1. Associate Director: CAPRISA - Centre for the AIDS Programme of Research in SA Director: CU-SA Fogarty AITRP Presented at the: GCM and HAVEG Consultation on ethical-legal concerns in HIV vaccine and microbicide trials, Durban September 2006 Adolescents in trials: An ethical- legal analysis Quarraisha Abdool Karim CENTRE FOR THE AIDS PROGRAMME OF RESEARCH IN SOUTH AFRICA C APRISA CAPRISA is a UNAIDS Collaborating Centre for HIV Prevention Research

2. Overview  Why focus on adolescents  Opportunities through inclusion of adolescents  Context of research in adolescents  Concerns about enrolling young people  Ethical and Legal concerns  Effective interventions vs Trial Goals  A way forward?

3. National prevalence of HIV by sex and age in 2002 : Young Women at Risk Note: Log-normal curves were fitted to data collected from the Nelson Mandela / HSRC study of HIV/AIDS

4. Age and gender distribution of HIV infection among 15–24 year olds in South Africa 2003: Source: Pettifora AE, Reesa HV, Kleinschmidt I, Steffensond AE, MacPhaila C, Hlongwa-Madikizelaa L, Vermaake K, Padian NS. AIDS 2005, 19:1525–1534

5. Source: Carrara HRO, Abdool Karim Q, Latka MH, Frohlich JA, Makhaye G, Kharsany ABM, Zuma M, Abdool Karim SS. Submitted to JAIDS Specific HIV Prevalence Trends in Women Attending Prenatal Clinics in Rural KwaZulu Natal, 2001-2005

6. High HIV incidence rates by age in Durban & Vulindlela High HIV incidence rates by age in Durban & Vulindlela 7.25 (5.3–9.2) 51.2% 2817Total 4.0 (0–11.8) 29.0 3150+ 6.4 (0.8–12.1) 39.4 14240-49 12.0 (4.5–19.4) 58.1 26030-39 6.5 (1.3–11.6) 60.9 24825-29 8.5 (4.7–12.3) 45.6 42520-24 5.0 (1.9–8.0) 26.4 360<20 Incidence Rate# (95% CI) HIV prevalence (%) N Age group (years) # Rates per 100 person-years from cohorts in 2005 & 2006 Source: CAPRISA Vulindlela Women & AIDS Programme

7. Opportunities from enrolling minors in HIV Prevention Trials  Evaluate efficacy/effectiveness  Assess Acceptability  Determine Safety  Identify adherence issues  Ideal conditions for identifying and resolving potential problems  ? Licensure – HPV Vaccine

8. Context of research in minors  Caution about inclusion  Reluctance by IRBs/ECs, Regulatory Bodies, and Scientists to enrol in biomedical prevention trials  Behavioural context for young people delay onset of sexual debut &/or abstinencedelay onset of sexual debut &/or abstinence Already high HIV prevalence that need to be addressed vs Reliance on untested & restrictive abstinence messagesAlready high HIV prevalence that need to be addressed vs Reliance on untested & restrictive abstinence messages

9. Context – General  Access to care vs research (therapeutic vs preventive)  Ethical Dilemmas not resolvable by definition – define an acceptable approach  Ethics guidance – not cast in granite (dialogue)  Law vs Ethics --- blind adherence to the law? Sex work is illegal – research conducted  Adolescents vs young people - <18 years vs <24 years  Assent vs Consent (UNAIDS Ethics Guidance)  Emancipated minors (CIOMS)

10. UNAIDS Ethics Guidance on inclusion of Children & Adolescents  UNAIDS - children, including infants and adolescents, should be eligible for enrolment in HIV preventive vaccine trials As a matter of equityAs a matter of equity Young adolescents and children are at high risk of HIV infection.Young adolescents and children are at high risk of HIV infection.  No discernment on Adolescent participation with parental consent vs autonomous participation of adolescents

11. CIOMS and Mature Minors  In some jurisdictions, individuals who are below the general age of consent are regarded as "emancipated" or "mature" minors and are authorized to consent without the agreement or even the awareness of their parents or guardians.

