Transcript Preparing for PrEP - Community Clinic Association of Los Angeles

PREPARING FOR
PREP: UNDERSTANDING
ACCESS AND CLINICAL
PRACTICE
Janie Caplan, MD, Infectious Diseases Fellow, UCLA
Gifty-Maria Ntim, MD, MPH Medical Director, APLA Health & Wellness
David Evans, Director of Research Advocacy, Project Inform
Describe PrEP Usage and Approved Medications
Currently Provided at Community Health Centers and
their Effectiveness
Gifty-Maria Ntim, MD, MPH
Medical Director, APLA Health & Wellness
Disclosures
I have nothing to disclose personally however APLA Health
& Wellness has received funding in the past from Gilead
HIV in Los Angeles County
HIV Prevention
Comprehensive Approach
• Behavioral Interventions
• Biomedical Interventions
• TasP
• PrEP
• PEP
• Structural Interventions
Pre-Exposure Prophylaxis with Truvada
• The only medication regimen approved by the Food and
Drug Administration and recommended for PrEP with all
the populations specified in this guideline is daily TDF
(Tenofovir) 300 mg co-formulated with FTC (Emtricitabine)
200 mg (Truvada) (IA)
• TDF alone has shown substantial efficacy and safety in trials with
IV drug users and heterosexually active adults and can be
considered as an alternative regimen for these populations, but not
for MSM, among whom its efficacy has not been studied. (IC)
• The use of other antiretroviral medications for PrEP, either in place
of or in addition to TDF/FTC (or TDF) is not recommended. (IIIA)
• The prescription of oral PrEP for coitally-timed or other noncontinuous daily use is not recommended. (IIIA)
http://www.cdc.gov/hiv/pdf/prepguidelines2014.pdf
Let’s Talk About Sex
Who May Benefit from PrEP
http://www.cdc.gov/hiv/pdf/prepguidelines2014.pdf
California PrEP Coverage at a Glance
• Medi-Cal covers PrEP 100% if a single household income is less than
$16,243 a year
• Covered California offers reasonable access if you choose an
appropriate plan (Bronze, Silver, Enhanced Silver 73,87,94, Gold,
Platinum)
• Gilead offers co-pay assistance to help cover up to $3,600 /year
Assistance can be used to cover pharmacy deductibles and co-pays for
medication itself (no income requirements)
• Gilead offers free medication to those who do not have insurance (i.e.
undocumented individuals, those who are not eligible to sign-up through
market place , Medi-Cal pending, waiting for open enrollment, etc)
Sequence of Appearance of Laboratory
Markers for HIV-1 Infection
http://www.cdc.gov/hiv/pdf/hivtestingalgorithmrecommendation-final.pdf
Prescribing Truvada for PrEP
Adherence and Counseling
Establish trust and bidirectional communication with your patient
• Provide simple explanations and education
• Discuss medication dosage and schedule
• Discuss management of common side effects
• Discuss the relationship of adherence to the efficacy of PrEP
• Discuss signs and symptoms of acute HIV infection and recommended actions
Support adherence
• Tailor daily dose to patient’s daily routine
• Identify reminders and devices to minimize forgetting doses
• Identify and address barriers to adherence
Monitor medication adherence in a non-judgmental manner
• Normalize occasional missed doses, while ensuring patient understands
importance of daily dosing for optimal protection e.g. ‘how many doses did you
miss in the last 7 days?’
• Reinforce success
• Identify factors interfering with adherence and plan with patient to address them
• Assess side effects and plan how to manage them
http://www.cdc.gov/hiv/pdf/prepguidelines2014.pdf
Concerns Raised by PrEP
• Side-effects and toxicity
• Drug resistance
• Adherence
• Risk compensation
• Access
• Cost
• Truvada’s ‘street value’
Common Asked Questions
1.
2.
3.
4.
5.
6.
7.
8.
How soon after starting PrEP can I have some
protection?
What side effects should I watch for?
What happens when I miss a dose of Truvada?
Why do I need to come in for refills?
Do I still need to use condoms?
What about the guy who was taking PrEP who recently
tested positive for HIV?
Is my body going to look weird after I start taking
Truvada?
Will Truvada affect my sex drive?
