1. Next PrEP: Insights from users
NEXT WAVE OF PREVENTION OPTIONS
Next PrEP: Insights from users
Ariane van der Straten and Alexandra Minnis
Women’s Global Health Imperative
RTI International – San Francisco, CA USA
Satellite Session:
Sunday, 23 July 2017, 14:45-16:45

2. Choice is an effective model in family planning

3. (Hypothetical) end-user product preferences
Preferred attributes:
Efficacy/safety
Safe/no side effects
Reliable
Reversible; retrievable
Product:
Long(er)-acting
Dosing: easy/painless
Non-invasive
Use:
Familiar
Discreet
Female-controlled
Sex: Non-interference
VOICE-D (N=68)
ASPIRE (N=71)
Major limitation: variable familiarity with different delivery forms, disinterest for formulation that are unknown.
Preference: minimize use burden and simplify administration.
Mix of formulations that participants had experience with and those that were hypothetical.
One of the limitation is that women seem to be fairly uninterested in unfamiliar product -> need to know and understand well how the product works to be interested in it.
KEY
≥50% , ≥ 25% , <25%
Luecke et al., JIAS 2016
van der Straten IAS 2016, APS 2017 forthcoming

4. TRIO Study (2014-2017) Study Sites:
Kisumu, Kenya: N=137 Soshanguve, South Africa: N=140
Eligibility:
HIV-negative
Sexually active
Non-pregnant
Aged years
Microbicide and PrEP naïve

5. Trio: key design features
Attitude/opinion → observable behavior
Partcipant → Co-designer
Rating and preference
baseline
After 1 month of trying product
choice
After randomly trying each product for 1 month
Useage
Use chosen product for 2 months
Opportunity to switch product
We designed Trio so that all products would have its fair chance by having been tried by participants before they chose it.
What we found is that Participants valued being treated and considered as “Co-designers”
We also found (and it was reassuring) that in Trio opinions and behaviors were very correlated, that is what they said they preferred was also what they chose and used

6. Product ratings in TRIO
Injections were the most preferred product.
Rating of all products increased after one month of use.
Greatest increase for the least familiar product: rings.
Product attributes related to the burden of use were most influential on product ratings.
The last bullet is a summary of results from multivariable linear regression where we examined predictors of rating for each product after one month of use.
Minnis, et al., IAS 2017 #WEPEC0940.

7. Product choice differed by country (N=249)
Kenyan women were more likely than South African women to choose tablets or rings compared to injections; & less likely to choose rings compared to tablets.
Choice was not associated with age, marital status, education, AEs or with last product used in the crossover period.
Month 3, N=249
Product chosen to use in the next 2 months of the “use” period.
P-values from multinomial logistic regression model. Model only included site (did not control for other variables)
Tablets (vs Injections)
RRR (95% CI)
Ring (vs Injections)
Ring (vs Tablets)
Kenya (vs South Africa)
2.23** (1.73 – 2.87)
1.52* (1.15 – 2.02)
0.68* (0.49 – 0.96)
van der Straten, et al., IAS 2017 #WEPEC0978.
* p< ** p<0.001

8. iPrevent: 2-stage end-user research study
Goal: To identify aspects of sustained-release long-acting PrEP that are important to male and female youth in Cape Town, South Africa.
Stage 1: 50 in-depth interviews & 6 focus group discussions.
Stage 2: Discrete choice experiment with 800 youth.
Youth engagement central to iPrevent’s approach.
Notes:
IDIs conduted with youth aged who had exited biomedical prevention trials in Cape Town – injectables, rings and tablets.
Stage 2 of the study is now underway – a discrete choice experiment with 800 youth in Cape Town high-density communities/townships. Focus is on understanding attributes that are influential to product preferences for injectable and implantable PrEP product.

9. iPrevent – youth preferences
Injectables and implants favored because of their longer duration, increased discretion and reduced stigma.
Dimensions of “Invisibility” preferred.
Effortless flow through the body for an extended period.
Pain free with no side effects.
Products that could go unnoticed and not be felt by friends, family, partners or community-members.
Systemic Absorption (“it stays in the body”) resonated with youth.
“I want it to be inserted but to be unseen that it is in you… Not to be something that will be associated with sewing (stitches)… Yes, leave me with no pains and not to be felt” (IDI, female, ring-experienced)
Montomery, et al., IAS 2017 and Atujuna, et al. IAS 2017.

10. End-user research extension of iPrevent & TIP
Purpose: engage youth and health providers in providing input on the design of implant for PrEP
FGD with women aged 18-24
Implant and injectable naïve (4 FGD)
Placebo PrEP injectable experienced (2 FGD)
Implant experienced (4 FGD)
FGD with men aged 18-24
Implant naïve (4 FGD)
IDI with health care providers (30 IDI)
Soshanguve
Cape Town
“End-user” includes both the person who receives an implant AND the health care provider who administers it.
Two qualitative methods used:
--Focus group discussions (FGDs) Groups: men, women (implant-experienced), women (never used implants); women (PrEP injectable experienced – only in Soshanguve)
-- In-depth interviews (IDIs): Health care providers with experience inserting contraceptive implants
Work was amended into two clinical research studies: iPrevent Study at Desmond Tutu HIV Foundation in Cape Town and TRIO at the Setshaba Research Centre in Soshanguve

