Jill Blumenthal, MD Assistant Professor of Medicine Division of Infectious Diseases and Global Public Health Department of Medicine University of California, San Diego

1. HIV & Global Health Rounds
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physicians, and researchers. The goal of these presentations is to
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HBV, HCV, TB, and other infectious diseases of global significance.
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presenter’s express permission.

2. Prevention in Her Hands:
Findings from a PrEP
Demonstration Study of
Cisgender Women
in Southern California
Jill Blumenthal MD MAS
Assistant Professor, Department of ID/GPH
2/28/20

3. Disclosures
• Drug was donated by Gilead Sciences

4. HIV Epidemiology of Women in the United
States and California
• Women made up 19% of the 38,789 new HIV diagnoses in the US in 2017.
• 23% of the ~1.1 million living with HIV
• Blacks and Latinas disproportionately affected by HIV
• US: 7,401 diagnosed with HIV in 2017, 59% were Black, 16% Latina, 20% White
• California: 499 diagnosed with HIV in 2017 (4,495 total), 25% Black, 38% Latina, 25%
White
CDC, HIV surveillance Report 2017; AIDSVu, HIV in California 2018

5. PrEP Use in Women in the United States
• Emtricitabine/tenofovir
disoproxil fumarate (F/TDF)
approved for PrEP use in
cisgender women
• 468,000 women living in the US
may meet eligibility criteria to
take PrEP
• Rates of PrEP uptake are
particularly low among women
• Even lower among Black
and Latina women
• In CA 15,218 PrEP users in 2018
• 4.7% in females
Smith DK, Jour Miss State Med Assoc Dec 2015; Bush S, ASM Microbe 2016; AIDSvu

6. Data on PrEP in US
Women
• Most of the work on PrEP in women
comes from international studies
• Paucity of data on women in the US
comes from focus groups and one
published clinical trial from 2017
Flash CA, AIDS Pt Care STDs, 2014; Auerbach JD, AIDS Pt Care STDs, 2015; Seidman D, R4P 2016; Gulick RM, Ann Int Med 2017. Amico R, JIAS 2019.

7. CI: 96 - 99
F/TDF (7x/week)
99%
F/TDF (~1x/24h)
94%
CI: -17 - 100
Adherence is Important…
Anderson P et al, Sci Transl Med, 2012
Grant RM et al, Lancet 2014
Donnell D et al, JAIDS, 2014
Cottrell ML et al, JID, 2016
Some adherence forgiveness with
retained protection
6-7 doses per week
likely required
Slide courtesy of Landovitz
CROI 2015

8. …but Controversial!
• The relative importance of mucosal tissue versus systemic drug
concentrations to PrEP efficacy is unknown
• CDC PrEP guidelines for F/TDF acknowledge lack of scientific consensus on
protective drug exposure in specific body tissues
• Time to achieve maximum intracellular concentrations of TFV-DP in:
• PBMCs (20 days)
• rectal tissue (7 days)
• cervicovaginal tissue (20 days)
• Other studies suggest that men and women taking F/TDF will reach
protective levels after 7 days of dosing
Anderson, PL et al AAC 2018; CDC PrEP Guidelines 2017

9. Week 48 Plot
CCTG 595: Text Message Response Predicts Tenofovir Levels in MSM Taking PrEP
Blumenthal, et al. Presentation at IAPAC 2017.

10. iNSC is a way to have a
discussion about sexual
health, adherence and
overall wellbeing by
creating a safe, genuine
space
iNSC is NOT about getting
pills to mouths. It is about
facilitating CONTEXTS and
MOTIVATION to help
moving to someone’s next
step towards safety
Integrated Next Step Counseling
Amico KR, et al. AIDS and Behav 2012; Grant RM, et al. Lancet ID, 2014; Bekker LG, et al, Lancet ID, 2018; Hosek SG, et al, JAIDS 2017.