Sexually Transmitted Infections and PrEP
• Test for STIs every 3m and as needed based on exposure
vs. testing every 6m per CDC guidelines
Helpful ICD 10 Codes
• Z72.51
High Risk Heterosexual Behavior
• Z72.52
High Risk Homosexual Behavior
• Z72.53
High Risk Bisexual Behavior
Margaret “Janie” Caplan, MD
Fellow physician
Division of Infectious Diseases
David Geffen School of Medicine at UCLA
EVIDENCE FOR USE OF PRE-EXPOSURE
PROPHYLAXIS IN AT RISK POPULATIONS
Disclosures
 I have nothing to disclose!
Clinical Trials of Oral PrEP
iPrEx
Population
Location
Sample size
Intervention
Efficacy of
TDF/FTC
(ITT
analysis)
MSM and
Transgender women
US, Brazil, Ecuador,
Peru, South Africa,
Thailand
2,499
TDF 2
Partners
PrEP
Heterosexual men
and women
Heterosexual
HIV
serodiscordant
couples
Botswana
Kenya and
Uganda
1,219
4,758
Daily oral TDF or
Daily oral TDF/FTC* Daily oral TDF/FTC*
TDF/FTC*
75%
44%
62%
36 vs. 64
(95% CI, 15-63%)
9 vs. 24
(95% CI, 22-83%)
17 vs. 13 vs. 52
(95% CI, 5587%)
Grant et al N Engl J Med 2010
Thigpen et al N Engl J Med 2012
Baeten et al N Engl J Med 2012
*All as part of a comprehensive
prevention package*
 HIV testing
 Risk-reduction counseling and condoms
 Diagnosis and treatment of symptomatic STIs
(gonorrhea, chlamydia, syphilis, and HSV-2), as
well as screening in asymptomatic individuals and
partners
 +/- Referral for PEP if reporting a recent exposure
to HIV
 +/- Hepatitis B vaccination
Participants in PrEP Clinical Trials
Purple overall
Red 18-24 yo
Green < 18yo Blue US participants
Pace et al. CID 2013; 56 (8)
Clinical Trials in Women* Only
FemPrEP
VOICE
Kenya, South Africa, and
Tanzania
Uganda, South Africa,
Zimbabwe
Sample size
2,120
5,029
Intervention
Daily oral tablet
(TDF/FTC)*
Daily oral tablet
(TDF or TDF/FTC) or
vaginal gel (TDF)*
6%
-4.4%
33 vs. 35
(95% CI, -52-41%)
61 vs. 60
(95% CI, -149-27%)
Location
Efficacy of TDF/FTC
(ITT analysis)
*cis-gender
Van Damme et al. N Engl J Med 2012
Marrazzo et al. N Engl J Med 2015
Women in Clinical Trials
iPrEx
TDF 2
Partners
PrEP
Population
MSM and
Transgender women
Heterosexual men
and women
Heterosexual HIV
serodiscordant
couples
Location
US, Brazil, Ecuador,
Peru, South Africa,
Thailand
Botswana
Kenya and
Uganda
Sample size
2,499
1,219
Intervention
Daily oral TDF/FTC*
Men:
Daily
oral 80%
TDF/FTC*
4,758
Daily oral TDF or
TDF/FTC*
Efficacy of
TDF/FTC
(ITT analysis)
44%
62%
75%
(25-97)
36 vs. 64
vs. 24(-22-81) 17 vs. 13 vs. 52
Women:949%
(95% CI, 15-63%)
(95% CI, 22-83%)
(95% CI, 55-87%)
Grant et al N Engl J Med 2010
Thigpen et al N Engl J Med 2012
Baeten et al N Engl J Med 2012
Women in Clinical Trials
Population
iPrEx
TDF 2
Partners
PrEP
MSM and
Transgender women
Heterosexual men
and women
Heterosexual HIV
serodiscordant
couples
Botswana
Kenya and
Uganda
Sample size
US, Brazil, Ecuador,
Peru, South Africa,
Thailand
2,499
Intervention
Daily oral TDF/FTC*
Location
Efficacy of
TDF/FTC
(ITT analysis)
1,219
Daily oral TDF/FTC*
4,758
Daily
TDF or
Men:oral
84%
TDF/FTC*
(54-94)
44%
62%
75%
36 vs. 64
(95% CI, 15-63%)
9 vs. 24
(95% CI, 22-83%)
17 vs. 13 66%
vs. 52
Women:
(95% CI, 55-87%)
(28-84)
Grant et al N Engl J Med 2010
Thigpen et al N Engl J Med 2012
Baeten et al N Engl J Med 2012
What happened?
