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PARTICIPATION IN HIV CURE RESEARCH

HIV Cure Research Training CurriculumModule developed by:Karine Dubé, DrPH Candidate, The University of North Carolina at Chapel HillMatt 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.

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

HIV Cure Clinical Research

Why it matters 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 researchClinical

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

Definitions of HIV ‘Cure’

• Very small numbers of HIV infected cells persist below detectable levels while off treatment

• Very small numbers of HIV infected cells persist below detectable levels while off treatment

Functional Cure/RemissionFunctional Cure/Remission

• Complete eradication of virus from the body

• Complete eradication of virus from the body

Sterilizing CureSterilizing Cure

HIV treatment, prevention and ‘cure’ researchResearch type Participant status Research goal Selected ethical

issuesHIV treatment HIV positive Effective

suppression of virus, boosting immune system

All phases; risk of drug side- effects; adherence problems

HIV prevention HIV negative Effective methods of preventing HIV acquisition

Seroconversion of participants during trial; behavioral disinhibition

HIV ‘cure’ HIV positive Interventions 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

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

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

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

Minority Participation in Clinical Research

Types of Studies Enrolling Participants

Strategies Adoptive immuno-therapyAntibodiesGene ‘therapies’ – including those for people with cancer Latency-reversing agentsStem cell transplantation‘Therapeutic’ vaccinesTreatment intensificationCombinations Observational studies or cell donations Treatment Action Group (TAG) Research Towards a Cure Trials

http://www.treatmentactiongroup.org/cure/trials

Types of Studies Enrolling Participants

Treatment Action Group (TAG) Research Towards a Cure Trialshttp://www.treatmentactiongroup.org/cure/trials

Finding a Clinical Study

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

Core Components of Clinical Studies

Entry (Inclusion/Exclusion)

Requirements

Entry (Inclusion/Exclusion)

Requirements

Informed Consent

Informed Consent

IRBApproved

Compensation

IRBApproved

Compensation

Voluntary EnrollmentVoluntary 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

HIV Cure-Related Clinical Studies

Main Procedures

(e.g. Biopsies)

Main Procedures

(e.g. Biopsies)PheresesPhereses

Analytical Treatment

Interruption?

Analytical Treatment

Interruption?

Side Effects(Expected vs. Unexpected)

Side Effects(Expected vs. Unexpected)

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)

Managing Expectations

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

macrosocialBarriers to participation • Divided between safety concerns, fear/mistrust, discrimination, pragmatic

obstacles • Difference between hypothetical and actual trial participation• Discrepancy between qualitative and quantitative studiesOriginal research articles:• Psychometric scale to assess facilitators and inhibitors of enrollment

Willingness to Participate in HIV Prevention Research

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

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: 3) Patients decisions4) Researchers choosing not to offer trial involvement5) Lack of knowledge6) Patients not meeting I/E criteria7) 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

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

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

Five top ten disadvantages are psycho-social related factors

Dutch HIV Association Survey (n = 458)

A sterilizing cure is very desirable for most of respondents

Dutch HIV Association Survey (n = 458)

• 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/mm3

Arnold et al., J. Viral Eradication 2015

U.S. Survey (n = 2, 262)

• 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)

• 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

The Voice of the Patient FDA’s Patient-Focused Drug Development Initiative

Source: http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM389379.pdf

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

Community Participation and Driving Principles

Resources

Community Participation ResourcesDAIDS 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

Acknowledgements