Transcript Pre-Exposure Prophylaxis - Clinical Education Initiative

PRE-EXPOSURE PROPHYLAXIS
Jeffrey Kwong, DNP, MPH, ANP-BC
Assistant Professor
Director, HIV subspecialty
Director, Adult-Gerontology Primary Care
Columbia University
June 2015
DISCLOSURES
Gilead Sciences, Inc.
• Advisory Board
LEARNING OBJECTIVES:
By the end of this presentation, the learner will be able to:
1. Discuss the NYS and CDC Guidelines for Pre-Exposure
Prophylaxis (PrEP).
2. Describe selection of candidates for PrEP.
3. Discuss the management of the patient on PrEP.
4. Discuss PrEP therapy and side effects.
5. Discuss the challenges associated with PrEP.
6. Discuss follow-up care including labs, PrEP, and counseling.
Stage 3 (AIDS) Classifications and Deaths of Persons with HIV
Infection Ever Classified as Stage 3 (AIDS), among Adults and
Adolescents, 1985–2012—United States and 6 Dependent Areas
Note. All displayed data have been statistically adjusted to account for reporting delays, but not for incomplete reporting. Deaths
of persons with HIV infection, stage 3 (AIDS) may be due to any cause.
New HIV Infections
 World-wide 7,000 new infections per day
One new infection every 9 ½ minutes
WHO – HIV Data & statistics ( 2012)
Diagnoses of HIV Infection among Adults and
Adolescents, by Transmission Category,
2009–2013 — United States and 6 Dependent Areas
Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have
been statistically adjusted to account for reporting delays and missing transmission category, but not for incomplete
reporting.
a Heterosexual contact with a person known to have, or to be at high risk for, HIV infection.
b Includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or not identified.
“Treatment . . . costs are unsustainable.
Greater emphasis must be placed on
preventing new infections.”
– Institute of Medicine Report Brief,
November 2010
IOM. Preparing for the future of HIV/AIDS in Africa: a shared responsibility. November 29, 2010.
HIV Prevention: Toolbox for
Success
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•
•
Safer-sex counseling
Barrier protection
Syringe exchange
HIV testing
STI testing and treatment
PEP (postexposure prophylaxis)
PrEP (pre-exposure prophylaxis)
Treatment as Prevention (TasP)
HIV PrEP studies with favorable
outcomes
Study
Intervention Population
Effiicacy
(95% CI)
Caprisa O04
TDF
intravaginal gel
Heterosexual
women
39% (6-60%)
Partners
PrEP
TDF v
TDF/FTC v
Placeob
Heterosexual
couples
67% (44-81) <0.0001
TDF
75% (55-87) < 0.0001
TDF/FTC
TDF2
TDF/FTC v
placebo
Heterosexual
couples
63% (22-83), 0.01
iPrex
TDF/FTC v
placebo
MSM, TG women
44% (15-63) 0.005
Bangkok/CDC
TDF v
Placebo
IVDU
49% (10-72) 0.01
Baeten et al., 2013 JAIDS 63(2)
MMWR 2013, 62(23)
HIV PrEP Studies:
Favorable Outcomes
Study
Intervention
Population
Efficacy ( CI)
PROUD
TDF/FTC
Immediate vs
Delayed TDF/FTC
MSM, Transgender
women
86%
(CI 90%:58-96%),0.0002
Ipergay
TDF/FTC
Event driven dosing
MSM, Transgender
women
86%
(CI 95%: 40-99%),0.002
McCormack S et al. Pragmatic Open-Label Randomised Trial of Preexposure Prophylaxis: The PROUD Study. 2015 Conference on Retroviruses
and Opportunistic Infections (CROI), Seattle, USA,abstract 22LB, 2015.
Molina J-M et al. On Demand PrEP With Oral TDF-FTC in MSM: Results of the ANRS Ipergay Trial. 2015 Conference on Retroviruses and
Opportunistic Infections (CROI), Seattle, USA, abstract 23LB, 2015.
Disappointing Results of PrEP in
Women: FEM-PrEP and VOICE
 FEM-PrEP: Phase III study oral
TDF/FTC for high-risk women in Africa
April 18, 2011, study was ended early
because of lack of efficacy
– 35 vs 33 new HIV infections in the
placebo and FTC/TDF arms[1]
– TFV blood levels that use was too
low (< 40%) to assess efficacy
– 4 vs 1 patient with M184V/I in the
TDF/FTC and placebo arms
1.