ADHERENCE
Clinical
Efficacy
Pharmacology
Relationship Between Effectiveness
and Adherence in Microbicide & PrEP
Trials
100
Pearson correlation = 0.86, p=0.003
Pearson correlation = 0.86, p=0.003
Effectiveness (%)
80
CAPRISA 004
iPrEX
60
TDF2
Partners PrEP (TDF)
PartnersPrep
(TDF)
40
Partners PrEP (Truvada)
PartnersPreP
(FTC)
20
FemPrEP
0
0
-20
10
20
30
40
50
60
70
80
90
VOICE (TDF)
VOICE (Truvada)
VOICE (TFV gel)
-40
-60
Percentage of Participants’ Samples with detectable drug levels
(Analysis based on a subset of total trail participants, Pearson correlation = 0.86, p=0.003)
R Landovitz, SS Abdool Karim, personal communication
TDF Concentrates 10-100x More in Rectal
Tissue than in Cervico-vaginal Tissues
Days post single-dose
Patterson KB et al. Sci Transl Med. 2011.
Maximizing the Potential
Effectiveness
TDF/FTC (~7x/week)
TDF/FTC (~1x/24°)
99%
9294%
~1 WEEK
to reach
protective
levels
CI: 96 - 99
Some adherence forgiveness with
retained protection
Anderson P et al, Sci Transl Med. 2012.
~3 WEEKS
to reach
protective
levels
CI: -17 - 100
6-7 doses per week likely
required
Donnell D et al, JAIDS. 2014.
Cottrell ML et al, R4P, 2014.
Dosing Strategies
 Intermittent dosing is NOT recommended
at this point.
 IPERGAY study: “On Demand” PrEP with
TDF/FTC, only in MSM1
 HPTN067 (ADAPT): non-daily PrEP in South
African women2
 Prelim data: Daily dosing fostered better adherence,
better coverage of potential sexual exposure, and
more sustained use
 Take Home Point: Daily dosing!
1.
2.
Molina JM, et al. CROI, 2015.
Bekker LG, et al. CROI, 2015.
Efficacy Depends on Adherence




Next Step Counseling1
CDC Guidance2
Text messaging3,4
“Smart” devices5,6
1. Amico KR et al. AIDS Behav. 2012.
2. CDC Clinical Practice Guidelines. 2014.
3. Finitsis DJ et al. PLoS ONE. 2014.
4. Moore D et al. CCTG 595.
5. Bekker LG et al. HPTN 067
6. Gulick RM et al. HPTN 069
Risk Compensation
 Theory that people adjust their behaviors in
response to perceived level of risk
 Historical example: Birth control and concern
that its increased availability would promote
risky sexual behavior
 Does PrEP use result in increase in risky
behavior (e.g. less condom use)?
 PrEP trials have not seen risk compensation.
 HOWEVER, in these trials, participants
knew they might be getting a placebo.
 What will happen in the real world setting?
 iPrEX Open Label Extension (OLE): no significant
change in sexual practices
Sexually Transmitted Infections
 High incidence of STIs during follow-up in
PrEP studies: increase in unprotected sex or
increase in detection/screening?
 Screening for STIs during PrEP use
 CDC recommendation: Based on symptoms,
and/or every 6 months for bacterial STIs
 Evidence from PrEP implementation studies in
New York and San Francisco suggesting more
frequent, routine screening q3months might detect
more incident STIs
HIV Resistance
 Resistance is rare in clinical trials of PrEP
 Resistance when PrEP is started accidentally
during undiagnosed primary HIV infection – 8/29
(27.5%)
Number of HIV Seroconverters on Active PrEP Arms With HIV Resistance
N
mITT (oral drug)
HIV Infected After Enrollment,
Resistant / Seroconverters
(randomized to active drug)
iPrEx[1,2]
1224
0/36
Partners PrEP[3,4]
3140
4/51
TDF2[5]
601
0/10
FEM-PrEP[6,7]
1024
4/33
VOICE[8]
1978
1/113
TOTAL
7967
9/243 (3.7%)
Modified Total§
7967
5/243 (2.0%) or 0.06% of exposed
Trial
1.
