1. Rolling out PrEP in Latin America Fabio Mesquita fabio.mesquita@aids.gov.br Marrakesh, May 9 – 12 2016

2. Summary Oral pre-exposure prophylaxis to HIV Rolling out PrEP in Latin America PrEP in Brazil

3. Summary Oral pre-exposure prophylaxis to HIV Rolling out PrEP in Latin America PrEP in Brazil

4. Oral pre-exposure prophylaxis to HIV PrEP – Oral PrEP is the use of ARV drugs by HIV-uninfected people to block HIV infection before exposure Available at www.who.int/hiv; access on April 25, 2016www.who.int/hiv

5. Reccomendations PrEP WHO Year Guideline (year of publication) 201220142015 Rationale Demonstration projects Randomized controlled trials Systematic reviews Key population Serodiscordant couples MSM Transgender people People who inject drugs Sex workers Incarcerated people and closed settings People at substantial risk of HIV infection Adapted from www.who.int/hiv; access on April 25, 2016www.who.int/hiv

6. Recommendation Oral PrEP containing TDF should be offered as an additional prevention choice for people at substantial risk of HIV infection, as part of combination HIV prevention approaches (strong recommendation, high-quality evidence). WHO PrEP recommendation New Available at www.who.int/hiv, accessed April 25, 2016www.who.int/hiv

7. Summary Oral pre-exposure prophylaxis to HIV Rolling out PrEP in Latin America PrEP in Brazil

8. Ongoing PrEP studies Available at www.who.int/hiv; access on April 25, 2016www.who.int/hiv

9. Status of PrEP in Latin America On going studies and implementation Brasil Demonstrative and implementation studies Ecuador Demonstrative study Peru Demonstrative study (MSM,Trans and serodiscordant couples) Argentina First phase study with transgender Discussions initiated Mexico Serodiscordant couples, transgenders and sexworkers Panama High risk MSM, trans, serodiscordant couples Costa Rica Participation of the civil society PrEP in private clinics only El Salvador Civil society Rep Dominicana Cost-benefits study Cuba High risk population Pregnant women

10. Ongoing and Planned PrEP Open Label, Demonstration and Implementation Projects in Latin America Trial/ProjectSponsor/FunderType/CategoryLocationPopulationDesign/Key questionsStatusStatus Details PrEP Brasil Oswaldo Cruz Foundation; University of Sao Paulo; Centro de Referência e Treinamento DST AIDS Demonstration Project Brazil MSM; transgender women Enrolled 409 MSM and transgender women to assess acceptability, feasibility and safety of daily, oral TDF/FTC as PrEP over 12 months. Continuing for an additional 48 weeks and enrolling another 50 participants in two sites. Ongoing **Preliminary results presented in July 2015 show high uptake of PrEP, with higher uptake among those at increased risk and with an existing awareness of PrEP.** Ongoing; enrollment completed end-March 2015. Expected completion end- March 2016. iPrEx OLE Sponsored/funded by DAIDS/NIH, through a grant to the Gladstone Institutes. Open label extension Brazil, Peru, Ecuador, South Africa, Thailand, US MSM and transgender women Continuation of the iPrEx study designed to provide additional information about the safety of PrEP and the behavior of people taking PrEP over a longer term. Completed **Results show PrEP provides a high degree of protection against HIV infection, even for individuals who miss daily doses; high Interest in PrEP; longer-term evidence of safety and efficacy; and no sign of increased risk behavior among PrEP users.** Available at http://www.avac.org/sites/default/files/resource-files/PrEP_Trials_Demonstration_Projects_April_2016.pdf; access on April 25, 2016http://www.avac.org/sites/default/files/resource-files/PrEP_Trials_Demonstration_Projects_April_2016.pdf

12. iPrEX Study Team 2499 MSM (Peru, Ecuador, South Africa, Brazil, Thailand, United States) TDF/FTC x Placebo

13. Grant RM et al. N Engl J Med 2010;363:2587-2599 iPREX Study

14. Kaplan–Meier Estimates of Time to HIV Infection (Modified Intention-to-Treat Population). Grant RM et al. N Engl J Med 2010;363:2587-2599 iPrEX Study Team Effectiveness: 44% CROI 2011

15. Summary Oral pre-exposure prophylaxis to HIV Rolling out PrEP in Latin America PrEP in Brazil

16. The Combine! Study: Protocol for a Pragmatic Clinical Trial on PEP, PrEP and Combination HIV Prevention Methods in Public Clinics in Brazil Authors: Grangeiro A, et al. (BMJ Open 2015;5:e009021.) Funding: Brazilian Ministry of Health National Council for Scientific and Technological Development FTC 200/ TDF 300MG donated by Gilead

17. Design Controlled pragmatic trial Individuals aged >16 years, from PEP and non PEP services Groups: o Traditional methods only (condom, non-penetrative sex) o Combination methods (traditional, testing, PEP and PrEP during specific period) o PrEP (PrEP only) Non-probabilistic sample of 3,200 individuals (1,600 PEP Group; 1,600 non- PEP Group) Follow-up: 24 months Started: March/2015 and PrEP Group: Jun/2016

