Sheryl Zwerski, MSN, CRN

1. Sheryl Zwerski, MSN, CRN
November 5, 2014
Prevention Sciences Program
Present & Future

2. Overview
• Orientation to PSP
• Program Objectives
• Major Projects/Programs
– Contracts
– Programs
– Networks
• Future Scientific Directions
DAIDS/PSP

3. Office of the Director
Sheryl Zwerski, Acting Director
Fulvia Veronese, Assistant Director
Cherlynn Mathias, Program Grants Coordinator
A J Reece, Program Assistant
Millicent Moye, Program Assistant
John Wroblewski, Program Specialist
Preclinical Microbicide
and Prevention
Research Branch
Jim Turpin, Chief
James Cummins
Leslie Marshall
Anabel Lowry
Kristen Porter
Hans Spiegel
Mike Gilbreath
Clinical Microbicide
Research Branch
Roberta Black, Chief
Jeanna Piper, Deputy
Lydia Soto-Torres
Grace Chow
Lester Freeman
Naana Cleland
Prevention Sciences Program
Clinical Prevention
Research Branch
David Burns, Chief
Vanessa Elharrar, Deputy
Wairimu Chege
Alain Kouda
Elizabeth Flanagan
Usha Sharma
Annie Waterman
July 24, 2015 *Contractor
Maternal, Adolescent, &
Pediatric Research
Branch
Devasena Gnanashanmugam
Chief
Betsy Smith
Patrick Jean-Philipe
Judi Miller
Ellen O’Gara
Renee Browning

4. PSP Objectives
1.) Deliver prevention tools that can reduce HIV
incidence in populations at risk by:
– Creating and sustaining a pipeline for non-vaccine
HIV prevention products using rational development
algorithms with clear go/no go criteria focused on:
• Sustained delivery methods
• Combination products (combination ARVs and
MPTs)
DAIDS/PSP

5. PSP Objectives
• Supporting clinical product development activities
that include appropriate safety and efficacy testing as
well as integrated PK/PD assessments and advance
HIV prevention candidates to licensure, specifically:
–Topical microbicides (vaginal and rectal)
–Systemic pre-exposure prophylaxis (PrEP)
–Other novel prevention products (including
biological, drugs and devices)
DAIDS/PSP

6. PSP Objectives
• Supporting efforts to improve treatment as
prevention by optimizing the testing, linkage to care
and treatment cascade.
2.) Support efforts to optimize HIV treatment for
pregnant women, infants, children, and adolescents.
DAIDS/PSP

7. PSP Objectives
3.) Contribute significantly to the advancement of
DAIDS cure agenda in infants and children.
4.) Supports efforts to transform the diagnosis,
prevention, and treatment of TB and other co-
infections of importance in the maternal/child
population.
DAIDS/PSP

8. PSP Objectives
5.) Partner with our NIMH and NIDA colleagues in both the clinical
and the preclinical arenas to incorporate behavioral research:
• ADHERENCE
• Accurate assessment of likelihood of intervention uptake
• Assessment of risk for ppts and providers
• Effective coping with stigma
• Substance use’s effects on all of the above
– Development of strategies to effectively engage this
population
DAIDS/PSP

9. Contract Resources for Microbicides and Prevention
DAIDS/PSP
3 Current Work Scopes
•Gap-Filling
•Development Planning
•Best Practice Working Groups (BPWG)
Accomplishments:
•Collaborating with Merck with IND enabling preclinical toxicity studies for
combination vaginal ring
•Supported MTN 013 with extractable and leachable studies
•Optimizing biophysical properties of single and combo ARV ring for IPM
•Performed multiple rabbit vaginal and rectal irritation studies to enable
Phase I studies
Future:
•RFP in development

10. Preclinical Programs
Mucosal Environment and HIV Prevention (MEHP)
Objective: Enhancement of HIV microbicide, PrEP and MPT
prevention strategy efficacy and safety by understanding their
interaction with the male and female genital and GI mucosa and
optimizing that interaction to better promote inhibition of HIV
transmission and acquisition
Accomplishments:
• Robust responses with varied topics of exploration
Future:
• Current round of funding should assure robust investigations
on the topic and consideration of future iterations is underway
DAIDS/PSP

11. Preclinical Programs
Preclinical Innovation Program (PIP)
Objective: Preclinical discovery and testing of single and
combination drug strategies and promotion of the
integration of new safety, efficacy and adherence
technologies into the prevention pipeline.
Accomplishments:
• Robust response which included truly innovative delivery
systems and validation of needed safety models
Future:
• Under consideration given fiscal constraints and
program needs
DAIDS/PSP

12. Integrated Preclinical/Clinical Program (IPCP)
Objective: Stimulate a strong, diverse base in preclinical
discovery and development of new topical microbicides and
biomedical prevention for vaginal, rectal, penile and
oral/injectable use and support translation from preclinical to pre-
Phase 1 clinical studies
Accomplishments
• CROI 2014 presentation of first in human film study
• First testing of rectal specific TFV gel
• Begun pre-phase I study of TDF IVR with novel ring
platform
Future
• Future program needs being considered
Preclinical Programs
DAIDS/PSP

