1) Researchers at Zuckerberg San Francisco General Hospital developed a point-of-care urine test that can rapidly and accurately detect tenofovir, the active drug in PrEP, to provide near real-time adherence feedback. 2) Previous studies found drug level feedback alone may not improve adherence, but it can guide targeted adherence counseling interventions delivered as soon as possible for those with low drug levels. 3) The researchers plan to test the urine test combined with brief motivational counseling targeting low adherers in upcoming PrEP studies of young women in Kenya and young men who have sex with men in San Francisco.

1. Zuckerberg San Francisco General
Using Urine Point-of-
Care Tenofovir Testing to
Deliver Targeted PrEP
Adherence Counseling
Interventions
Matt Spinelli, MD MAS
Division of HIV, ID, and Global Medicine
San Francisco General/UCSF

2. Zuckerberg San Francisco General
San Francisco General Hospital
Background: PrEP Adherence Remains a Challenge in
Key Populations
 Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) highly effective in preventing HIV
with adequate adherence1,2
 PrEP adherence a challenge in various settings despite high self-reported adherence: up
to 66-91% with low adherence in some demonstration projects:3,4
- Key groups: Young MSM, Black and Latinx MSM, young African women 3,4,5
1. Grant Lancet ID 2014 2. Hare CROI 2019 3. Hosek J Int AIDS Soc 2016 4. Celum IAS Conference 2019
5. Serota CID 2019

3. Zuckerberg San Francisco General
San Francisco General Hospital
Drop-offs in Adherence are a Marker of Future
Discontinuation Risk
 Most PrEP users in the U.S. PrEP Demo had a clinical visit demonstrating poor recent
adherence (low FTC-TP in DBS) prior to LTFU, and this was associated with future
discontinuation (HR: 7.5; 95% CI: 4.8-11.8)
- Poor recent adherence (low FTC-TP) was a stronger marker of future discontinuation
than cumulative adherence (low TFV-DP)
 Self-reported adherence was not reliable in this group
 Poor short-term adherence is a marker of PrEP ambivalence and discontinuation risk
Spinelli JAIDS 2019

4. Zuckerberg San Francisco General
San Francisco General Hospital
High HIV Incidence after Stopping PrEP
 Many anecdotal reports:
- 18 HIV infections in people who stopped PrEP at City Clinic (SF
STD Clinic)
- HIV incidence of 3.9/100P-Y in people who stopped PrEP in
Montreal
 HIV incidence substantially higher after stopping PrEP:
Greenwald BMJ Open 2019; Shover AIBE 2019; Spinelli JIAS 2020

5. Zuckerberg San Francisco General
San Francisco General Hospital
Therapeutic Drug Monitoring Critical to
Understanding PrEP Adherence
Adherence
Measure
VOICE FEM-PrEP
Self-report 91% 95%
Returned pill counts 92% 88%
Plasma TFV
detection
29% 24%
Grant et al. NEJM 2010; Marrazzo et al. NEJM 2015; Van Damme et al. NEJM 2012; Baeten et al. NEJM 2012; Donnell et
al. JAIDS 2014

6. Zuckerberg San Francisco General
San Francisco General Hospital
Therapeutic Drug Monitoring Techniques not
Scalable—Need a Point-of-Care Test
 PrEP trials and demonstration projects have often relied
on pharmacologic metrics of adherence for
interpretation
 Usual methods to measure PrEP drugs in any matrix
(dried blood spot, urine, hair etc.) require liquid
chromatography tandem mass spectrometry (LC-MS/MS)
- Expensive
- Trained personnel
- Sample processing/shipping time
1Hendrix ARHR 2016; 2Hendrix PLOS One 2013; 3Calcagno. Pharmacogenomics 2016; 4Anderson Sci Trans Med 2012; 5Castillo-Mancilla. ARHR 2013; 6Castillo-Mancilla.
ARHR 2015; 7Zheng. J Pharm Biomed Anal 2014; 8Liu PLOS One 2014; Rosen. Anal Chem 2016;10Koenig HIV Med 2017; 11Simile. J Pharm Biomed Anal. 2015; 12Haaland
AIDS 2017; 13Lalley-Chareczko. Antiviral Ther 2017
• Antibody-based tests allow for rapid point-of-care testing

7. Zuckerberg San Francisco GeneralSan Francisco General Hospital
Developed one of first antibodies highly selective for
tenofovir, then developed a point-of-care test
• Evaluated for antibodies that bind to enzyme-
labeled tenofovir derivatives; found one with
high selectivity1
• Tenofovir levels measured by ELISA with this
antibody  high correlation and agreement with
LC-MS/MS levels2
• Developed a lateral flow assay (LFA):3 a point-of-
care platform to measure TFV (yes/no) in urine
• Adherence measured over 4-7 days
1Gandhi. EClinicalMedicine 2018; 2Gandhi JAIDS 2019; 3Gandhi AIDS 2020