11. PrEP Adherence Enhancement Guided
by iTAB and Drug Levels for Women (AEGiS)
A Pilot Demonstration Project to Operationalize PrEP as part of
Combination Prevention with Intensified Adherence Support Among
Women in Los Angeles and San Diego Counties

12. Methods (1)
• 48-week clinical trial to estimate PrEP adherence, retention and persistence
of n=136 HIV-negative women ≥18 years old at risk for HIV taking once daily
F/TDF
• Enrollment: 6/2016–10/2018
• 4 LA sites: AIDS Project LA, To Help Everyone Health and Wellness Center,
Harbor UCLA & USC
• 1 SD site: Antiviral Research Center at UCSD
• Study visits: Screening, weeks 0, 4, 12, 24, 36 and 48 with phone call at wk 60
• CASI to assess baseline demographics and HIV risk factors; regular
surveillance of HIV risk and medication behavior
• Routine lab testing for safety, pregnancy, HIV and STIs

13. Methods (2): Multimodal Adherence Interventions
• Technology: iTAB (individualized Texting for Adherence Building) 2-
way Text Messaging
• Biomarker: Intra-erythrocytic TFV-DP level in dried blood spots
• Titrated Counseling: Integrated Next Step Counseling (iNSC), targeted
iNSC, PrEP-STEPS

15. Methods (3): Eligibility
Inclusion Criteria
• Assigned female at birth and identifies as female gender
• 18 years or older
• English or Spanish Speaking
• HIV-negative; Creatinine clearance > 60 ml/min
• At recurrent and substantial risk for acquiring HIV infection (at least one):
1. Condomless sex in the last 3 months with one or more male partners of unknown HIV status known to
be at substantial risk of HIV infection (IDU, bisexual, sex for goods, recently incarcerated, from a
country with HIV prevalence >1%, interpersonal partner violence);
2. STI (rectal or vaginal gonorrhea or syphilis) diagnosis during the last 6 months
3. Previous post-exposure prophylaxis (PEP) use during the last 12 months
4. Has at least one HIV-infected sexual partner for > 4 weeks
5. Sex for exchange of money, goods or services
Exclusion Criteria
• Signs of symptoms for primary HIV infection

16. Methods (4) : Adherence Outcomes
• Objective measures
1. TFV-DP concentrations in dried blood spots
• Concentrations ≥1050 fmol/punch= ≥ ~6 doses per week
• Concentrations ≥ 700 fmol/punch = ≥ ~4 doses per week
2. TFV-DP concentrations in hair
• Subjective measures
1. iTAB: proportion of participants responding positively to daily
iTAB text prompts over 30 days prior to study visits
2. Various self-report questions

17. Methods (5): Statistics
• Descriptive summaries
• Wilcoxon rank sum to compare protective TFV-DP
concentrations and proportion of positive iTAB responses
• Disease incidence rate

18. Results (1): Study Flow and Demographics

19. BASELINE SOCIODEMOGRAPHICS
AND RISK FACTORS (n=136)
N (%)
Age Mean (SD) 40 (11)
Race/Ethnicity
Non-Hispanic White
Non-Hispanic Black
Latina
Other
30 (22%)
52 (38%)
26 (19%)
28 (21%)
Education - ≤ High School 51 (45%)
Income - < $2000 per month 74 (68%)
Employment - Unemployed/Unable to work 60 (47%)
Number sex partners last 3mo Median (IQR) 1 (1-3)
STI diagnosed at baseline - positive 12 (9%)
AUDIT - high risk 5 (4%)
DAST - severe/substantial risk 13 (10%)
IPV last year - yes to any 56 (41%)
Pregnancy Interest - yes 31 (23%)

20. Results (2): Overall Adherence

21. Results (3): DBS Adherence by Week
Wk 4, n=117
n (%)
Wk 12, n=102
n (%)
Wk 24, n=80
n (%)
Wk 36, n=69
n (%)
Wk 48, n=66
n (%)
≧1050 (6+ dose/week) 54 (46%) 45 (44%) 29 (36%) 28 (41%) 25 (38%)
≧700 (4+ dose/week) 84 (72%) 62 (61%) 54 (68%) 45 (65%) 42 (63%)
Of 120 participants with drug concentrations measured:
• n=67 (56%) had at least one 6+ dose/week; 22 (18%) had consistent 6+ dose/week
• n=90 (75%) had at least one 4+ dose/week; 53 (44%) had consistent 4+ dose/week

