Download Pre-Exposure Prophylaxis brief overview

HIV Prevention 2016
John Leander Po, MD, PhD
Infectious Disease Fellowship Program Director
Associate Professor of Clinical Medicine
University of Arizona
Cesar Egurrola, Clinical Coordinator
Petersen HIV Clinics
University of Arizona
Special thanks:
Mayar Al Mohajer, MD FACP
Medical Director, Antibiotic Stewardship Program
Associate Professor of Clinical Medicine
University of Arizona
Disclosures
AETC- PEP & PrEP
 I have no financial relationships to disclose.
 PrEP Navigator Model discussed in this presentation
is specific to the Navigator component and
experiences at Petersen HIV Clinics.
Michael
 You are evaluating a 23 year-old male at your office for a
primary care visit
 He has no active complaints. He is sexually active with men and
had six partners over the past year
 He has a history of syphilis diagnosed two-years ago and was
treated with IM penicillin
 Six months ago, you counseled him on the importance of
consistent condom use
 He reports that he currently uses condoms ~80% of the time.
No recent STD since last visit. He drinks alcohol occasionally
and no illicit drug use
What would you recommend for
Michael?
1. HIV screening
2. HIV and STD screening
3. HIV, STD screening and discuss
the importance of persistent
condom use
4. Offer daily Truvada (TDF/FTC)
plus HIV, STD screening and
discuss the importance of
consistent condom use
33%
33%
33%
0%
1.
2.
3.
4.
Understanding PrEP
Example: Birth Control Pill
Oral Contraceptive
(“The Pill”)
Pre-Exposure Prophylaxis
(PrEP)
Prevents pregnancy if taken before sex. Does
not work as morning-after pill.
Prevents HIV infection pre-exposure. Will not
work if already exposed.
Does not always start working immediately.
Does not start working immediately.
Must take daily – cannot skip doses.
Must take daily – cannot skip doses.
Only helps prevent pregnancy, will not prevent
STIs (should still use condoms).
Only helps prevent HIV – will not prevent other
STIs (should still use condoms).
Very effective at preventing pregnancy, but not
100% effective.
Very effective at preventing HIV infection, but
not 100% effective.
Should be taken by anyone who is sexually
active (at risk for becoming pregnant)
Should be taken by anyone who could be
exposed to the HIV virus (at risk for HIV)
If PrEP is taken daily, it can reduce sexually
acquired HIV infection by up to…
33%
1.
2.
3.
4.
33%
33%
50-60%
60-80%
80-90%
>90%
0%
1.
2.
3.
4.
I feel that patients on PrEP will…
67%
1. Increase their risk behavior
2. Decrease their risk
behavior
3. No change in behavior
4. I don’t know
33%
0%
1.
2.
0%
3.
4.
Which statement best applies to you?
1. I have not prescribed PrEP
2. I have prescribed PrEP for 1-5 patients
3. I have prescribed PrEP for >5 patients
67%
33%
0%
1.
2.
3.
For those who said they have not
prescribed PrEP, was it because…
1.
2.
3.
4.
I need more information about PrEP
It takes too much time
None of my patients could afford it
33%
Other
67%
0%
1.
2.
0%
3.
4.
My top concern about PrEP is…
1.
2.
3.
4.
5.
6.
7.
Not enough research on long
term effects of PrEP
Financial concerns – who is
paying for it?
STDs will increase due to
increase in risk behavior
Patients will not be adherent
Not enough education for
providers
On demand PrEP is not
effective in women
Other
67%
33%
1.
2.
0%
0%
0%
0%
0%
3.
4.
5.
6.
7.
Only Infectious Disease Specialists can
prescribe anti-viral medications
1. True
2. False
3. Don’t know
67%
33%
0%
1.
2.
3.
PrEP Navigators
 Individuals based out of provider’s office or
community organizations linked to providers, whose
main role is to facilitate access to PrEP.
