited, might pass on resistant virus  Unanswered questions at this point

16. Treatment as prevention  Can it work at population level?  Increased testing = more knowledge of status = less risk-taking  Increased testing = more HIV+ people on treatment = less virus  Less risk-taking + less virus = less transmission? HIV+ people taking ARVs regularly  Does it work at individual level?  Treatment = less virus = less transmission?

17. Treatment as prevention  Test and treat (TNT) / Test, Link to Care Plus Treat TLC-Plus: Theoretical model suggesting that widespread HIV testing and treatment of all those identified as HIV-positive would greatly reduce HIV incidence and improve their health outcomes.  HPTN 065, TLC-Plus: A Study to Evaluate the Feasibility of an Enhanced Test, Link to Care Plus Treat Approach for HIV Prevention in the United States

18. Treatment as prevention HPTN 052: Phase III, two-arm, multi-site, randomized trial to determine the effectiveness of two treatment strategies in preventing the sexual transmission of HIV in HIV-serodiscordant couples.  CROI 2010. ART and Risk of Heterosexual HIV-1 Transmission in HIV-1 Serodiscordant African Couples: A Multinational Prospective Study.

19. Advocates are calling for:  Better access to existing proven prevention options.  Research into new prevention options, both ARV based and not based on ARVs.  Research into drug resistance, alternate dosing, pregnancy and breastfeeding, and a greater variety of drugs.  Attention to access hurdles: more uptake of HIV testing, access to prescribers.  Increased community engagement.

20. Questions?

21. What you can do:  Become better informed.  Check out the resources on the next slide.  Tell your colleagues.  Send them a link or a fact sheet.  Host a discussion forum.  Use this presentation at work or in your community.  Join advocacy efforts.  Contact other HIV prevention advocates in your region.

22. Join the Advocates’ Network: For regular HIV prevention research updates join the AN at www.avac.org/advocatesnetwork Visit us at www.avac.org Stay informed

23. For more information…  PEP: http://tinyurl.com/hivpephttp://tinyurl.com/hivpep  PMTCT: http://tinyurl.com/pmtcthttp://tinyurl.com/pmtct  PrEP: www.prepwatch.orgwww.prepwatch.org  Microbicides  www.global-campaign.org www.global-campaign.org  www.rectalmicrobicides.org www.rectalmicrobicides.org  www.ipm-microbicides.org www.ipm-microbicides.org  www.microbicide.org (Alliance for Microbicide Development) www.microbicide.org  Treatment of HIV+ partner  www.hptn.org (look under HPTN052) www.hptn.org

24. Why condoms are not enough