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2. PARTICIPATION IN HIV CURE RESEARCH HIV Cure Research Training Curriculum Module developed by: Karine Dubé, DrPH Candidate, The University of North Carolina at Chapel Hill Matt Sharp, National Martin Delaney Community Advisory Board (CAB) Leader September 2015 with input from Sidaction The HIV CURE research training curriculum is a collaborative project aimed at making HIV cure research science accessible to the community and the HIV research field.

3. Module Objectives Describe HIV cure clinical research in the context of the broader HIV research agenda Discuss inclusion of people living with HIV in cure research, including under-representation of certain populations Provide overview of the various types of HIV cure-related studies enrolling participants Provide the patient perspective and explore considerations for participation in HIV cure-related research, such as managing expectations Start to understand factors that would facilitate or deter participation in HIV cure-related research

4. HIV Cure Clinical Research Why it matters Clinical research is the gold standard for moving any kind of medical research forward HIV/AIDS clinical studies are not new but there are important differences with HIV cure-related research Clinical research is the gold standard for moving any kind of medical research forward HIV/AIDS clinical studies are not new but there are important differences with HIV cure-related research Clinical research Essential to advancing medical discovery and reducing the burden of disease and illness 2.5 million new HIV/AIDS infections per year; > 34 million people living with HIV worldwide Rationale for finding a cure for HIV infection Allows us to collect data and test hypotheses formulated from observations and/or intuition Essential to advancing medical discovery and reducing the burden of disease and illness 2.5 million new HIV/AIDS infections per year; > 34 million people living with HIV worldwide Rationale for finding a cure for HIV infection Allows us to collect data and test hypotheses formulated from observations and/or intuition

5. Definitions of HIV ‘Cure’ Very small numbers of HIV infected cells persist below detectable levels while off treatment Functional Cure/Remission Complete eradication of virus from the body Sterilizing Cure

6. HIV treatment, prevention and ‘cure’ research Research typeParticipant statusResearch goalSelected ethical issues HIV treatmentHIV positiveEffective suppression of virus, boosting immune system All phases; risk of drug side- effects; adherence problems HIV preventionHIV negativeEffective methods of preventing HIV acquisition Seroconversion of participants during trial; behavioral disinhibition HIV ‘cure’HIV positiveInterventions to permanently suppress or eradicate HIV Early phase; risk of intervention side- effects; existence of known effective treatment Slide Credit: Stuart Rennie, University of North Carolina at Chapel Hill

7. Individuals Needed for HIV Cure-Related Studies Will be as diverse as the HIV population itself Johnston and Heitzeg, ‘Sex, Age, Race and Intervention Type in Clinical Studies of HIV Cure: A Systematic Review’, ARHR 2015

8. Under-Represented Populations in HIV Cure-Related Research Johnston and Heitzeg, ‘Sex, Age, Race and Intervention Type in Clinical Studies of HIV Cure: A Systematic Review’, ARHR 2015

9. Under-Represented Populations in HIV Cure-Related Research Women, older people and non-whites do not reflect national or international burden of HIV infection More data needed to determine associations between demographic characteristics and safety/efficacy of HIV curative research strategies Study recommends that Authors should report basic demographic data (sex, age, race) Outcomes (safety and efficacy) should be analyzed by demographic variables and results reported If possible, studies should be powered to explore differences (but difficult for early phase research) To facilitate meta-analyses, standardized endpoints should be taken Johnston and Heitzeg, ‘Sex, Age, Race and Intervention Type in Clinical Studies of HIV Cure: A Systematic Review’, ARHR 2015

10. Minority Participation in Clinical Research

11. Types of Studies Enrolling Participants Strategies Adoptive immuno-therapy Antibodies Gene ‘therapies’ – including those for people with cancer Latency-reversing agents Stem cell transplantation ‘Therapeutic’ vaccines Treatment intensification Combinations Observational studies or cell donations Treatment Action Group (TAG) Research Towards a Cure Trials http://www.treatmentactiongroup.org/cure/trials

12. Types of Studies Enrolling Participants Treatment Action Group (TAG) Research Towards a Cure Trials http://www.treatmentactiongroup.org/cure/trials

13. Finding a Clinical Study

14. What would facilitate making decisions about whether to participate in HIV cure-related studies?

15. Core Components of Clinical Studies Entry (Inclusion/ Exclusion) Requirements Entry (Inclusion/ Exclusion) Requirements Informed Consent Informed Consent IRB Approved Compensation IRB Approved Compensation Voluntary Enrollment Voluntary Enrollment Study Procedures Study Procedures Time and Commitment Needed Time and Commitment Needed Expected Risks and Benefits Expected Risks and Benefits Ethical Considerations Ethical Considerations Can withdraw at any time Can withdraw at any time

16. HIV Cure-Related Clinical Studies Main Procedures (e.g. Biopsies) Main Procedures (e.g. Biopsies) Phereses Analytical Treatment Interruption? Analytical Treatment Interruption? Side Effects (Expected vs. Unexpected) Side Effects (Expected vs. Unexpected)