 PrEP navigation is “A comprehensive and systemwide approach is necessary to ensure that HIVnegative persons at risk of being exposed to HIV are
effectively linked to and managed on PrEP”- California
Department of Public Health
PrEP Navigators
 Provides basic PrEP Information and education
 Locate, and sometimes link to PrEP Providers
 Teaches patients how to utilize public and private
insurance to access PrEP (insurance navigation)
 Explains and explores Patient Assistance programs
for Truvada
 Helps uninsured or underinsured patient navigate
insurance options
 Links to community based clinic if uninsurable
PrEP Navigator- Education
 Provide accurate information about PrEP intervention
based on CDC PrEP Guidelines.
 Review PrEP care process.
 Provide PrEP education around importance of
adherence to medication and PrEP care plan, as well
as follow ups.
 Empower patient to self advocate for PrEP care as
needed.
 Answer any questions concerns patient might have
before starting PrEP
How does PrEP work?
Pre-Exposure Chemoprophylaxis for HIV Prevention
in Men Who Have Sex with Men- The iPrEX Trial
 Randomized clinical trial- 4905
subjects
 Truvada (TDF/FTC) was shown
to decrease the risk of HIV
transmission by 42% in MSM
who also received
comprehensive preventive
services
 The risk was decreased by 92%
in patients with detectable
drug levels
Grant RM, et al. N Engl J Med 2010;363:258799
PRE-EXPOSURE CHEMOPROPHYLAXIS FOR HIV PREVENTION IN
MEN WHO HAVE SEX WITH MEN- THE IPREX TRIAL
Grant RM et al. N Engl J Med 2010;363:2587-2599.
Sexual behavior by perceived treatment group
Marcus JL, Glidden DV, Mayer KH, Liu AY, et al. (2013) No Evidence of Sexual Risk Compensation in the iPrEx Trial of Daily
Oral HIV Preexposure Prophylaxis. PLoS ONE 8(12): e81997. doi:10.1371/journal.pone.0081997
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081997
Antiretroviral Prophylaxis for HIV Prevention in
Heterosexual Men and Women- The PartnersPrEP Trial
 Truvada (TDF/FTC) was shown to decrease
the risk of HIV transmission by 75% in
uninfected individuals in stable
heterosexual serodiscordant relationship
who also received comprehensive
preventive services
 Tenofovir alone decreased the risk by 67%.
 The risk was decreased by 90% in patients
with detectable TDF and FTC levels
 8 patients were infected with HIV before
randomization. Resistant HIV to the study
medications developed in 2 cases
 No participants who acquired HIV after
randomization developed resistance
BAETEN JM ET AL. N ENGL J MED 2012;367:399410.
On-Demand Preexposure Prophylaxis in Men at
High Risk for HIV-1 Infection
 Randomized clinical trial- 414
subjects
 Truvada (TDF/FTC) before and
after sexual activity was
shown to decrease the risk of
HIV transmission by 86% in
MSM who also received
comprehensive preventive
services
 Median of 15 pills/ month
Molina JM, et al. N Engl J Med 2015; Dec
3;373(23):2237-46
FDA Approval
Indications:
 On May 14, 2014, the US Public Health Service and the CDC
released the first comprehensive guidelines for PrEP.
 PrEP is indicated in patients who are HIV-negative and have one of
the following risk factors:
1. HIV-positive partners
2. MSM with recent unprotected sex or STD
3. Intravenous drug users (IDU) who reported sharing needles or
equipment, or have recently starting substance use treatment
program (high-risk for relapse).
4. Heterosexual men or women who infrequently use condoms and
have sex with high-risk partners
Estimated percentages and numbers of adults with
indications for preexposure prophylaxis (PrEP), by
transmission risk group — United States, 2015
MSM
Indicated for PrEP
IDU
Not Indicated for PrEP
Indicated for PrEP
Not Indicated for PrEP
Indicated for PrEP
Not Indicated for PrEP
115,0…
492,…
1,499,90
3, 75%
HETEROSEXUAL
624,…
506,600,
81%
156,000,000
99.60%
1 in 4
1 in 5
1 in 200
Centers for Disease Control and Prevention (2015) Vital Signs: Estimated Percentages and Numbers of Adults with Indications for Preexposure
Prophylaxis to Prevent HIV Acquisition — United States, 2015. Morbidity and Mortality Weekly Report, 64(46);1291-1295.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6446a4.htm
Case Continued:
You decided to start Michael on PrEP. What
tests should you order next?