2.
 VOICE: Phase IIB trial of women in
South Africa, Uganda, and
Zimbabwe[2]
– Daily oral TDF; daily oral
TDF/FTC; daily vaginal TFV 1%
gel
– DSMB stopped the daily oral
TDF arm in September 2011
and the daily vaginal gel arm in
November 2011, both for lack
of efficacy
– Daily oral TDF/FTC arm also
failed to show efficacy.
Van Damme L, et al CROI 2012. Abstract 32LB.
2. These data are available in press release format only, have not been peer reviewed, may be incomplete, and we await presentation or
publication in a peer-reviewed format before conclusions should be made from these data.
Wong et al., 2013 Abstract WEAC0104
PrEP Candidates
• PrEP is recommended as one prevention option for the following
adults at substantial risk of HIV acquisition
– Sexually active MSM
– Heterosexually active men and women
– Injection drug users
MSM
Potential
indicators of
substantial
risk of acquiring
HIV infection
 HIV-positive sexual
partner
 Recent bacterial STI
 High number of sex
partners
 History of inconsistent or
no condom use
 Commercial sex work
CDC, 2014
CDC. PrEP Guideline. 2014.
Heterosexual Women and Men
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HIV-positive sexual partner
Recent bacterial STI
High number of sex partners
History of inconsistent or no
condom use
 Commercial sex work
 In high-prevalence area or
network
Injection Drug Users
 HIV-positive injecting
partner
 Sharing injection
equipment
 Recent drug treatment
(but currently
injecting)
PrEP Key Points
• PrEP should not be offered as a sole intervention
• Lack of use of barrier protection is NOT a contraindication
for PrEP
• Clinicians should wait to prescribe PrEP until a
confirmation of a negative HIV test.
• Patients presenting or suspected of ACUTE HIV should be
screened with HIV RNA testing.
• Discontinue PrEP immediately for patients who receive a
positive HIV test result.
NYS PrEP Guidance, 2014
Key Points: PrEP Guidance
– TDF/FTC is the only FDA approved regimen
– Daily dosing of PrEP is the only proven effective
regimen
– PrEP efficacy was demonstrated with HIV testing
and other prevention & risk reduction services
Preexposure Prophylaxis for the Prevention of HIV Infection in the United States – 2014 Clinical Providers’ Supplement
Absolute Contraindications for PrEP
• HIV positive
• Creatinine Clearance < 60
NYS PrEP Guidance, 2014
Pre-Prescription Assessment
Checklist
 Screen for symptoms of acute HIV
infection in last 6 weeks
 Review medication list
 Are there any potential
interactions or synergistic
toxicities?
 Assess mental health and
substance use
 Explore patient knowledge of PrEP
and Motivation for initiating
medication
 Evaluate willingness to take DAILY
PrEP
 Is the patient connected to primary
care?
 Is patient involved with HIV positive
partners?
 Are they on ARV
 Is there resistance data
available?
 Screen for domestic violence
 Assess Housing Status
 Do they have the means to pay for
PrEP?
 Evaluate fertility goals and
contraception use in female PrEP
Candidates
NYS PrEP Guidance, 2014
Pre –Prescription Laboratory Evaluation
New York State PrEP Guidance 2014
PrEP Guidance: Beginning treatment
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Prescribe TDF-FTC daily
Maximum 90 day supply
Renew after confirmatory HIV testing
If active HBV, consider using TDF/FTC for
treatment of HBV and prevention of HIV
• Provide risk-reduction and PrEP
adherence counseling, condoms
Preexposure Prophylaxis for the Prevention of HIV Infection in the United States – 2014 Clinical Providers’ Supplement
Key Components of Medication
Adherence Counseling
• Address adverse events[1]
• Identify barriers to adherence[1]
• Respond to missed doses with normalization and
nonjudgement, and emphasize importance of
adherence[1]
• Patient self-reporting may not reflect actual
adherence[2,3]
1. CDC. PrEP Guideline. 2014. 2. Van Der Straten A, et al. CROI 2014. Abstract
44. 3. Baxi SM, et al. CROI 2014. Abstract 953.
Elements of HIV risk-reduction
counseling in clinical settings
• Create and maintain a trusting and confidential
environment for discussion of sexual and substance abuse
behaviors.
