CHVI Team Grant in HIV Vaccine Discovery and Social Research:
Barriers to engaging young people in HIV vaccine trials in a priority setting
“Developing a multi-disciplinary strategy to examine HIV risk
and clinical outcomes in South African adolescents”
Mark A. Brockman (Simon Fraser University, Canada)
Glenda Gray (Perinatal HIV Research Unit, Soweto, South Africa)
Thumbi Ndung’u (Univ of KwaZulu-Natal, South Africa)
Angela Kaida (Simon Fraser University, Canada)
Jeremy Snyder (Simon Fraser University, Canada)
Engaging the World
HIV in South Africa
• South Africa remains at the center of the HIV/AIDS epidemic
• ~5.6 million individuals are currently living with HIV
• HIV prevalence rate in adults (15-49 yrs) is 17.3% (national)
• Sentinel surveys of pregnant women in Gauteng (Soweto) and
KwaZulu-Natal (Durban) indicate prevalence rates >40%
• HIV prevalence in adolescents aged 15-19 yrs (>15%) is among the
highest in the world
(UNAIDS, 2011)
Adolescents and Young Adults (AYA)
• ~50% of new HIV infections in South Africa occurs among
individuals aged 15-24 yrs
• Young women are at particular risk:
• ~30% give birth before the age of 20 yrs
• Often in relationships with older male partners
• ~15% of South African females aged 15-24 yrs are living with HIV
• Adolescents and young adults (AYA) (aged 15-24) are therefore a
key target population for HIV vaccine and prevention efforts
• Implementing effective approaches for this age group is likely to
require detailed sociological and biomedical understanding of local
epidemics, as well as novel engagement and retention strategies
Problem Statement
Risk of HIV acquisition, and clinical outcome, in AYA is likely to be
influenced by a complex array of social, behavioural, and
biological determinants.
However, a lack of high quality, population-based, linked
social/behavioural, clinical, and biomedical datasets for high-risk
AYA populations have hampered efforts to identify these factors
in detail. Such data is likely to be critical to the future success of
HIV vaccine studies that target this important population.
Goal and Objectives
Goal: To implement cohort-based strategies to examine barriers and
knowledge gaps that hinder engagement of AYA in HIV vaccine research
and prevention trials.
Our multi-disciplinary team of social, ethical, clinical, and biomedical
researchers will address the following four objectives:
A. Infrastructure and capacity: Develop prospective cohorts of high-risk South
African adolescents to support multi-disciplinary HIV prevention research.
B. Ethics and community: Develop culturally appropriate strategies to obtain
youth consent and understand community attitudes towards youth
participation in HIV prevention research trials.
C. Social science: Understand social/behavioural determinants of HIV risk in AYA
and identify unique barriers to participation in HIV vaccine trials.
D. Biomedical science: Identify biological factors associated with HIV risk in AYA
and examine the influence of host and viral genetics, biology, and
immunology on the natural infection course in youth.
Our Team: Cohorts and Infrastructure
Leads: Glenda Gray (PHRU) and Thumbi Ndung’u (UKZN)
Members: Mammekwa Mokgoro and Manjeetha Jaggernath
(UKZN);
Fatima Laher, Erica Lazarus, and Sakhile Mhlongo (PHRU)
Programme Aim #1
• To develop prospective cohorts of high-risk South African AYA with
enhanced capacity to undertake multi-disciplinary research.
Target enrolment (400 AYA, ages 16-24)
• 300 HIV-negative sexually active AYA (150 Soweto, 150 Durban)
• 100 HIV-positive sexually active AYA (50 Soweto, 50 Durban)
Intended follow-up: 2 years
• Referrals for male circumcision, family planning, special counselling
• Baseline and bi-annual HIV/STI testing, surveys, and counselling
• More frequent follow-up of HIV+ and HIV incident cases
• Nested short-term biomedical research studies (~30 days)
Collect linked social/behavioural, clinical, and biomedical data for participants
Our Team: Ethics and Community
Leads: Jeremy Snyder (SFU) and Cathy Slack (UKZN)
Members: Busiswe Nkala (PHRU); Maud Mthembu (UKZN);
Anita
Ho (UBC)
Programme Aims #2 and #3
• To develop culturally and ethically appropriate strategies for obtaining
informed consent of adolescents and young adults.
• To assess stakeholder concerns associated with enrolling youth in HIV
research and barriers to delivering future HIV vaccines to adolescents.
•
•
•
•
Stakeholder meetings in the community (parents, schools, etc)
Informed consent, parental notification, confidentiality
Mucosal sampling; host genetics/genomics
Regulatory issues, REBs
Our Team: Social and Behavioural Science
Leads: Angela Kaida (SFU) and Glenda Gray (PHRU)
Members: Janan Dietrich (PHRU); Mammekwa Mokgoro and
Maud Mthembu (UKZN); David Bangsberg (MGH); Robert Hogg
and Cari Miller (SFU)
Programme Aims #4 and #5
• To understand complex social, behavioural, and cultural factors
associated with risk of HIV acquisition among AYA in South Africa.