1.
2.
3.
4.
HIV testing, hepatitis B antigen and Cr clearance
HIV testing, CD4, liver function test and Cr clearance
HIV testing, liver function testing, and Cr clearance
HIV testing, CD4 and liver function testing
33%
33%
33%
0%
1.
2.
3.
4.
Testing
 HIV testing, hepatitis B antigen and Cr clearance are
key tests before starting PrEP
 Other tests include:
STD panel (RPR, GC/CD)
Hepatitis A serology in MSM (for immunity)
Hepatitis B serology (for immunity)
Hepatitis C serology
Pregnancy testing (in women)
How often should you repeat HIV testing?
1.
2.
3.
4.
Every 30 days
Every 3 months
Every 6 months
Once a year
100%
1.
0%
0%
0%
2.
3.
4.
Are there signs or symptoms of HIV-1 infection, OR is recent
exposure to HIV suspected?
No
Yes
Do not initiate PrEP. Wait
1 month to ensure HIV-1
has not been contracted.
or
Confirm that HIV-1 has not
been contracted using a
highly sensitive, FDAapproved test. If
appropriate, consider
prescribing PrEP
Confirm negative HIV-1 status. If
appropriate, consider prescribing PrEP.
Re-confirm negative HIV-1 status at least every 3 months
Reducing HIV Risk Behaviors
 Trusting and confidential environment
 Ongoing dialogue with the patient regarding their risk
behavior
 PrEP is not always effective in preventing HIV infection
particularly if used inconsistently
 Consistent use of PrEP together with other prevention
methods (consistent condom use, discontinuing drug
injection or never sharing injection equipment) confers
very high levels of protection
PCH- Risk Factor Breakdown
HIV Risk Factors
MSM
11%
27%
22%
12%
3%
25%
MSM- Multiple Partners &
Inconsistent Condom Use
MSM- Inconsistent
Condom Use
MSM- No Condom Use
MSM- HIV + Partner
Heterosexual- HIV +
Partner
Beginning PrEP Medication Regimen
 Prescribe 1 tablet of Truvada (TDF [300mg] plus FTC
[200mg]) daily.
 In general, prescribe no more than a 90-day supply,
renewable only after HIV testing confirms that patient
remains HIV-uninfected.
 Provide risk-reduction and PrEP medication adherence
counseling and condoms.
http://www.cdc.gov/hiv/pdf/PrEPguidelines2014.pdf
PrEP Navigator- Benefits
Coordination
 Provide patient with estimate on PrEP cost, based on
their insurance plan
 Benefits Summary (medical visits, lab work)
 Formulary (medication)
 Find providers who work with patient’s specific
insurance plan
 Assist patient with prior authorization and appeals if
necessary.
 Link patient to PAP if necessary.
Case Continued: Michael
(without PrEP Navigator)
Michael goes to his local pharmacy to fill his prescription. The
pharmacist tells him he has $500 copay. Michael cannot afford
this copay. What do you think Michael will do next?
1.
Call Native Health and leave a message for his
provider letting them know he cannot afford
his prescription
2. Put the co-pay on his credit card
3. Nothing. Michael’s PrEP journey ends at the
pharmacy
4. Other
100
%
0%
1.
2.
0%
0%
3.
4.
Michael: Case Continued
(with Navigator)
Prior to going to the pharmacy, Michael speaks with the Native Health PrEP
navigator who educates him on patient assistant options. When he goes to
his local pharmacy , the pharmacist tells him he has $500 copay. Michael
cannot afford this copay. What do you think Michael will do next?
1.
2.
3.
4.
5.
Self advocate – talk to pharmacist about patient
assistance options
Call navigator for assistance.
33%
33% 33%
Access patient assistance option on his own.
Go to a different pharmacy recommended by
Native Health
0%
0%
Other
1.
2.
3.
4.
5.
Truvada Patient AssistanceGILEAD’s co-pay card
 Works with commercial insurance plans only and covers copays for medication.
 Federal insurance plans, such as Medicare, Medicaid, VA,
Tricare or Federal Employee Health Plans are not eligible.
 Covers $3,600 maximum per calendar year.
