1. José Bauermeister PhD, MPH University of Pennsylvania MTN BRWG Member
Building and testing rectal microbicide products: Creating a new era of RM research and development
José Bauermeister PhD, MPH
University of Pennsylvania
MTN BRWG Member

2. From hypothetical to reality
Approximating Real-Life Behaviors within the Procedures of a Clinical Trial Study

3. Modality Scorecard
Liu Annual MTN Meeting

4. Choice matters…
PrEP may not be accessible, available or desired among population segments.
Adherence challenges
Access & Cost
Topical prophylaxis may have buy-in among vulnerable populations who experience risk seasonally.

5. Research within Clinical Trial Models
Behavioral assessments are often interwoven within RM safety studies.
Expectation that behavioral adherence strategies will be effective.
Plug-and-Play Interventions within Biomedical Trials
Different products require different strategies

6. What we have asked…. Awareness Use/Adherence Acceptability
Do they know about the product?
Use/Adherence
Did they use the product?
Acceptability
What predicts product use and intention?
Non-Use Predictors
What predicts non-use?

7. Cherchez Le Creneau Traditional Approach Positioning Approach
Product is Developed in Isolation
Product is Given to Customers
Ignore competition
Highlight benefits
Expect high adoption and adherence
Positioning Approach
Understand consumers’ values
Product is developed with consumer in mind
Understand competition
Relate product to existing brands
Retie users’ experiences with other products to our product.

8. Lin AH, Breger TL, Barnhart M, Kim A, Vangsgaard C, Harris E
Lin AH, Breger TL, Barnhart M, Kim A, Vangsgaard C, Harris E. Learning from the private sector: towards a keener understanding of the end-user for microbicide introduction planning. J Int AIDS Soc. 2014;17(3(Suppl 2). doi: /IAS

9. Gel-based RM
Rectal Microbicide R&D has prioritized gel-based formulations.
Gel often noted as preferred formulation method by participants, yet current delivery approach has challenges.

10. MTN-026
MTN-026/IPM 038 is the first clinical trial to collect safety and pharmacokinetic data on the rectal application of dapivirine gel (0.05%) in a cohort of HIV-uninfected adults.
Behavioral Data:
User acceptability of the product
User-centered suggestions for product design and delivery
Satisfaction with the clinical trial experience
Suggestions to improve the trials from a user perspective

11. MTN-037
MTN-037 is a Phase 1, open label, sequential dose/VET designed to evaluate the safety and PK of PC-1005 (MIV-150/Zinc Acetate/Carrageenan gel) when administered rectally in men. 
Different Volumes :
Acceptability & Tolerability of the product
User-centered suggestions for product design and delivery
Satisfaction with the clinical trial experience
Suggestions to improve the trials from a user perspective

12. Modality & Delivery Matters….
Carballo-Dieguez et al., AIDS & Behavior
Bauermeister et al., AIDS Ed. & Prev.

13. MTN-033
MTN-033/IPM 044 is one of the first clinical trials involving the rectal application of dapivirine gel (0.05%) in a cohort of HIV-uninfected adults.
Assess study gel safety and acceptability, including comparison between Applicator and Self-Administration:
User perceptibility
Existing product use and satisfaction/needs
User-centered suggestions for product design
Experiences with the direct observation dosage method

14. Beyond gel: Diverse modalities…
MSM/TW often report using other rectal products before/after sex.
Diverse modalities may accommodate different social/structural circumstances.
Different segments of the population may prefer some modalities over others.

15. Preferred Modality may vary…
All cities (N=128)
Lima (N=32)
Iquitos (N=31)
Guayaquil (N=33)
Rio (N=32)
Cost ($)
Effect. (%)
Side Effects
Frequency of use
Form.
Dose (ml)
Rx or OTC 1
87.30 (23.96)
83.06 (26.31)
83.06 (26.92)
92.19 (19.51)
90.83 (20.22)
.30 80
None
Before sex
Gel 15 Rx 2
60.77 (33.74)
65.83 (33.40)
62.90 (33.46)
50.00 (34.78)
53.33 (35.19) 5
Some 35
OTC 3
58.54 (34.60)
54.03 (33.60)
41.13 (34.49)
60.94 (33.56)
59.48 (34.34)
Daily
Liquid
Consumer Psychology

16. Rectal Douching Before RAI After RAI
Desire to maintain personal hygiene
Request by sexual partner
Douching enhances pleasure
Friends discussed douching before sex
Desire to prepare/get excited for RAI
After RAI
Protection from STI’s
Desire to maintain personal hygiene
Desire to transition from sex
Request by sexual partner
Douching enhances pleasure
Friends discussed douching after sex

17. Insert/Suppository
Limited data on acceptability, tolerability and adherence of suppository vs. insert modality.
Carballo-Dieguez (2008) found that MSM preferred gel microbicides over a suppository.
However, the suppository used was larger than would be needed for RM delivery.
Studies are needed to assess acceptability of a smaller/differently shaped and formulated.

18. MTN-039 Safety and PK Study of TDF and EVG Administered Rectally
Inserts:
User acceptability of the product
User-centered suggestions for product design and delivery
Satisfaction with the clinical trial experience
Suggestions to improve the trials from a user perspective

19. MTN 035
First study to systematically examine the acceptability, tolerability and adherence of three placebo formulations in a sample of young MSM/TP in 5 countries.
Describe usage patterns and the correlates linked to trajectories of use.
Compare/contrast modalities based on product characteristics and participants’ characteristics and contexts.
Assess modality acceptability and tolerability, including best practices learned from participants’ experiences, as MTN explores formulations.

20. Washout period (~1 week)
MTN 035
Sequence N
Period 1
(4 weeks)
Washout period (~1 week)
Period 2
Period 3 A 35
Rectal insert --
Rectal douche
Rectal suppository B C D E F

21. Flipping the script… Traditional Research Awareness Tolerability
Acceptability
Adherence
Sustainability
Design-driven Research
How can we understand participants’ contexts better?
How do we get them to desire our product?
What makes people keep wanting to use our product?
How do we make a product that is easy and vital to way of life?

22. The way forward!

23. Acknowledgements
The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. The content is solely the responsibility of the author and does not necessarily represent the official views of funding agencies.