22. Results (4): iTAB Adherence
Study Visit N TVF-DP concentration
(fmol/punch)
Proportion positive iTAB
Responses, mean (SD)
P-value
Week 4 58
50
<1050
≧1050
0.49 (0.40)
0.80 (0.32)
<0.001
Week 12 55
44
<1050
≧1050
0.53 (0.38)
0.76 (0.31)
0.005
Week 24 49
28
<1050
≧1050
0.61 (0.34)
0.77 (0.27)
0.029
Week 36 39
27
<1050
≧1050
0.49 (0.40)
0.78 (0.25)
0.008
Week 48 38
24
<1050
≧1050
0.47 (0.39)
0.71 (0.32)
0.03

23. Results (5): Retention and Persistence
Week 4 Week 12 Week 24 Week 36 Week 48 Week 60
Completed visit (of
n=136); n (%)
121 (89%) 110 (81%) 98 (72%) 83 (61%) 83 (61%) 65 (48%)
On PrEP (of completed
visit); n (%)
103 (85%) 91 (83%) 72 (73%) 50 (72%) 62 (75%) 36 (55%)
Reasons for early discontinuation Total n=52 n (%)
Missed end of study visit 37 (71%)
Request by participant to withdraw
No longer feels at risk or wants to take
Unable to attend visits/moved
Side Effects*
PCP instructed to stop
PrEP outside study
Unknown
15 (29%)
5
6
1
1
1
1
*Not thought to be study-related

24. Results (6): Reasons for non-Persistence
Reasons not on PrEP Week 4-48 (n=31) Week 60 (n=26)
Worry about side effects / long-term effects 14 6
Don’t want to take pills - 3
Don’t feel like it works 2 -
Can’t stick with taking it 3 -
Not having sex / not at risk 1 4
Monogamous 2 1
Medical issues 3 1
Have not seen doctor - 2
Lack of insurance - 4
Became pregnant 1 1
Stolen / Worry might get stolen 2 1
Other 3 3

25. Results (7): Adverse Events
Total Decrease in CrCl* Study-related (or
possibly)**
Number of Grade 2-4 AE events
Grade 2
Grade 3
Grade 4
164
150
14
0
127
118
9
-
10
8
0
-
Number of participants who
experienced at least 1 AE
72 - -
*Grade 2 AEs for creatinine clearance (CrCl) are determined by result of <90 to 60ml/min or 10 to <30% decrease from
screening/baseline. Grade 3 AEs for CrCl are determined by result of <60 to 30 ml/min or 30 to <50% decrease from
screening/baseline.
**2 unknown if study-related

26. Results (8): HIV and STI Incidence
• STI incidence rate: 5 cases/100 person-years
• n=6 incident syphilis (1), gonorrhea (2), chlamydia infections (3)
• HIV incidence rate: 0 cases/100 person-year

27. Results (9): Pregnancy
• 7 pregnancies and 1 false-positive
• 5 to term, 1 miscarriage, 1 abortion

28. Discussion (1)
• Adherence
• Good levels when using systemic drug coverage targets
• Consistent over time
• iTAB may be good surrogate for objective adherence
• Retention
• Worse over time-- similar to previous PrEP studies
• Little information about non-retention
• Persistence
• Most who return are taking PrEP but if they aren’t returning…
Rusie et al, CID 2018; Chan et al. JIAS 2016

29. Discussion (2)
• Adverse events
• Despite concern for more AEs in cisgender women, only 1
person left study related to AEs
• However, most commonly cited reason for non-persistence
• Many CrCl declines but not clinically relevant
• HIV/STI incidence
• Similar to previous PrEP study in US
• Poor data on STI incidence in cisgender women in PrEP
studies
Kojima, et al. AIDS 2019.