 No income restrictions.
 Yearly enrollment required.
 Covers co-pays, deductible and coinsurance.
 To apply visit www.gileadcopay.com or call 877-505-6986
Truvada Patient AssistanceGILEADS’s Advancing Access
 Works with commercial insurance plans only.
 Federal insurance plans, such as Medicare, Medicaid, VA, Tricare
or Federal Employee Health Plans are not eligible.
 Covers the whole amount of medication co-pay.
 Income based program, recipients income must be less than
500% FPL (<$59,400/year).
 Application, with provider signature, required.
 Proof of Income and Proof or Residency required with
application.
 Re-apply as needed.
 Covers co-pays only.
 To apply visit www.gileadadvancingaccess.com or call 800-2262056
Truvada Patient AssistancePatient Advocate Foundation (PAF)
 Works with all insurances
 Covers $5,000 maximum per year.
 Income based programs, recipient’s income must be
less than 400% FPL (<$47,520/year).
 Re-apply as needed.
 Covers co-pays only.
 To apply visit www.copays.org/diseases/hiv-aids-andprevention or call 800-532-5274
Provider-Pharmacy Collaborations
 Encouraged for adherence and easier access to
medication
 Provider identifies two or more pharmacies and forge
a collaboration for easier access to Truvada
 Increased communication
 Faster access to medication
 Increased adherence
CDC Guideline:
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+
CDC. PrEP Guideline. 2014
After 3 Mos and at
Least Every 6 Mos
Thereafter
 Assess renal
function
At Least Every
6 Mos
At Least Every 12
Mos
 Test for bacterial
STIs
 Evaluate need to
continue PrEP
 HBV DNA by quantitative assay* (every
6-12 mo)
PrEP in Clinical Practice: 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
Providers
• Unaware of intervention
• Uncertain how to deliver the
intervention
• Wary of complexity and time
involved
• Uninsured or unable to pay
• Adherence challenges
• Discomfort with assessing
candidacy
• Concern about disclosure
and stigma
• Uncertain how to bill for
intervention
PHC- PrEP Insurance Breakdown
Insurance Breakdown
Private/Commercial
47
Medicaid
15
Medicare
Insurance Breakdown
2
0
10
20
30
40
50
Stopping PrEP
 Reasons to stop PrEP:
 Evidence of HIV infection
 Pregnancy
 Adverse events
 Chronic non-adherence
 Patient choice
 On Discontinuing PrEP: Hepatitis B antigen, HIV
 If resuming PrEP after stopping, repeat standard pre-PrEP
evaluation
On-Demand Preexposure Prophylaxis in Men at
High Risk for HIV-1 Infection
 Randomized clinical trial414 subjects
 Truvada (TDF/FTC) before
and after sexual activity
was shown to decrease the
risk of HIV transmission by
86% in MSM who also
received comprehensive
preventive services
 Median of 15 pills/ month
Molina JM, et al. N Engl J Med 2015; Dec
3;373(23):2237-46
Future directions of PreP
 Why single dosing of PreP is not effective in women?
 Other drug delivery systems
 Alternative antiretrovirals for PreP
Women: Single dose PreP not as effective
Garrett KL, and others, CROI 2016, Boston, MA
Women might need to be more adherent than MSM
Percent of Women Achieving Effective Drug Concentrations in CD4+ Cells
Pharmacokinetics in 49 healthy female volunteers
Rectal Tissue
2-7 doses/week (28% adherence)
protects colorectal tissue
Cottrell ML et al, J Infect Dis 2016
Female Genital Tract Tissue
6-7 doses/week (85% adherence) to
protect female genital tract tissue
Single dosing of TDF: not enough
drug in CVF
Garrett KL, and others, CROI 2016, Boston, MA
New data on PrEP - 2016
 MTN-020/ASPIRE & IPM-027: Efficacy and Safety of
Dapivirine Vaginal Ring. Protection 27-37%
 ÉCLAIR: Cabotegravir LA (injectable) in HIV-Negative
Men at Low Risk for HIV Infection
 HPTN-069/A5305: Maraviroc-Based PrEP for MSM
PrEP Start-Up Kit
 Created by PHC staff to provide support for providers
interested in starting PrEP care at their practices. It
includes:




PrEP Provider Guide (AETC)
PrEP intake form (PHC)
PrEP Flow Chart (Project Inform)
Medication Assistance Program Application(GILEAD)
Conclusions
 PrEP is recommended as one prevention option for sexually active MSM,
heterosexual men and women, IDU at substantial risk of HIV acquisition
 Adherence is a key factor in PrEP efficacy
 Before prescribing PrEP, HIV infection must be excluded, and the patient
should be assessed for comorbidities that may present health risks
 The recommended PrEP regimen is fixed-dose TDF/FTC
 Patient assistance options are available to help patients afford PrEP.
