Thorny Issues in HIV Vaccine Trials

1
Thorny Issues in HIV Vaccine Trials

• Saul Walker
• Policy Advisor
• IAVI

2
Thorny Issues?

• Vaccine positivity (including insurance)
• Clades
• Partial efficacy and end-points
• Cohort selection
• Phase 2b or not Phase 2b
• Placebo selection
• Standards of Care for trial participants in
  developing countries

3
Vaccine positivity

• Vaccines often intended to induce antibodies
• Standard HIV tests may show ve for vaccine
  induced response
• Possible to determine true and vaccine positivity
  through selective tests, such as PCR
• Volunteers provided with information and
  directions for future testing
• Insurance
• ABI recognised issue of vaccine positivity
• Assumptions that volunteers are high risk

4
Clades

• Genetic variability in HIV produced numerous
  clades

5
Clades
6
Clades

• Genetic variability in HIV produced numerous
  clades
• Variability challenging for vaccine design but
  dont know how important clade issue is
• Animal data showing cross reactivity for a number
  of candidates
• Only clinical data will be conclusive
• Potential for multi-clade vaccines
• VRC has an ABC product
• Some parts of virus relatively well conserved
• Broad protection a key objective

7
Efficacy

• Types of Immunity
• Sterilising Immunity (Vs) protection from
  infection
• Disease mitigation (Vp) infection but delays or
  prevention of disease progression
• Reduced Infectiveness (Vi) lower VL leading to
  reduced transmission
• End points
• For Vp focus has been on viral set point and/or
  time to treatment
• Vi more difficult to design ethical trial
• Limited Efficacy
• Some of the people all of the time or all of the
  people some of the time
• Efficacy and Effectiveness potential for
  behavioral reversals

8
Cohort Selection

• Adolescents
• A key group that could benefit from a vaccine
• Consent issues and parental sensitivities
• Discordant couples
• Treatment for positive partner?
• Possible European cohorts
• Vulnerable groups
• IDUs, sex workers, MSMs . Service men/women etc
• Adding to existing stigma

9
Phase 2b Trials

• Need to accelerate development and time to field
  while managing investment risks
• Novel trial designs and strategies
• Phase 2b - Proof of concept
• Shorter trial designed to show efficacy gt 0
• Expand into Phase 3 trial for license
• Reduces initial trial costs but can increase
  total time
• Reduces manufacturing investment risks
• Designs that expand into Phase 3

10
Placebo Selection

• Compare gold standard with gold standard
  vaccine
• Under trial conditions, gold standard can
  dramatically reduce incidence
• Availability of limited efficacy vaccines could
  make trials impractical
• Phase 2b to Phase III transition?
• Availability of new prevention options, such as
  microbicides

11
Standards of Care in Developing Countries

• Trial participants package of care including
  primary care and HIV prevention
• Treatment beyond trial not an ethical obligation
  for prevention trials
• morally praiseworthy
• Emerging consensus of how not if
• Practical issues who, when, how long, ensuring
  provision, cost
• Agreement on shared responsibilities
• Sustainability
• Trial/community disparities

12
Standards of Care in Developing Countries

• Consultation essential
• Policy development evolved in discussion with
  WHO-UNAIDS, other sponsors, researchers and NGOs
• IAVI undertaken consultations in Uganda and India
  consultations

13
IAVI SOC Policy - Commitments

• Ongoing consultation on detail and implementation
• Support primary healthcare and HIV prevention
  services to an agreed standard for trial
  participants for the duration of the trial
• Support access to treatment, care and support,
  including ART when recommended by treatment
  guidelines, for participants who become HIV
  infected during a trial
• Initial commitment of 5ys ART after start of
  treatment recommended
• Funding for therapy through an Escrow Account or
  appropriate national scheme.
• Treatment guidelines will be agreed with country
  stakeholders before trial initiation with WHO
  guidelines providing a baseline
• IAVI will ensure referral to local support
  services for volunteers who are HIV-infected and
  who are screened out before enrolment

unless sufficiently covered under and existing
national programme
14
IAVI SOC Commitments

• IAVI will work actively with country and
  international stakeholders to support
  opportunities for trial related investments to
  provide benefit to communities in which trials
  take place
• Capacity building
• Link trial activities with local HIV/AIDS
  programmes and health services
• IAVI will work with country and international
  stakeholders to support
• Sustained provision of treatment, care and
  support for trial participants who have become
  HIV infected during a trial
• Opportunities to build on trial related
  investments to provide sustained community health
  benefits