1. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 A Network of Multidisciplinary Research on ARV-based Prevention Carlos F. Cáceres, MD, PhD Cayetano Heredia University Lima

2. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Key Messages More than 7,000 people continue to become infected around the world every day (approximately 2.7 million per year, UNAIDS). ARV-based prevention (mainly PrEP and ETfP) is now a technical reality and represents an important addition to prevention options. However, it is still not a programmatic reality Barriers of various kinds, including: – Limited awareness – political buy-in (governments, communities), – health systems issues, – cost and cost-effectiveness considerations, – resolving ethical dilemmas, – transformation of technologies (and meanings) by communities A mechanism to exchange information among interested parties around the world is highly relevant

3. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 DNA/Ad5 2010201120122013201420152016 1 234123412341234123412341234 Positive efficacy result No effect Regulatory submission/filing Planned Final results pending DPV ring Oral TDF/FTC Oral TDF Rectal TFV gel TFV gel TMC278 LA Injectable DNA/Ad5 TIMELINE LEGEND Pox-Protein HIV Prevention Options Timeline * ** * Trial end-dates are estimates; due to the nature of clinical trials the actual dates may change. For full trial details, see www.avac.org/pxrd. ** Not all trials included are effectiveness trials. Trials included on this list are mainly phase II/IIb, III/IIIb and IV trials. Bangkok Tenofovir Study/CDC 4370 Partners PrEP Partners PrEP (no placebo) 2008 2005 2009 VOICE/MTN 003 Oral TDF/FTC Oral TDF iPrEx 2007 iPrEx Open-Label Extension (OLE) 2009 FEM-PrEP US FDA approval CAPRISA 004 2007 TDF2 Open-Label Extension TDF2/CDC 4940 TFV gel FACTS 001 Earliest regulatory submission VOICE/MTN 003 2009 MTN 017 Rectal TFV gel DPV Ring The Ring Study/IPM 027 ASPIRE/MTN 020 Earliest regulatory submission Possible TMC278 LA Injectable TMC 278 LA Inject. Pox-Protein Various Phase I/II preliminary and bridging studies RV 144 2004 South Africa Licensure South Africa Research Thai Licensure 2009 HVTN 505 Additional demonstration projects & intermittent PrEP studies CAPRISA 008 FACTS 002 and other adolescent studies Various Phases of Long-Acting Injectables (SSAT 040 & MWRI-01) AVAC Report 2012: Achieving the End – One year and counting. www.avac.org/report2012 Last updated June 2013

4. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Pre-Exposure Prophylaxis Several trials have explored the efficacy of Oral and Topical HIV Pre-Exposure Prophylaxis in various populations, using TDF or TDF/FTC. The US FDA, in mid-2012, approved TDF/FTC oral pills for use in HIV prevention, based on results from clinical trials testing oral PrEP among MSM (Grant et al 2010), and sero-discordant couples (Baeten 2012). – Further supported by the results of the TDF2 study in Botswana (Thigpen 2012). PrEP has the potential to address the need for a female- initiated prevention method for women worldwide who may be unable to negotiate condom use, or find themselves in situations in which condoms are not available or their use is not feasible or desired.

5. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 WHO Guidelines: PrEP Demo Projects In July 2012 WHO released recommendations for Demonstration Projects focused on PrEP. “In countries where HIV transmission occurs in serodiscordant couples and additional HIV prevention choices for them are needed, daily oral PrEP (TDF or TDF-FTC) may be considered“ “In countries where HIV transmission occurs among men and transgender women who have sex with men and additional HIV prevention choices for them are needed, daily oral PrEP (specifically TDF-FTC) may be considered.” It is currently not possible to provide definitive guidance on how best to deliver daily oral PrEP, for which demonstration project research is needed.

6. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Early Treatment for Prevention Early Treatment for Prevention (TasP), has already been recommended for administration to HIV+ individuals with CD4 counts over 350/mm3 in serodiscordant couples (WHO 2012). In 2011, the HPTN 052 trial showed that, among HIV- serodiscordant couples, ART given to the HIV-positive partner with a CD4+ count <550 cells/mm3 decreased HIV transmission by 96% when compared with those who started ART at CD4+ counts <350 cells/mm3 (Cohen et al 2011). Complementary programmatic changes needed at the individual level include scaling-up HIV testing and counseling through strategies such as provider-initiated, and couples, HIV testing and counseling (WHO 2012) and their integration with care, treatment and prevention.

7. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 New Consolidated Guidelines For the use of Antiretroviral Drugs for Treating and Preventing HIV Infection To be Launched TODAY at 14.45 here in IAS 2013

8. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 WHO Guidelines – ETfP As a priority, ART should be initiated in all individuals with severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) and individuals with CD4 count ≤350 cells/mm3 (strong recommendation, moderate- quality evidence). ART should be initiated in all individuals with HIV with CD4 count >350 cells/mm³ and ≤ 500 cells/mm3 regardless of WHO clinical stage (strong recommendation, moderate-quality evidence). ART should be initiated in all individuals with HIV regardless of WHO clinical stage or CD4 count in the following situations: – Individuals with HIV and active TB disease (strong recommendation, low- quality evidence). – Individuals coinfected with HIV and HBV with evidence of severe chronic liver disease (strong recommendation, low-quality evidence). – Partners with HIV in serodiscordant couples should be offered ART to reduce HIV transmission to uninfected partners (strong recomm., high-quality evid.).

9. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Barriers for Implementation Barriers for PrEP – Health systems limitations: High expenditure implied and potential competition with treatment costs Insufficient capacity to increase testing and to manage/monitor the use of new technologies); – Acceptability issues Among potential beneficiaries, potential difficulties in access to information and explaining the use of ARVs for prevention; regular inconsistency in uptake; Among providers and decision makers, concerns about ‘unethical’ distribution of ARVs and a potential emergence of a PrEP drug black market – Epidemiological consequences Errors in PrEP prescription to HIV+ individuals; low adherence and risk compensation leading to high infection rates

10. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Barriers for Implementation Barriers for ETfP – ARVT coverage levels have to be adequate – Health systems have to be prepared – Levels of partner notification have to be higher – Structural components neglected given limited understanding of their operation – Effectiveness of measures already in place is not guaranteed unless targeting, quality and coverage are adequate

11. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 A Network for Multidisciplinary Studies in ARV-Based Prevention (NEMUS) A network allows for the convergence of a number of groups around the world interested in policy, social science, cost/cost- effectiveness, modeling and/or demonstration projects around combination prevention including ARV-based prevention. 1. Discuss opportunities and challenges for implementation of ARV- based prevention, based on existing as well as new evidence generated by individual projects. 2. Foster collaboration in ongoing studies, with a focus on potential: (a) potential comparison of the results of similar studies across countries; (b) diversification of studies to cover various dimensions/models of ARV-based prevention implementation and various target populations.

12. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 A Network for Multidisciplinary Studies in ARV-Based Prevention (NEMUS) 3. Develop concepts and resources for collaboration in the design and implementation of potentially useful studies around ARV-based prevention scale-up, including, for example: (a)policy studies focused on the inclusion of PrEP and ARV-based prevention in combination HIV prevention programs; (b)social impact of ARV-based prevention scale-up; (c)modeling effectiveness and cost-effectiveness studies of its implementation in CP programmes; (d)analysis from the perspective of bioethics (WHO/UNAIDS meeting on ethical issues); (e) demonstration projects. 4. Communicate findings and lessons learned to global stakeholders.

13. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Potential Research Questions Policy Who are the stakeholders? Are they aware? What are the perspectives of each? What is the basis for disagreement? Is it feasible to seek consensus? (what kind of consensus: e.g. to conduct a more thorough assessment of options) Health Systems and Cost/Cost-Effectiveness Are services prepared to offer ARV-Based prevention? What needs to be implemented and what is the cost? Is the proposed programme anticipated to be cost-effective and sustainable? Can the necessary levels of coverage and adherence be reached? Who should be prioritised? Social Science How will people react to introduction of new strategies? Is it likely that they will be resignified? What will happen to other sexual practices? Is there a possibility of stigmatization of users? Will new strategies have an overall positive impact on communities

14. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Example: A Study to Start in Lima “Developing a State-of-the-Art” HIV CP Programme for MSM/TW in Lima with Stakeholder Involvement” Multidisciplinary Study to start later this year – Phase I: Stakeholder Analysis (Policy) – Phase II: Health Systems Assessment Cost of Current and Proposed Prevention Options Cost of Improving Clinic Laboratory Infrastructure – Phase III: Modelling Scenarios of CP in terms of Effectiveness and Cost-Effectiveness – Phase IV: Stakeholder Consensus Building Workshop Involvement of Gladstone, Imperial College, MoH, INS

15. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Estimated Impact of PrEP Implementation among MSM/TW according to levels of coverage, adherence, and prioritization of sub-populations (Gomez et al., 2012) Less adherence iPrEX adherence profile More adherence A. B. Low coverage (5%) High coverage (20%)

16. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 NEMUS: Initial Steps – Exploratory Participation in CROI (March 2013) and PrEP communication meeting (April 2013) to assess interest among researchers and implementers – Informal sessions about this project with other researchers in IAS Conference (Kuala Lumpur) in June 2013, and ASSHH Conference (Paris) in July 2013 In the KL and Paris meetings, the agenda will include initial work on priorities and research questions in multidisciplinary research on ARV- based prevention. Given that audiences of those meetings are different (i.e. the IAS KL conference will gather mainly basic researchers, programmatic implementers, modelers and epidemiologists; the ASSHH Paris meeting will gather mainly social scientists), there will likely be no overlap in the discussion. – Next Phase: Establish a Communications Base and carry out initial agenda

17. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 This Meeting in Kuala Lumpur 1.Summarise the state of the art concerning ARV- based prevention (evidence, challenges) 2.Present the Network of Multidisciplinary Studies on ARV-Based Prevention (goals, communication channels) 3.Start a discussion about trans-disciplinary research questions on ARV-based prevention that are relevant now – In ASSHH focus will be on social science reesearch 4. Contribute to exchanges among actors interested in this field.

18. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Acknowledgments Kevin O’Reilly and Florence Koecklin WHO Tim Hallett, Imperial College London Peter Godfrey-Faussett and Barbara de Zalduondo, UNAIDS Papa-Salif Sow, The Gates Foundation Manoj Kurjan and Helen von Dadelzsen, IAS Mitchell Warren, AVAC Robert Grant and Pedro Goicochea, Gladstone