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Prevention Sciences Program 
Present & Future 
Sheryl Zwerski, MSN, CRN 
November 5, 2014
Overview 
• Orientation to PSP 
• Program Objectives 
• Major Projects/Programs 
– Contracts 
– Programs 
– Networks 
• Future Scientific Directions 
DAIDS/PSP
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 
Maternal, Adolescent, & 
Pediatric Research 
Branch 
Devasena Gnanashanmugam 
Chief 
Betsy Smith 
Patrick Jean-Philipe 
Judi Miller 
Ellen O’Gara 
Renee Browning 
November 10, 2014 *Contractor
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
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
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
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
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
Contract Resources for Microbicides and Prevention 
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 
DAIDS/PSP
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
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
Preclinical Programs 
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 
DAIDS/PSP
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
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
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
IMPAACT Clinical 
Trial Network 
DAIDS/PSP
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
HIV Prevention 
Trials Network 
(HPTN) 
DAIDS/PSP
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
Microbicide Trials 
Network 
(MTN) 
DAIDS/PSP
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).
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
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
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
The Future for Prevention Sciences 
• 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 
Program
Prevention Sciences Program Pipeline 
Discovery Preclinical 
IIMMPPAAAACCTT NNeettwwoorrkk 
Prevention Trials 
Network 
Microbicide Trials 
Network 
Preclinical I Pre- 
II III 
Studies 
Phase I 
(Critical Path) 
Studies 
Virology Clinical Studies 
MP3-III (PA) 
Comprehensive Resources for Topical Microbicides 
and Biomedical Prevention (CRMP) 
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) 
IKNOW (PA)
Thank You for 
Listening! 
Questions? 
DAIDS/PSP

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Prevention Sciences Program: Present and Future

  • 1. Prevention Sciences Program Present & Future Sheryl Zwerski, MSN, CRN November 5, 2014
  • 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 Maternal, Adolescent, & Pediatric Research Branch Devasena Gnanashanmugam Chief Betsy Smith Patrick Jean-Philipe Judi Miller Ellen O’Gara Renee Browning November 10, 2014 *Contractor
  • 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 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 DAIDS/PSP
  • 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. Preclinical Programs 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 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. The Future for Prevention Sciences • 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 Program
  • 26. Prevention Sciences Program Pipeline Discovery Preclinical IIMMPPAAAACCTT NNeettwwoorrkk Prevention Trials Network Microbicide Trials Network Preclinical I Pre- II III Studies Phase I (Critical Path) Studies Virology Clinical Studies MP3-III (PA) Comprehensive Resources for Topical Microbicides and Biomedical Prevention (CRMP) 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) IKNOW (PA)
  • 27. Thank You for Listening! Questions? DAIDS/PSP