• Build an ongoing dialogue with the patient regarding their
risk behavior.
• Reinforce that PrEP is not always effective in preventing HIV
infection, particularly if used inconsistently. Consistent use
of PrEP together with other prevention methods confers
very high levels of protection.
Preexposure Prophylaxis for the Prevention of HIV Infection in the United States – 2014 Clinical Providers’ Supplement
Follow-up and Monitoring
Follow-up
At Least Every 3 Mos
All patients
 HIV test
 Medication adherence
counseling
 Behavioral risk
reduction support
 Adverse event
assessment
 STI symptom
assessment
Women
 Pregnancy test (where
appropriate)
HBsAg+
After 3 Mos and at
Least Every 6 Mos
Thereafter
At Least Every
6 Mos
At Least Every 12
Mos
 Assess renal function
 Test for bacterial
STIs
 Evaluate need to
continue PrEP
 HBV DNA by quantitative assay*
*Every 6-12 mos.
CDC. PrEP Guideline. 2014.
NYS PrEP Guidance, 2014
New York State Plan to End AIDS
1. Identifying persons with HIV who remain
undiagnosed and linking them to health care;
2. Linking and retaining persons diagnosed with HIV to
health care and getting them on anti-HIV therapy to
maximize HIV virus supression so they remain
healthy and prevent further transmission; and
3. Providing access to Pre-Exposure Prophylaxis (PrEP)
for high-risk persons to keep them HIV negative.
New HIV Diagnosis - NYS
PrEP Implementation: Prescriptions
Jan 2012 - Sep 2013
Mean age was 38.2
Males (39.5 )
Females (36.8)
12.3% under 25 years old
• % males under 25 = 8.0%
• % women under 25 = 16.8%
What Are the Barriers to PrEP
Uptake?
• Users
– Unaware of HIV risk, PrEP
availability, or how to
access it
– No or delayed access to
clinical preventive care
– Uninsured or unable to pay
• Providers
– Unaware of intervention
– Uncertain how to deliver
the intervention
– Wary of complexity and
time involved
– Adherence challenges
– Discomfort with assessing
candidacy
– Concern about disclosure
and stigma
– Uncertain how to bill for
intervention
Consumer Demand for PrEP
• Increasing
awareness of PrEP
may results in
greater demand
PrEP: Perceptions & Attitudes
• Survey of Seronegative Partners (n=86)
• 56% Male 74% Heterosexuals
• Majority (94%) willing to use PrEP
• 26% would be more likely to have unprotected sex with HIVpositive partners and 20% with a new partner while using
PrEP.
• In addition, 27% suggested that it would be difficult to take
daily dose of PrEP and also consistently use condoms.
Tripathi, et al. (2013). Southen Med J Oct;106(10):558-64
PrEP Uptake
• Survey of online gay social networking site (n=9,179 men)
• 85.7% white, 3.9% Black, 7.5% Latino
Conclusions:
• 58.7% reported unprotected anal sex
• 3.2%
reported
nPEP, 1.2%
reported
PrEP
use MSM,
In order
tousing
increase
nPEP
& PrEP
among
• Although
84%care
had PCP,
only 53.9%
felt comfortable
talkingto
about
primary
providers
should
be educated
MSM sex
•
provide culturally competent care, so patients
PrEP Users:
feel free to discuss HIV risks that could be
– More comfortable talking with provider about MSM sex.
decreased by nPEP or PrEP
– 16-fold greater odds of having used nPEP
Mayer, et al. (2014). Early Adopters: Correlates of chemoprophylaxis use in an online sample of US
Men who have sex with Men. CROI 2014 Abstrat 952
PrEP Uptake: The Demo Project
• 48 week demonstration project in SF and Miami (MSM & TF)
• 53% uptake (49% in SF and 64% in Miami)
– (386 enrolled out of 726 eligible participants)
• Correlates of uptake:
– Prior awareness of PrEP
• (AOR 2.3, 95% CI 1.5-3.5)
– Unprotected anal sex with > 5 partners
•
(AOR 1.8, 95% CI: 1.0-2.2)
– > 1 episode of anal sex with HIV-infected partner
•
(AOR 1.8, 95%CI 1.2-2.6)
– Higher risk perception
• (AOR 1.9, 95% CI 1.2-2.8)
Cohen et al. (2014). Implementation of PreP in STD Clinics: High uptake and Drug detection among MSM in demonstration project.