17. Language and Terminology Patients vs. subjects vs. participants vs. volunteers (Bromley et al., AJPH 2015) Clinical studies vs. trials vs. experiments (Dubé et al., Trends in Microbiol, 2014) Impact of the word ‘cure’ when early-phase studies will not be curative (Rennie & Tucker) Use of the word ‘therapeutic’ (e.g. gene ‘therapy’ and ‘therapeutic’ vaccine) in the experimental stage (Henderson GE)

18. Managing Expectations

19. Motivators to participation Difference between early phase studies vs. late phase trials Emphasis on personal risks vs. personal benefits and social risks vs. social benefits Social motivators divided between microsocial, mesosocial and macrosocial Barriers to participation Divided between safety concerns, fear/mistrust, discrimination, pragmatic obstacles Difference between hypothetical and actual trial participation Discrepancy between qualitative and quantitative studies Original research articles: Psychometric scale to assess facilitators and inhibitors of enrollment Willingness to Participate in HIV Prevention Research

20. Participation in HIV Treatment Trials Main barriers to participation organized in terms of: 1) Safety concerns/side effects 2) Distrust of researchers 3) Concerns around research design 4) Logistical challenges and 5) Social discrimination Decisions depended on: Perceptions of trials Knowledge about trials Biases of physicians/researchers Lived experiences and psychological context One study (Slomka et al.) employed Health Belief Model: 1) impact of HIV disease on decision; 2) benefits 3) barriers; 4) triggers/cues; and 5) self- efficacy towards involvement in research Risk-benefit ratios Clinical contact factors (Worthington et al.) as largest confounder for personal characteristics

21. Cancer Literature Factors promoting participation in cancer trials: 1)Trusting relationship between researcher and patient 2)Communication processes and informed consent Reasons for not participating included: 1)Patients decisions 2)Researchers choosing not to offer trial involvement 3)Lack of knowledge 4)Patients not meeting I/E criteria 5)Concerns around profit-driven motives of pharmaceutical companies Other themes: Tension between conflicting objectives of clinical care/treatment and research Role of support Concerns around impact on health insurance Hope for therapeutic benefit and altruism embedded Entire therapeutic trajectory

22. What would be some issues to consider to participate in HIV cure-related studies?

23. Dutch HIV Association Survey (n = 458) F. Verdult, with HIV Vereniging Nederland (Dutch HIV association) Internet survey (2012) 86% self-reported to be in good health 94% on cART 62% reported positive effects of HIV on their life 72% said it was very important for them to be cured of HIV

24. Five top ten disadvantages are psycho-social related factors Dutch HIV Association Survey (n = 458)

25. A sterilizing cure is very desirable for most of respondents Dutch HIV Association Survey (n = 458)

26. M.P. Arnold (Fred Hutchinson Cancer Research Center, Legacy project) Internet survey (2011-2012), n = 2262 PLWH 81% self-reported to be in good health 93% on cART 87% viral load <50 copies/mL 55% CD4>500 cells/mm 3 Arnold et al., J. Viral Eradication 2015 U.S. Survey (n = 2, 262)

27. Willingness to participate in HCRT including treatment interruptions 63% for personal benefits 55% for social benefits 44% for scientific benefit Factors influencing participation (important/very important) 77% current health 58% financial compensation U.S. Survey (n = 2, 262)

28. Focused on risks and benefits of HIV cure-related clinical studies For more details, please contact: Jeff Taylor: jefftaylorps@gmail.com Co-Investigators: David Evans (devrex@gmail.com) and Paris Mullen (parismullen@hotmail.com) Karine Dubé: karine_dube@med.unc.edu New Survey Objectives: To better understand factors that act as motivators and/or deterrents of participation in HIV cure-related studies To explore how various stakeholders perceive risks and benefits of HIV cure-related studies To understand some of the practical and pragmatic issues that affect participation in HIV cure-related studies to facilitate ethical conduct

29. The Voice of the Patient FDA’s Patient-Focused Drug Development Initiative Source: http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/ UCM389379.pdf

30. Developing Country Considerations Research landscape Funded research, capacity, implementation of research Health priorities and HIV cure-related research Scalability Informed consent, literacy and meaning of HIV cure Treatment interruption Risk determination Partner involvement Credit: Stuart Rennie, University of North Carolina at Chapel Hill

31. Community Participation and Driving Principles

32. Resources Community Participation Resources DAIDS Learning Portal: Community Advisory Boards (eLearning) Introduction to Clinical Research and the Clinical Research Progress (eLearning) CAB Workshop Community Discussion Group (Social Learning Community) HANC: AVAC: Good Participatory Practice Guidelines (document, toolkit, workshops) FHI 360: Stakeholder Engagement Toolkit for HIV Prevention Trials CUREiculum: http://www.avac.org/cureiculum

33. Acknowledgements