12. CIOMS, “Mature Minors” and ECs/IRBs Some studies involve investigation of adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs; other research addresses domestic violence or child abuse. For studies on these topics, ethical review committees may waive parental permission if, for example, parental knowledge of the subject matter may place the adolescents at some risk of questioning or even intimidation by their parents.

13. Enrolling minors in trials – ethical concerns  Vulnerable population Experiential maturityExperiential maturity Physical maturityPhysical maturity Diminished autonomyDiminished autonomy Legal and social challengesLegal and social challenges Confidentiality and Right to PrivacyConfidentiality and Right to Privacy  HIV specific challenges Ability to adopt safer sex practicesAbility to adopt safer sex practices

14. Assent vs Consent: Confidentiality & Privacy  Implications of an HIV-positive test result Negative connotationNegative connotation Stigma &. DiscriminationStigma &. Discrimination Violence and social ostracizationViolence and social ostracization Gender bias and not restricted to minorsGender bias and not restricted to minors  Willingness to participate Will HIV status will be disclosed to the parentsWill HIV status will be disclosed to the parents Obligations of HCWS vs participant right to privacy & confidentialityObligations of HCWS vs participant right to privacy & confidentiality  ? Implications for health seeking behaviours  Respect for an adolescent participant’s autonomy and right to confidentiality Parental consent nullifies obligationParental consent nullifies obligation

15. Legal challenges  Variation between nations  <18 years = minor  Ethical and legal safeguards – protect their interest but also diminish their autonomy  SA – parental consent required for research participation  > minimal risk requires consent from both parents No parents/guardians – cannot participate in researchNo parents/guardians – cannot participate in research Restrictions eliminate participation by minors from child-headed households, absent father households and grandmother headed householdsRestrictions eliminate participation by minors from child-headed households, absent father households and grandmother headed households Moral judgements about sexuality – unlikely that teenagers will seek parental guidance and permission for participation in HIV prevention researchMoral judgements about sexuality – unlikely that teenagers will seek parental guidance and permission for participation in HIV prevention research

16. Counter concerns  Social autonomy for fully informed consent vs skills or competencies for independent decision-making  Limited life experience complicates balancing risks and benefits  Cognitive skills especially for younger adolescents – not fully developed - ? Adequacy for some research related decision-making 

17. Effective interventions  Multiple levels, highly complex nature of HIV epidemic  Biomedical interventions – great promise but do not address fundamental structural drivers  NB of integrating science and society – community partnerships and engagement processes Advocacy and policy supportAdvocacy and policy support Community and civil society participationCommunity and civil society participation Clinical research enterpriseClinical research enterprise AcceptabilityAcceptability Policy and Program developmentPolicy and Program development 

18. Components of the Prevention Science Research Continuum Stage 1 ConceptualStage 2 Experimental Stage 3 Applied Phase 4 Effectiveness Community Ownership Long-term Acceptability Program Implementation Phase 2Phase 3 Conceptual Development Theory/ Biological Plausibility Phase 1 Safety Community Engagement Community Awareness Formative Operations Program Modeling Hypothetical Acceptability Experiential Acceptability Clinical Acceptability Policy Application Advocacy Policy Development MacQueen KM, Cates W. AJPM 2005;28(5)::491-5.

19. Summary  Notwithstanding underlying variability between regions vulnerability of youth is global  Toll on youth globally and adolescent women imperative to protect them from HIV infection  Social, political and economic drivers of risk and vulnerability need to be simultaneously addressed  Several options for addressing challenges – 5 pronged approach  Develop and evaluate effective models for collaborative, participatory and interdisciplinary approaches  Support stakeholders to respond to emerging issues  Enhance efforts at trust building, communication and fair benefits for research communities