2.
3.
4.
Liegler T, et al. J Inf Dis. 2014.
Grant RM, et al. N Engl J Med. 2010.
Baeten JM, et al. N Engl J Med. 2012.
Lehman DA, et al. J Inf Dis. 2015.
§After exclusion of resistance likely to be transmitted
5.
6.
7.
8.
Thigpen MC, et al. N Engl J Med. 2012.
Van Damme L, et al. N Engl J Med. 2012.
Grant RM, et al. AIDS. 2015.
Marrazzo JM, et al. NEJM. 2015
Ongoing Research
 Other oral antiretrovirals as PrEP
 Maraviroc (HPTN069)
 Long Acting Therapies
 Vaginal rings – dapivirine
 Injectables – rilpivirine; cabotegravir
 Immunotherapies – VRC01
 Intermittent (i)PrEP
 Demonstration projects
 Cis-gender and transgender women
22 February 2016
ASPIRE
Population
The Ring Study
Heterosexual, cis-gender, HIV-negative,
18-45 year-old women
Funding
NIH/MTN
IPM
Location
15 sites in South
Africa, Zimbabwe,
Uganda, Malawi
7 sites in South
Africa and Uganda
2,629 (1:1)
1,959 (2:1)
Sample Size (randomized)
Intervention
monthly dapivirine vaginal ring
Follow-up
#HIV infections (d vs placebo)
One year
Two year
71 vs 97
77 (5.9%) vs 56
(8.6%)
Efficacy (reduced risk of HIV infection)
Overall
27% (1, 26)
31% (0.9, 51)
Age < 21y
-27% (-133,31)
15%
Age >21y
56% (31,71)
37% (3.5,59)
Ongoing Research
 Local demonstration projects funded by
California HIV/AIDS Research Program
(CHRP)
 Currently completing follow-up of MSM
projects
 Project in cis-gender women nearing
start of enrollment
 Funding for projects focusing on
transgender persons
Ongoing Research
AEGiS – PrEP Adherence Enhancement
Guided by iTAB and Drug Levels for Women
 Los Angeles and San Diego
 Truvada® as part of a combination prevention
package with enhanced adherence support in
the forms of counseling, text messaging, and
drug levels for 135 heterosexual, cis-gender
women at risk of HIV infection
 5 sites (4 in LAC, 1 in SD)
 Estimated enrollment beginning
~late April 2016
PrEP Awareness, Access and Roll-Out
Considerations for Advocacy and Policy
David Evans, Director of Research Advocacy
Disclosures
• Project Inform receives restricted and unrestricted funding from
pharmaceutical companies, including Gilead.
• Today’s educational forum and presentation have been created
independently of pharmaceutical influence or review.
About Project Inform
• An HIV and Hepatitis C advocacy, education and policy organizations that
has been in existence since 1985.
• Work on biomedical prevention began in 2011, with calls for
demonstration projects to determine real world efficacy and more recently
work on implementation of PrEP programs in California and elsewhere.
• Project Inform is one of the oldest organizations working on pricing of and
access to HIV medications both for those living with HIV and now those at
risk of HIV as well.
Over-all topics for today:
• EFFECTIVENESS: What have we learned about the effectiveness of PrEP in
men who have sex with men (MSM) and cis-gender heterosexual women
and men?
• DOSING: How adherent does someone need to be? How long must you
take it for it to be effective and how long do you need to keep taking it
after risk stops?
• ACCEPTANCE AND AWARENESS: What do various communities think and
know about PrEP and how might that affect its use? What don’t we know?
• ROLL-OUT: How is PrEP being taken up? What are barriers to access? Are
they changing?
• NEW STRATEGIES: What might PrEP look like in 2020? New drugs, new
delivery methods.
PrEP Use: LA County
AWARENESS and ACCEPTANCE:
Presentation by Kevin Delaney of CDC at CROI 2016 on PrEP awareness,
acceptability and use among MSM in the United States.
• Two surveys: May to August 2012 (n=2,794) and October 2014 to May 2015
(n=8,406)
• Awareness increased from 45% to 68%
• Willingness to consider increased from 39% to 50%
• Use increased from 0.5% to 4.9%
AWARENESS and ACCEPTANCE:
• Hypothetical acceptability is a somewhat poor predictor of uptake of new
innovations, but can prompt the need for research.