8. Zuckerberg San Francisco GeneralSan Francisco General Hospital
High accuracy of the
POC Test Readouts
Negative Positive
Urine Tenofovir Point of Care TestELISAUrineTenofovirLevel
104
106
105
1500
ng/ml
 684 samples from 324
participants comparing LFA to
ELISA (comparator)
 Sensitivity: 505/505= 100%
(97.5% CI: 99.3)
 Specificity: 176/179= 98.3%
(95% CI: 95.2%-99.7%)
 Accuracy: 681/684= 99.6%
(95% CI: 98.7%-99.9%)
Partners PrEPSpinelli JAIDS 2020

9. Zuckerberg San Francisco General
How can we use the
LFA to motivate adherence?
 LFA highly accurate, ready for field testing
 PrEP: Increasing interest in drug-level feedback, targeting of
adherence interventions to those who can benefit most
- Express and virtual models decreasing contact, can POC test be
particularly helpful with alternate service delivery?
 Treatment: Sorting out resistance vs. non-adherence, prioritizing
HIV genotyping
1. Landovitz JAIDS 2017 2. Celum IAS Conference 2019 3. Koester AIDS Care 2015San Francisco General Hospital

10. Zuckerberg San Francisco General
San Francisco General Hospital
Drug-Levels Feedback Tested For First Time
in Sub-Analysis of iPrEx
 Can drug-levels be used to motivate improved adherence?
- “It’s just that it solidifies that all your efforts are…not just in vain.”
- Drug-level information alone for some however was a “non-event”
- Delays in feedback will decrease relevance (Koester AIDS Care 2015)
 Key Lessons:
1. Adherence information alone is not relevant unless it is motivational and leads to next
steps
2. Adherence counseling and feedback should be real-time if possible

11. Zuckerberg San Francisco General
San Francisco General Hospital
From Drug-Level Feedback to
Targeted Adherence Counseling
 Targeted motivational interviewing-based
adherence counseling using drug-levels
- Highly acceptable (>90%) and effective (fig.)
 However, trained research staff, long visits
 Delays limit impact (3 weeks)
Landovitz (JAIDS 2017)
 HPTN 082 in tested in young women
- Enhanced adherence counseling layered on
adherence clubs, SMS support
- Drug-level feedback no impact; very low
adherence (25-64% detected)
- Operational challenges with 2-month delay
Celum (IAS Conf. 2019)
Detectable
PlasmaTFV
Undetectable
PlasmaTFV

12. Zuckerberg San Francisco General
San Francisco General Hospital
Key Lessons:
 Drug-Level Feedback  Targeted Adherence
Counseling
 As real-time as possible
 Likely need to layer with other efficacious
interventions (SMS support, alternate service
delivery, etc.)

13. Zuckerberg San Francisco GeneralSan Francisco General Hospital
Discussion: Useful in PrEP but Real-Time
Adherence Information could also Inform ART
ART Adherence Measure
High Low
HIVViral
Load
Suppression
Viremia
Adherence information enhances interpretation of viral load
Yager JL, et al. J Int Assoc Provid AIDS Care. 2019;Jan-Dec. Slide credit to Jose Castillo-Mancilla

14. Zuckerberg San Francisco General
Limitations of the Assay
- Recent adherence information is susceptible to “white-coat effects”
(rare for PrEP1,2)
- Will need to test interventions using urine test with cumulative
adherence metric as outcome (TFV levels in dried blood spot or hair) in
PrEP
1. Blair CROI 2020 2. Koss CID 2018San Francisco General Hospital

15. Zuckerberg San Francisco General
Future Directions
- Testing drug-level targeted counseling in young Kenyan Women using
the POC test (PUMA study NCT03935464)
- U.S. Young MSM receiving brief motivational interviewing targeted by
the POC test (PrEP2-BAY study K23MH122286)
- Investigating use of the assay on plasma samples
- Developing cut-off of the test for TAF using urine samples collected
from the TAF-DBS study (PI: Pete Anderson)

16. Zuckerberg San Francisco General
Acknowledgements
 Mentors
- Monica Gandhi MD, MPH
- Susan Buchbinder MD
- Diane Havlir MD
 Abbott Rapid Diagnostics
- Carsten Buenning PhD
- Luis Gonzalez PhD
- Julian Braz PhD
San Francisco General Hospital