 Patients prescribed PrEP should return for follow-up visits at least every
3 months
Questions
Training Evaluation
 Please complete an
online evaluation, at:
http://tinyurl.com/Nov30Eval
Josh
 Josh is a 28-year-old male who is presenting to your office
for an urgent visit
 He reported that he was having sex with a guy the night
before without a condom (insertive anal)
 He is concerned that the guy has not been tested for HIV
before
 Josh was tested for HIV three months ago and the result
was negative
 He uses condoms most of the times except when he drinks
alcohol
What is the best next step?
1. Avoid prescribing PEP since the patient
did not have unprotected receptive anal
intercourse
2. Place a STAT order for infectious disease
consultation so the patient can be seen
within a week
3. Prescribe PEP immediately
4. Repeat HIV testing in 2 weeks (window
period). If test is negative, then prescribe
PEP
0%
0%
0%
0%
1.
2.
3.
4.
Exposure Risks
(average, per episode, involving HIV-infected source patient)
Percutaneous (blood)
Mucous membrane exposure
0.3%
0.09%
Receptive anal intercourse
0.3 - 3%
Insertive anal intercourse
0.06%
Receptive vaginal intercourse
0.1 – 0.2%
Insertive vaginal intercourse
0.03 – 0.14%
Receptive oral (male)
Female-female orogenital
IDU needle sharing
Vertical (no prophylaxis)
0.06%
4 case reports
0.67%
24%
Risk of Infection
 Blood and visibly bloody body fluids
 Semen, vaginal secretions, cerebrospinal fluid,
synovial fluid, pleural fluid, peritoneal fluid,
pericardial fluid, and amniotic fluid
 Feces, nasal secretions, saliva, sputum, sweat,
tears, urine, and vomitus are not considered
potentially infectious unless they are visibly
bloody
Initiating PEP
 If the decision is made to administer post-exposure prophylaxis,
it should be started as early as possible after an exposure, ideally
within 2 hours
 Post-exposure prophylaxis is not indicated if the patient presents
for care more than 72 hours after an exposure
 HIV testing (serology and RNA) should be performed at baseline
 Before offering post-exposure prophylaxis, patients should also
be evaluated for the following criteria:
•
•
•
•
•
the nature of the exposure
whether the HIV status of the source is known
whether the exposure occurred within 72 hours prior to presentation
whether the patient is committed to future risk reduction
New York State Department of Health Guidelines 2014
What is the recommended PEP
regimen?
1.
2.
3.
4.
Zidovudine/lamivudine plus boosted darunavir
Tenofovir/emtricitabine plus raltegravir
Tenofovir/emtricitabine
Zidovudine/lamivudine plus boosted lopinavir
0%
0%
0%
1.
2.
3.
0%
4.
 Tenofovir + emtricitabine [Truvada] (QD) plus either
raltegravir (BID) or dolutegravir (QD) are recommended as
the preferred initial PEP regimen because of:
• its excellent tolerability
• proven potency in established HIV infection
• ease of administration
 Zidovudine and efavirenz are no longer recommended in the
preferred PEP regimen because of significantly high rates of
treatment-limiting side effects
PEP treatment should be continued for __days. HIV
testing should be repeated at __ weeks and __ months.
1.
2.
3.
4.
28 days; 4 weeks and 3 months
28 days; 4 weeks and 6 months
42 days; 4 weeks and 3 months
42 days; 4 weeks, and 6 months
0%
0%
0%
0%
1.
2.
3.
4.