13. Preclinical Programs
Sustained Release of Antivirals for Treatment and Prevention
(Collaboration between PSP and TRP)
Objective: Build a pipeline of long acting release formulations for non-
vaccine biomedical prevention (microbicide, PrEP) and therapeutic
candidates with a goal of a minimum of once a month dosing
Accomplishments:
• PAR and FOA released earlier in 2014
Future:
• Consideration underway for best way to stimulate the area for
prevention
DAIDS/PSP

14. Clinical Programs
Methods for Prevention Packages Program (MP3)
Objective: Increase collaborations between behavioral and
biomedical clinical scientists, modelers, and clinical trialists to
facilitate the design and testing of combination HIV prevention
interventions (prevention packages)
Accomplishments:
• First 6 projects are completing
• Packages must be population and region/locality specific
• Cost effectiveness of package is epidemic context
dependent
Future:
• Received robust response to recent PAs
DAIDS/PSP

15. Clinical Programs
Increased Knowledge and Innovative Strategies to Reduce HIV Incidence
(iKnow)
Objective: Promote innovative research to improve our ability to identify
populations that are both at high risk of HIV-1 infection and have a high
proportion of persons that are unaware of their HIV status, and to
successfully link them to HIV testing, effective prevention interventions, and,
if HIV-positive, care and treatment
Accomplishments:
• PAR released and robust response received
Future:
• Need is well documented, future funding uncertain
DAIDS/PSP

16. IMPAACT Clinical
Trial Network
DAIDS/PSP

17. IMPAACT Mission
• Areas of focus for pregnant women and
children
– HIV Treatment
– HIV Prevention
– HIV Cure
– HIV Co-morbidities & Complications
– TB diagnosis, treatment, and prevention

18. HIV Prevention
Trials Network
(HPTN)
DAIDS/PSP

19. HPTN Mission
• Discover and develop new and innovative
research strategies to reduce the acquisition
and transmission of HIV.
– Develops systemic PrEP, including long-acting
products
– Does not develop vaccines or microbicides, but
integrates once efficacy data available

20. Microbicide Trials
Network
(MTN)
DAIDS/PSP

21. MTN Mission
• Bring together investigators, community, and industry partners to
work on the development and rigorous evaluation of promising
microbicides – products applied inside the vagina or rectum that
are intended to prevent the sexual transmission of HIV.
• Collect the kind of data regulatory agencies require for determining
whether to approve a product for widespread use.
• Behavioral and social science is embedded within each study to gain
understanding of the needs and desires of different high-risk
groups.
• Include populations considered among those at highest risk,
including women in Sub-Saharan Africa, adolescents, pregnant and
breastfeeding women, transgender women and men who have sex
with men (MSM).

22. The Future for Prevention
Sciences Program
• Build a pipeline of sustained release products for prevention
– Topical micobicides
– PrEP
• Increase contextual awareness
– Micro & Macro environments
• Mucosal level
• Population level
DAIDS/PSP

23. The Future for Prevention
Sciences Program
• Integrate behavior into all phases of study, including
preclinical
– Understand what women (and men) want
• Lessons learned must remain at the forefront of all
future work
• Explore innovative trial methodologies/evidence required for
moving prevention products and packages forward
DAIDS/PSP

24. The Future for Prevention
Sciences Program
• Sharpen focus on the Testing & Treatment Cascade
– Improve testing strategies for most at risk
– Improve linkage and engagement in care
• Support testing of integrated prevention strategy packages
that are appropriate, acceptable and cost effective for target
populations
• Increase efforts to deliver strategies that can be scaled up to
reduce incidence in adolescents
– Young MSM globally
– Females in SSA
DAIDS/PSP

25. • Focus on achieving appropriate safety and PK/PD of new ARVs
for pregnant women, children and adolescents
– Optimize first line treatment from infancy through adolescence
• Partner with other DAIDS programs, ICs, and agencies to
explore all reasonable efforts to explore infant cure
• Partner with other DAIDS programs, NIAID divisions, ICs and
outside donors to improve TB diagnosis, prevention, and
treatment for pregnant women and children
DAIDS/PSP
The Future for Prevention Sciences
Program

26. Discovery Preclinical
Virology Clinical Studies
I II IIIPreclinical
Studies
(Critical Path)
Pre-
Phase I
Studies
Comprehensive Resources for Topical Microbicides
and Biomedical Prevention (CRMP)
Microbicide Trials
Network
Prevention Trials
Network
Mucosal Environment
and HIV Prevention
(MEHP II)
Prevention Innovation
Program (PIP)
Sustained Release Program for non-Vaccine
Biomedical Prevention and Therapeutics
(SRP-nBPT)
Integrated Preclinical Clinical Program
for Microbicides and Biomedical
Prevention (IPCP-MBP)
Prevention Sciences Program Pipeline
IKNOW (PA)
MP3-III (PA)
IMPAACT NetworkIMPAACT Network

27. Thank You for
Listening!
Questions?
DAIDS/PSP