Postexposure Prophylaxis (PEP)

NORTHWEST AIDS EDUCATION AND TRAINING CENTER
Postexposure Prophylaxis (PEP)
Hillary Liss, MD
Clinical Assistant Professor of Medicine, University of Washington
Medical Program Director, NW AETC
Last Updated: May 2014
Postexposure Prophylaxis (PEP)
§  2013 HIV Occupational PEP Guidelines
§  HIV Non-Occupational PEP (nPEP)
§  Management of Exposure to HBV and HCV
Estimated Prevalence of Chronic Viral Diseases
1.2 Million Persons Living with HIV
2.7-3.9 million Persons Living with HCV
0.8-1.4 Million Persons Living with HBV
*N = 1,106,400
(95% CI 1,056,400—1,156,400)
Source: Institute of Medicine. Hepatitis and Liver Cancer. Jan 2010.
HIV Occupational PEP
Case
A 45-year-old offender janitor working in Health Services is
cleaning behind a trash can and is stuck with a needle in the
hand.
The needle is hollow-bore with visible blood in the syringe
and on the needle.
He was wearing gloves but has a skin puncture and noticed
bleeding.
He washed the area thoroughly.
He has no past medical history.
Are you concerned about this exposure? What qualifies as
an exposure?
2013 USPHS Occupational PEP Guidelines
Infectious Fluids Involved in Exposure
Relative Risk of Infectious Fluids in Occupational Exposure to HIV
Category of Infectivity
Infectious Fluids
Fluid
•  Blood
•  Visibly bloody body fluids
Potentially Infectious
Body Fluids
• 
• 
• 
• 
• 
• 
• 
Semen and vaginal secretions
Cerebrospinal fluid
Synovial fluid
Pleural fluid
Peritoneal fluid
Pericardial fluid
Amniotic fluid
Not Considered Infectious
(unless visibly bloody)
• 
• 
• 
• 
Saliva, vomitus, and feces
Nasal secretions and sputum
Sweat and tears
Urine
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
2013 USPHS Occupational PEP Guidelines
At Risk Exposures
•  Contact of blood, tissue, or other potentially infectious
body fluids via:
- Percutaneous injury
- Mucous membrane exposure
- Contact with nonintact skin
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
Estimated Risk of HIV Transmission with Different Exposures
Risk of HIV Transmission in Health Care Workers
Type of Exposure to Blood
Risk of HIV Transmission
Percutaneous Exposure
0.3%
Mucous Membrane Exposure
0.09%
Nonintact Skin Exposure
< 0.09%
Source: CDC and Prevention. MMWR Morb Mortal Weekly Rep. 2001;50(RR-11):1-42.
Estimated Risk of Seroconversion with Percutaneous Injury
Seroconversion (%)
60
50
50
40
30
30
20
10
0.3
2
0
HIV
Hepatitis C
HBsAg+
HBeAg-
HBsAg+
HBeAg+
Source: CDC and Prevention. MMWR Morb Mortal Weekly Rep. 2001;50(RR-11):1-42.