CROI 2014. Abstract 954
PrEP Adherence: The Demo Project
• Sub-sample (n=87) had
blood samples to test
for presence of TFV-DP
at 4 weeks
• Majority had evidence
of taking at least 4
doses/week
Cohen et al. (2014). Implementation of PreP in STD Clinics: High uptake and Drug detection among MSM in demonstration project.
CROI 2014. Abstract 954
Oral PrEP Reduces Incidence of HIV in MSM, Even
With Incomplete Adherence
•
iPreX OLE: daily TDF/FTC oral PrEP
in MSM and transgender women (N
= 1603)
100% adherence was not required
to attain full benefit
from PrEP
– Benefit of 4-6 tablets/wk similar to
7 tablets/wk
– 2-3 tablets/wk also associated with
significant risk reduction
•
Higher levels of sexual risk taking at
baseline were associated with
greater adherence to PrEP
HIV Incidence and Drug Concentrations
HIV Incidence per 100 PersonYrs
•
5
4
<2
Tablets/
Wk
2-3
Tablets/
Wk
4-6 Tablets/Wk
3
7
Tablets/
Wk
Off PrEP
2
1
On PrEP
0
0 LLOQ
350 500
700
1000
TFV-DP in fmol/punch
Follow-up
26%
Risk Reduction 44%
95% Cl
-31 to 77%
12%
84%
21 to 99%
1250
1500
21%
12%
100%
100%
86 to 100% (combined)
1. Grant R, et al. IAC 2014. Abstract TUAC0105LB. 2. Grant R, et al. Lancet Infect Dis. 2014;14:820-829.
Event Driven Dosing…..
• IPERGAY
– 86% reduction in HIV infection
– Event-Driven Dosing (2 doses prior + 1 dose daily
for every day of sex+1 day after last exposure)
– (N=353)
• HIV Infections:
• 2 infections (PrEP) vs 14 (Placebo) @ 13 months
• 0.94/100 PY vs 6.6/100 PY (86% reduction, 95% CI:4499) p. = 0.002
Molina J-M et al. On Demand PrEP With Oral TDF-FTC in MSM: Results of the ANRS Ipergay Trial. CROI 2015
Conference Seattle. Abstract 23LB. 2015.
…..other factors
Provider level factors
• Adoption of new interventions
• System level factors
Provider attitudes & experience
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•
•
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Survey of ID physicians (n=573)
74% supported PrEP
9% have actually prescribed PrEP
14% would not provide PrEP
Karris et al. (2014). Clin Infec Dis 58(5). 704-12
.
Providers Perceived Barriers to PrEP
• Cost of PrEP
• Drug Resistance
• Reluctance to start a toxic drug in a healthy
person
• Efficacy of real world PrEP
• Time consuming
Karris et al. (2014). Clin Infec Dis 58(5). 704-12
.
Providers’ Concern regarding
Prescribing PrEP
Tellalian et al. AIDS Patient Care and STDs. October 2013, 27(10):.
No Evidence of Risk Compensation in iPrEx study
Marcus et al. PLoS One 2013
NPEP: LESSONS LEARNED
nPEP use and risk behavior
 Men who have sex with men from the
EXPLORE trial
 M=4,295 participants (6.3% used nPEP during
study)
 Conclusion:
 Availability of nPEP did not appear to lead to
increased sexual risk
Donnell, Mimiaga, et al. (2010). AIDS Behav 14:1182-1189.
Key facilitators of nPEP
impelementation
• Knowledge
• Risk perception, risk evaluation, and decision to
initiate prophylaxis
• Adherence
• Risk compensation and prevention synergy
• Access
Cohen et al. (2013). Am J. Prev Med 44(1S2)
Provider Attitudes & Beliefs
• Most effective way to decrease acquisition
of HIV infection?
– Expanded Testing
– Detection & treatment of STI
– Promotion of condom use
– Mental health & substance abuse counseling
– Community-based behavioral interventions
– PrEP
Tellalian et al. AIDS Patient Care and STDs. October 2013, 27(10):.