• First PrEP study exclusively in black MSM reported at CROI 2016
(HPTN073).
• 226 men (40% under 25 yrs) offered PrEP.
• Most (79%) decided to take it. 68% remained on PrEP for at least 26
weeks.
• Periodic surveys among MSM in NYC have found an increase of PrEP use
over time, starting at 2% in 2013 to 14.8% in 2015. Race did not affect
likelihood of PrEP use, nor did age or income, but increased risk increased
it. Being uninsured reduced the likelihood of PrEP use.
AWARENESS and ACCEPTANCE:
• Three surveys or focus groups among cis-gender
women indicated moderate levels of acceptance of
PrEP, though more studies are needed.
• Data in trans women and MSM are greatly needed.
Neither mentioned in CDC guidance. Concerns
reported over interactions with gender conforming
hormones and PrEP and effect on genital tissues.
• Almost no work has been done around persons who
inject drugs.
PrEP Use: U.S. EMR Scan by Gilead
Presented by Robert Grant, Gladstone 2015
PrEP Use: Kaiser Permanente SF
Presented by Robert Grant, Gladstone 2015
ROLL-OUT:
• Some factors influencing access:
• Stigma from friends, the community and
providers
• Lack of health insurance
• Incomplete health insurance with high
deductibles and co-pays
• Lack of knowledgeable and willing providers
• Lack of access to regular STI and lab tests
• Low perception of HIV risk
ROLL-OUT:
• Signs of improvement:
• Increased co-pay assistance
• New PrEP clinics and PrEP services expanding
even within cities with low resources
• More money for PrEP from local, state and
federal government
• More culturally competent educational
resources
• Greater recognition of the need to expand
existing PrEP services.
• Successful state budget request for PrEP
navigation and other services
ROLL-OUT: Other challenges and questions
• Continued disagreement about who should deliver
PrEP services.
• ID and HIV specialists or PCP and NPs?
• Other task shifting?
• Pharmacists?
• Ensuring the absence of acute infections (access to
4th generation AB/AG test)
• Proper levels of adherence and prevention support
(Scale up, scale down, scrape by with limited
resources?)
• Co-location or collaborative agreement with support
services?
Policy opportunities and discussions:
• Follow NY PrEP-DAP model in California – free
testing and medical visits – Gilead, PAN and PAF pay
for drugs.
• Expanded support for rural and low-resource areas
that allows flexibility while maintaining high
standards.
• Clearinghouse for PrEP education, implementation
and medical practice best practices.
• Education that Ryan White infrastructure can be
used for non-funded services (e.g. RW admin can
support PrEP, which is not RW funded)
• Changing Ryan White to allow HIV prevention
Materials from Project Inform
• We have 5 printed materials on PrEP (order free copies):
• Is PrEP the right choice for you? (for both cisgender and
transgender MSM)
• PrEP: A new option for women for safer loving
How to get PrEP
• Transcending barriers for safer pleasure (for transgender
women)
• PrEP Flow Chart (an access guide to obtaining a prescription
and coverage for PrEP)
• Pocket point of access card
www.projectinform.org/prep
Resources
Clinical Recommendations, Guidelines and Tools
LA County
http://publichealth.lacounty.gov/dhsp/docs/PrEPServiceDeliveryChecklistProviders.pdf
http://publichealth.lacounty.gov/dhsp/docs/LACountyPEP-PrEP-ProviderDirectory515.pdf
CDC
http://www.cdc.gov/hiv/guidelines/preventing.html
Medication and Co-Pay Assistance
https://www.gileadadvancingaccess.com/copay-coupon-card
https://www.gileadadvancingaccess.com/get-started-advancing-access
https://www.copays.org/diseases/hiv-aids-and-prevention
Provider Directory for LA County
www.GetPrEPLA.com
http://getprepla.com/provider_directory.htmlPatient Support and
Resourceswww.PrepFacts.org
Contact Us
Janie Caplan, MD – David Geffen School of Medicine at UCLA
Email: [email protected]
Phone: 866-562-1048 (AEGiS)
Gifty-Maria Ntim, MD, MPH – APLA Health & Wellness
Email: [email protected]
Phone: 323.329.9929
David Evans, Project Inform
Email: [email protected]
Phone: 626-241-8267