30. Conclusions
• Cisgender women in a PrEP demonstration project had mixed adherence
and retention
• Many had protective TFV-DP concentrations
• Glass half-empty when considering the protective vaginal concentrations
• Over 25%lost to follow up and less than half were taking PrEP at week 48
• Few adverse events; Low HIV and STI incidence rates
• US PrEP programs may need to consider offering prevention alternatives
for women who discontinue or struggle with adherence
• Integrating PrEP delivery within other valued medical or social services
may promote and augment HIV prevention efforts

31. Future Directions
• Effect of inflammation on CVF tenofovir levels (CFAR Developmental -
Gianella/Morris)
• Qualitative data on barriers and facilitators to PrEP adherence in
serodiscordant couples (NIH KL2)
• Qualitative data on motivations and barriers/facilitators to PrEP
adherence in discordant reporters (NIH KL2)
• Predictors of adherence and retention

32. Acknowledgements
Our amazing
study participants!
LAC-PATH
Raphy Landovitz
Ryan Kofron
Rivet Amico
Christina Psaros
Gifty Ntim
U of Colorado
Pete Anderson
Lane Bushman
CCTG
Sheldon Morris
David Moore
Jamila Stockman
Sonia Jain
Feng He
Eric Ellorin
Leah Burke, Lizzy Lampley
Yvette Longduriyang
Jordan Silva, Kelly Walsh
Deedee Pacheco
Katya Corado
Janie Caplan
Kathleen Jacobson
Gilead Sciences
Richard Haubrich
Jim Rooney
Funding
CHRP-PR15-SD-005B
1KL2TR0001444 (to JB)

34. cfar.ucsd.edu

35. Developmental
• Supports new investigators and new ideas
in HIV research with grants and mentorship
• Awarded more than $5.1 million in funding
• Awards from $30,000 - $50,000 for one year
• Grant recipients have earned more than
$181 million in subsequent funding
Contact us! Website: cfar.ucsd.edu Email: cfar@ucsd.edu
Developmental Core
Director
Joshua
Fierer, MD
Associate Director
Mary
Lewinski, MD, PhD
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rights reserved.

36. International
• Empowers emerging foreign investigators to
respond to and manage their HIV epidemics
in low- and middle-income countries (LMIC)
• Provides pilot funding to new partners to
jump-start research in targeted settings
• Awards up to $40,000 for one year, with at
least half designated for international use
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Co-Directors
Robert
Schooley, MD
Steffanie
Strathdee, PhD
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International Core

37. SD CFAR Upcoming
Funding Opportunities
© Copyright 2020 Regents of the University of California. All rights reserved.
Developmental Grant Deadlines: https://bit.ly/2SdFOfg
• May 18, 2020—one-time change due to Review Committee schedule
• December 1, 2020
International Pilot Grant Deadlines: https://bit.ly/36TkzEI
• April 1, 2020
• No October cycle in 2020 due to National CFAR Meeting in San Diego
More information: https://bit.ly/2uffxoR
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More information and resources at
https://bit.ly/2vMOd1
O-K Reviews
Mock study sections for
NIH F, K and R proposals
May 7, 2020 NIH due date
• Abstracts due March 12, 2020
• Draft applications due March 26, 2020
• In-person review panel April 9, 1:00 – 4:00 pm
September 7, 2020 NIH due date
• Abstracts due July 13, 2020
• Draft applications due July 27, 2020
• In-person review panel August 7, 1:00 – 4:00 pm
January 7, 2021 NIH due date
• Abstracts due November 16, 2020
• Draft applications due November 30, 2020
• In-person review panel December 14, 1:00 – 4:00 pm
SD CFAR Upcoming
Funding Opportunities
Contact us! Website: cfar.ucsd.edu Email: cfar@ucsd.edu

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Email: cfar@ucsd.edu
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