Provider Knowledge
• Survey of GW ID society & Armed Forced ID
society MDs (n=105)
• 60% of knowledge questions answered
incorrectly. (higher in those with >25% of time
doing HIV care)
• 67% felt current literature supports use of PrEP
• ? Restrict prescribing PrEP to those with HIV
experience
Wilson et al. Knowledge and perception of PrEP in two cohorts of Infectious Disease providers. Poster. IDWEEK 2014 (1522)
HIV PrEP & Person who Inject Drugs
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Provision of medications
Safety screening
Behavior interventions
Integration of PrEP into comprehensive care
Monitoring impact
Coverage & Access
• Insurance carriers are covering PrEP
– Prior authorization required by most companies
• Truvada for PrEP Assistance Program
• Insured & non-insured at 500% FPL = $58,344/year
• Benefit $300/mos (co-pays)
– Medication shipped to provider’s office
– Requires coordination between
patient/pharmacy/provider
ICD codes
• V01.79 (Z20.82)
– Contact or Exposure to other viral disease
• V01 (Z20.2)
– Contact with or exposure to communicable
disease
PrEP Line
CEI Clinician Inquiry Line
866-637-2342
UCSF Peer to Peer Consultation:
Clinician Consultation Center UCSF, HRSA/HAB, AETC
Mon-Fri 11 a.m. – 6 p.m. EST
855-448-7737
Successful Implementation
Characteristics of Successful PrEP Programs
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•
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•
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Clinical Expertise
Cultural competency
Outreach
Ongoing Quality Improvement
Regularly provider training
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•
•
Comprehensive Needs Assessment
Community/Consumer Involement
Stakeholder Buy-In
Engagement with Public Health System
•
•
•
•
•
•
Sustainability Planning
Infrastructure development
Ongoing Quality Improvement
Administrative management systems
Fiscal Management systems
Executive Leadership Support
Recommendations
•
•
•
•
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Assess needs of the community & target population
Engage community & Stakeholders
Develop partnerships
Provide necessary support services
Develop clinical, administrative, and fiscal
infrastructure
• Ensure capacity for prevention, follow-up, treatment
• Establish clear linkages for continuum of care
• Integrate all components to clients wherever they
enter prevention and care.
Trent-Adams & Cheever, (2013). Am J Prev Med; 44 (Is2)
PrEP – NY State Guidelines
• Follow-up and monitoring
includes prevention services
that are part of comprehensive
prevention plan, such as:
–
–
–
–
Risk reduction counseling
Access to condoms
STI screening
Mental Health & Substance Use
Screening, when indicated.
New York State Summary on Pre-Exposure Prophylaxis (2014). www.hivguidelines.org
Consider team-based approaches
Quality Indicators for PrEP Programs
• HIV Testing
– Baseline
– Every 3 months
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•
•
•
PrEP Prescriptions
Seroconversions
Seroconversions, resistant virus
STI testing
CDC Providers Supplement, 2014
U.S. Cities Involved in Demonstration
Projects
Seattle (2)
Detroit
Boston (2)
Rochester
NYC (2)
Newark
Philadelphia (2)
Baltimore
Bethesda
Annandale
Providence
Chicago (2)
San Francisco (2)
Oakland
Aurora
Cleveland
D.C.
Los Angeles (2)
Nashville Chapel Hill
San Diego
Memphis
Dallas
Jackson
Atlanta
Birmingham
New Orleans
Orlando
Houston(2)
Miami
Tampa
Demonstration and Implementation projects have a
planned enrollment of approximately 8,000 participants.
* NYC = Manhattan, Harlem, Bronx and Brooklyn
60
Implementation Pilot Studies
Benin
Senegal
Australia
Kenya
Nigeria
SA
India
Brazil
Zimbabwe
UK
Thailand
NIAID Demo: Miami, SF,
DC
East Bay CRUSH Oakland
LA PATH
CA ALERT: LA, Long
Beach, SD
CDC Demo (1200)
NYC SPARK
ATN (15 sites)
HPTN 073 DC LA Chapel
Hill
Improved
Testing
Behavioral
Interventions
Treatment
of HIV
ZERO NEW
INFECTIONS
Biomedical
Prevention
Policy &
Resource
Summary and Key Points
• As consumer awareness of PrEP increases,
providers should be prepared to offer
accurate information and/or offer referrals to
appropriate expertise
• Providers should continue to assess
candidates for PrEP and offer, if appropriate
• Organizations offering PrEP should assess
capacity, consider use of team-based care
QUESTIONS?
Contact Information
Jeffrey Kwong, DNP, MPH, ANP-BC
email: [email protected]
212-342-3765