18. São Paulo – CRT Population: 11.2 millions AIDS incidence: 21.7/100.000 Fortaleza – H.São José Population: 2.4 millions AIDS incidence: 26.2/100.000 Porto Alegre – Vila dos Comerciários Population: 1,4 millions AIDS incidence: 96,2/100.000 Curitiba – COA Population: 1.7 millions AIDS incidence: 28.9/100.000 Ribeirão Preto – SAE Population: 604.682 AIDS incidence: 28.5/100.000 Study Sites

21. Users profile of PEP group. Projeto Combina, 2014 a 2015 (N=1804) PrEP Group will begin in June/2016

22. PrEP uptake and associated factors among MSM and TGW in the PrEP Brasil demonstration project Brenda Hoagland, Valdilea G. Veloso, Raquel B. De Boni, José Valdez Madruga, Esper G. Kallas, Nilo Martinez Fernandes, Ronaldo I. Moreira, Albert Y. Liu and Beatriz Grinsztejn for the PrEP Brasil Study Team IAS 2015- Vancouver

23. Funding Gilead Sciences. Inc. donated Truvada®

24. Method Sites Fiocruz/RJ University of São Paulo (USP) Referral Center for HIV treatment (CRT/SP) Inclusion criteria – MSM and TGW, ≥ 18 years, presenting sexual risk for HIV infection (reported ≥ 2 male condomless anal sex partners OR ≥ 2 anal sex episodes with HIV positive partner OR STI diagnosis in last 12 months) Exclusion criteria – HIV positive result, HIV acute infection, HBsAG positive, urine protein, creatinine clearence <60, using ARV, using interferon, severe medical comorbidity, unable to return within 45 days

25. (Preliminary Data) 1187 individuals interviewed (pre-screening visit) – 96.3% (MSM) and 4,7% (TGW) – Median age: 29 years – HIV Positive: 9,8%

26. PrEP Uptake Approached N= 986 Potentially eligible N = 798 Tracked N= 490 Included N=409 Predictors for Uptake: - Higher risk - Previous Knowledge of PrEP

27. Awareness of PrEP

28. Interest in use of PrEP

29. In this first PrEP demonstration project for MSM and TGW without prior PrEP experience in a middle-income country, PrEP uptake was high. Interest on PrEP was high in the MSM community. To targeted Trans people community - education activities and a Trans friendly environment can play a major role in getting them to access PrEP services. The higher uptake among those at higher risk and prior PrEP awareness- emphasizes the importance of establishing strategies to improve HIV risk perception and PrEP awareness in the MSM and TGW communities in Brasil.

30. Pre-Exposure Prophylaxis (PrEP) - UNITAID Pre-Exposure Prophylaxis and Linkage to Testing among sexually active older adolescents with substantial HIV Risk in Brazil, Thailand and South Africa Goal: to contribute to a decrease in the incidence of HIV among adolescents for whom PrEP is recommended in Brazil, Thailand and South Africa. The project is part of efforts to accelerate HIV results in adolescents. MSM and Transgender women. Partner's organizations: UNICEF, UNITAID, Brazilian, Thailand, South African Governments and Civil Society. Outputs: 1. To increase the accessibility of PrEP for eligible adolescent population; 2. Demonstrated effective use of PrEP among adolescents enrolled on the project; 3. Generate knowledge on the use of PrEP by eligible adolescents to influence global PrEP guidelines as well as national policies and guidelines in and beyond the three project countries.

31. Pre-Exposure Prophylaxis (PrEP) - UNITAID PrEParedness for the Rollout of Effective HIV Prevention among Key Affected Populations in Brazil, México, and Peru Goal: to contribute to the global efforts for the rollout and further scale up of Pre- Exposure Prophylaxis (PrEP) as an innovation to combination HIV prevention approaches within the national HIV and AIDS health policies of Brazil, Mexico and Peru. MSM and Transgender Women. Implementation institution: FIOTEC/FIOCRUZ Support institution: UNITAID Partner's organizations: Brazilian, Mexican and Peruvian Governments, Civil Society and Cayetano Heredia University. Outcome: to contribute to the delivery, in a combination HIV prevention framework, of evidence-based, integrated, quality PrEP services that are acceptable, accessible, affordable, safe, effective, equitable, and sustainable, particularly among gay and other men that have sex with men (MSM), and transgender women (TGW) living in selected cities of these countries.

32. Biomedical HIV prevention package Available at www.aids.gov.br; access on April 15, 2016www.aids.gov.br

33. PrEP as a public health policy in Brazil (SUS) October 2015: Establishment of a PrEP Technical Advisory Committee (experts and civil society representative) Agenda 2016: Operational (to be define): Characteristic of the service delivery and organization, (states referral centers / research centers/ VCT clinic) Who to access healthcare settings for PrEP, How to offer PrEP (training ) Drug procurement Delivery at public sector but also in the private sector (sale in pharmacies) Monitoring & Evaluation (to be define): Clinical and laboratory monitoring of the patients

34. Programmatic: Protocol (to be delivery in 2016): Technical document with a package of HIV services pre and post TDF/FTC delivery (continuum of care) Key populations (UD, serodiscordant couples, MSM, Transgender people and sex workers) ARV scheme (TDF/FTC). PrEP as a public health policy in Brazil

35. Acknowlegdments Beatriz Grinsztejn-Fiocruz/RJ/Brasil Leandro Sereno- PAHO/Brazil Alexandre Grangeiro-USP/SP João Toledo-DDAHV/MS Brasil

36. Thank you Adele Benzaken DDAHV/SVS/MS adele.benzaken@aids.gov.br