• To assess social and cultural barriers preventing participation by South
African AYA in HIV prevention research and vaccine trials.
•
•
•
•
Bi-annual surveys and interviews for mixed-methods data collection
Determine predictors of retention success
Identify preferred communication methods
Validate measures of HIV prevention knowledge and counselling
Our Team: Biomedical Science
Leads: Mark Brockman (SFU) and Thumbi Ndung’u (UKZN)
Members: Glenda Gray, Fatima Laher (PHRU); Lynn Morris,
Caroline Tiemessen (NICD); Tom Hope (NU); Jo-Anne Passmore
(UCT); David Knipe (HMS); Richard Harrigan, Art Poon (BC CfE);
Zabrina Brumme, Masa Niikura, Ralph Pantophlet (SFU)
Programme Aims #6, #7, and #8
• To examine the prevalence of non-HIV pathogens and consequence on
mucosal immune activity in HIV-negative South African AYA.
• To identify host and viral genetic factors associated with risk of HIV
acquisition and early disease course.
• To evaluate the contribution of innate and adaptive host immune
factors on HIV acquisition and early disease course.
Activities and Challenges
• Progress and Current Activities:
• Team meeting held in Durban (June, 2012)
• Discussed and prioritized research aims
• Sub-contracts/funding agreements have been signed with all sites
• Completing Ethics protocol for submission at PHRU (due: Feb 1st)
• Anticipated first enrollment date June 1st, 2013
• Preparing Ethics application materials at UKZN (Spring submission)
• Challenges
• “Economy”: closure of prior cohorts (funded through other
programs) required us to start from scratch
• Delays due to administration of invoicing and “indirect” costs to
South African sites
Anticipated Outcomes
• Better stakeholder knowledge and community interactions
• Improved understanding of how HIV risk behaviours may change
over time among South African AYAs
• Potential social/behavioural differences between sites
• Strategies to improve recruitment and retention of AYA in trials
• Baseline data for mucosal and peripheral inflammation in AYA
• Potential genetic, co-infection, and/or behavioural factors
• Impact on HIV risk
• Identification of linkages between behaviour and biology
Thank you!
Angela Kaida, Jeremy Snyder, Zabrina Brumme, Robert
Hogg, Masahiro Niikura, Ralph Pantophlet, Laura Cotton
Engaging the World
Thumbi Ndung’u, Manjeetha Jaggarnath, Mammekwa
Mokgoro
Glenda Gray, Fatima Laher, Janan Dietrich, Sakhile
Mhlongo, Busiswe Nkala
Lynn Morris, Caroline Tiemessen
HIV negative at entry (n=300):
(Entry)
Counseling
Survey
Blood Panel
HIV Rapid Test
PBMC/Plasma
STI testing
X
X
X
X
X
X
(6m)
(12m)
(18m) ++
(X)
X
X
(X)
X
X
(X)
X
X
(X)
X
(X)
X
X
X
(X)
X
X
REFERRALS FOR:
• Male circumcision
• Special counseling/family planning
NESTED RESEARCH PROJECTS:
• Baseline STI prevalence
• Mucosal inflammation
• Immune response to other infections/vaccines
X
HIV Rapid Test Positive
HIV Early Cohort
HIV + at entry (Chronic cohort) (n=100):
(Entry)
Counseling
Survey
Blood Panel
PBMC/Plasma
CD4/pVL
STI serology
X
X
X
X
X
X
(6m)
(12m)
X
X
X
X
X
X
X
X
X
X
X
X
(X)
(18m) ++
X
X
X
X
X
REFERRALS FOR:
• ARVs and co-infections
• Special counseling/family planning
NESTED RESEARCH PROJECTS:
• Baseline STI prevalence in HIV+ vs Negative
• Estimated date of infection (viral diversity)
• HIV diversity; plasma vs. semen (men) or CVL (women)
• Molecular epidemiology of subtype C
• Inflammation (CVL)
• Tissue biology/immunology
• Mucosal antibodies
• Viral fitness
HIV Rapid Test + (Incident cases; n=5/yr?):
HIV Rapid Test
Counseling
Survey
PBMC/Plasma
STI (?)
(+) (1-2-3m)
(6m)
X
X X X X
X
X
X X X X
X
X
X
X
X
(12m)
X
X
X
REFERRALS FOR:
• ARVs and co-infections
• Special counseling/family planning
NESTED RESEARCH PROJECTS:
• Estimated date of infection (viral diversity)
• Genetics/fitness of transmitted virus (vs. partner?)
• Impact of existing inflammation/STIs
• Host genetics/genomics (HLA, KIR, etc)
• Early viral evolution and host immunity
X
X
X
X
(18m) ++
X
X
X
X
X
X