11. FGD voting activity results (n=86)
“I don’t like to eat any pills so that’s why I’m excited.”
– Implant Naïve Female, Cape Town
58% of participants report feeling excited about the implant and were most excited about the long-lasting nature, discreetness, protection in situations when one doesn’t or cannot use condoms, not needing to take pills or the related stigma of taking pills, and for the impact it will have on HIV prevalence in their community.
77% of participants would rather have a larger device that lasts six months rather than a smaller device that lasts three months. Those who voted for the six month large device discussed wanting to minimize the burden of clinic time including travel and visits, reduce number of painful insertions they receive, and eliminate potential adherence issues.
58% of participated would rather have two devices for 12 months rather than one device for six months. Participants described the same positive attributes and dislikes as before in addition to concerns about two devices for 12 months such as getting too much drug, increased side effects, more painful insertion.
84% of participants voted for a flexible implant and discussed not wanting others or themselves to be able to feel it, fear of a stiff device being robbed, a less painful insertion process, and perceived it as having fewer side effects and being more effective. However, other participants wanted their partner to be able to feel it and liked that a stiff device would allow for them to monitor the dissolving process.
92% of participants preferred the dissolvable device to a removable one. Participants liked be able to avoid a experience painful removal and scarring, described there not enough qualified providers to remove the implant, and less of a clinic burden.
“I chose the flexible one because I want it to be my own privacy. I don’t want someone else to see it.”
–Implant Naïve Female, Soshanguve

12. Health care providers: preliminary results (n=8)
Overall positive reactions toward implant device (reduced clinic burden)
Long-lasting duration preferred
Especially excited about biodegradability
Liked flexibility of device, but cautioned some palpability is needed
Young people want a flexible device; HCP want medium stiffness
HCP suggestion: make one end of device stiff?
Remaining questions to focus on during HCP interviews:
Community perception of “plastic” in medical device
Trocar preferences
Implant robbery stories (Cape Town)
Best setting for service delivery?
PATH ongoing heuristic evaluations about the applicator system
8 / 30 IDIs completed
Overall positive toward device for HIV prevention to reduce clinic burden
Long-lasting duration preferred
Especially excited about biodegradability (HCP confirmed that removal is much more challenging than insertion, and many are not trained to do removal).
Liked flexibility of device, but cautioned palpability is needed to locate device for removals
Mechanical stiffness: young people want a more flexible device (more discreet), while most HCP want a more medium-stiffness device (like the extruded tube) to allow for palpation if necessary to remove device
Suggested making one end of device palpable if removal is necessary due to side effects, but keep the majority of the device flexible
Where do preferences of young people vs. HCP differ?
Mechanical stiffness
Very flexible (young people)
Medium stiffness (HCP) : palpability required for removal; feasibility of insertion
Remaining questions to focus on during HCP IDIs
Community perception of “plastic” used in medical inserts
Trocar preferences (Implanon vs. Jadelle vs. other)
Continued probing around implant robbery stories (Cape Town)
Best setting for delivering HIV prevention implants

13. Next PrEP: Value Added to the Field if Successful
Dosage
Form
Minimize Gap:
from Efficacy
to Effectiveness
Minimize User
Burden
Preference*
Low
Systemic
Side Effects
Ease of
Reversibility
Health
system
burden
Protection
Condoms  
Daily oral
tablet
On demand
microbicide ? ?
Vaginal ring
Injectable ?
Implant
Columns 2 and 3 reflect feedback received from youth, young women and providers across all of these studies.
* HYPOTHETICAL OR ACTUAL: Luecke, JIAS 2016, VDS APC 2017; VDS CROI 2017

14. In summary Ask end users opinons. They are the experts
Engage and motivate users as co-designers
Corroborate preference with actual choice and behaviors
Beware: Every body lies!
Voting activities on TFPD “device” attributes
Lab coats given to participants to invite them as community experts and co-designers
CONFIDENTIAL

15. Thank you! Funders Collaborators/Organizations USAID/PEPFAR
Bill & Melinda Gates Foundation
Whitaker International Fellows and Scholars Program (Emily Krogstad)
Collaborators/Organizations
JHU
MWRI/Upitt
PATH
PSI
RTI/RTP
RTI/WGHI
UCSF
DTHF
SRC
IRDO
CONFIDENTIAL

16. extra

17. Notes on key narrative for the presentation
Increasing choice in HIV prevention options is a shared goal among prevention scientists (intro remarks on title slide):
Uptake and sustained adherence to HIV prevention methods is a widely recognized challenge that long-acting injectable and implantable approaches aim to overcome
Recognition that users are diverse and have varied needs and contexts (social/family/partnerships).
These are dynamic and change over the life course. Ideal method mix would offer choices so that individuals can chose the method that is best for them and their circumstances at a given point in time.
Choice is the model for family planning - evidence that diverse contraceptive method mix increases uptake and use (Slide 2).
Recognition that choice of methods offers women/couples opportunity to align method with sexual/reproductive life course.
Strong evidence from many studies that users want longer-acting products – implants and injectables aim to address this need (slides 3- provide evidence from different studies conducted by our team).
Promising approach b/c adherence to daily regiment is difficult for users . LA PrEP offers reduced burden, ease of use, discreteness
Share our data from TRIO, iPrevent and TOP/iPrevent FGDs/HP interviews
TRIO – preferences based on 1-month of use. slides – design; choice slide; ratings after use; attributes tied to user burden most influential to ratings.
iPrevent –Aim 1 interviews? Injection vs. implant? FGDs. Planned DCE – data collection began July 4, 2017.

18. Trio Background and Study Overview
TRIO Study design
Cross-Over Test Period
Usage Period
Choice
Participants randomized to a product use sequence, and used each study product for one month
Participants used their chosen product for 2 months; could choose to switch at month 4
3 months
2 months
Persistence
Switch
Randomized, cross-over study where women tried each of three products for one month; following by choice of product they wanted to use for subsequent 2 months during “usage period.”
Objectives: to assess product preferences and choice during the cross-over period; use and persistence during usage period.