Would you oﬀer this oﬀender HIV postexposure prophylaxis? A.  Yes, tenofoviremtricitabine
B.  Yes, tenofoviremtricitabine plus
raltegravir
C.  Yes, tenofoviremtricitabine plus
another ARV
D.  No, I would not offer
PEP in this situation
u s p u b l i c h e a l t h s e rv i c e g u i d e l i n e
Updated US Public Health Service Guidelines for the Management
of Occupational Exposures to Human Immunodeficiency Virus
and Recommendations for Postexposure Prophylaxis
2013
1
David T. Kuhar, MD; David K. Henderson, MD;2 Kimberly A. Struble, PharmD;3
Walid Heneine, PhD;4 Vasavi Thomas, RPh, MPH;4 Laura W. Cheever, MD, ScM;5
Ahmed Gomaa, MD, ScD, MSPH;6 Adelisa L. Panlilio, MD;1
for the US Public Health Service Working Group
This report updates US Public Health Service recommendations for the management of healthcare personnel (HCP) who experience
occupational exposure to blood and/or other body fluids that might contain human immunodeficiency virus (HIV). Although the principles
of exposure management remain unchanged, recommended HIV postexposure prophylaxis (PEP) regimens and the duration of HIV followup testing for exposed personnel have been updated. This report emphasizes the importance of primary prevention strategies, the prompt
reporting and management of occupational exposures, adherence to recommended HIV PEP regimens when indicated for an exposure,
expert consultation in management of exposures, follow-up of exposed HCP to improve adherence to PEP, and careful monitoring for
adverse events related to treatment, as well as for virologic, immunologic, and serologic signs of infection. To ensure timely postexposure
management and administration of HIV PEP, clinicians should consider occupational exposures as urgent medical concerns, and institutions
should take steps to ensure that staff are aware of both the importance of and the institutional mechanisms available for reporting and
seeking care for such exposures. The following is a summary of recommendations: (1) PEP is recommended when occupational exposures
to HIV occur; (2) the HIV status of the exposure source patient should be determined, if possible, to guide need for HIV PEP; (3) PEP
medication regimens should be started as soon as possible after occupational exposure to HIV, and they should be continued for a 4-week
duration; (4) new recommendation—PEP medication regimens should contain 3 (or more) antiretroviral drugs (listed in Appendix A) for
all occupational exposures to HIV; (5) expert consultation is recommended for any occupational exposures to HIV and at a minimum for
situations described in Box 1; (6) close follow-up for exposed personnel (Box 2) should be provided that includes counseling, baseline and
follow-up HIV testing, and monitoring for drug toxicity; follow-up appointments should begin within 72 hours of an HIV exposure; and
(7) new recommendation—if a newer fourth-generation combination HIV p24 antigen–HIV antibody test is utilized for follow-up HIV
testing of exposed HCP, HIV testing may be concluded 4 months after exposure (Box 2); if a newer testing platform is not available,
follow-up HIV testing is typically concluded 6 months after an HIV exposure.
Infect Control Hosp Epidemiol 2013;34(9):875-892
Source:
Preventing exposures to blood and body fluids (ie, primary important element of workplace safety. This document proprevention) is the most important strategy for preventing vides updated recommendations concerning the management
occupationally acquired human immunodeficiency virus of occupational exposures to HIV.
(HIV) infection.
healthcare providers
the
The use
of antiretrovirals as postexposure prophylaxis
Kuhar
DT, etBoth
al. individual
Infect Control
Hospand
Epidemiol.
2013;34:875-92.
institutions that employ them should work to ensure adher- (PEP) for occupational exposures to HIV was first considered
2013 USPHS Occupational PEP Guidelines
Challenges Addressed
•  Difficulties determining level of risk and determining
appropriateness of 2 versus 3-drug PEP
•  High rates of side effects and intolerability of previously
recommended ARV’s for PEP
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
2013 USPHS Occupational PEP Guidelines
Number of Antiretroviral Medications to Use
“As less toxic and better-tolerated medications for the
treatment of HIV infection are now available, minimizing
the risk of PEP noncompletion, and the optimal number
of medications needed for HIV PEP remains unknown,
the PHS working group recommends prescribing 3
(or more) tolerable drugs as PEP for all occupational
exposures to HIV.”
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
2013 USPHS Occupational PEP Guidelines
Reasons For Recommending 3-Drug PEP
•  Studies of 3-drug effectiveness for treating HIV
•  Concerns about possible resistance to agents used for PEP
•  Safety and tolerability of newer ARV’s
•  “Clinicians facing challenges such as medication availability,
adherence or toxicity issues…might still consider a 2-drug
regimen in consultation with an expert”
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
Percent of HCWs
Tolerability of HIV PEP in HCW
100
90
80
70
60
50
40
30
20
10
0
Incidence of Common Side Effects
Nausea
Fatigue Headache Vomiting Diarrhea Myalgias
Wang SA. Infect Control Hosp Epidemiol 2000;231:780-5.
2013 USPHS Occupational PEP Guidelines
Recommendations for Antiretroviral Regimens
Recommended Antiretroviral Regimens for Occupational PEP (28-Day Duration)
Preferred Regimen
INSTI
NNRTI
Raltegravir (Isentress) Tenofovir-Emtricitabine (Truvada)
400 mg twice daily
1 pill daily
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
Pill Burden
2013 USPHS Occupational PEP Guidelines
Recommendations for Antiretroviral Regimens
Alternative Antiretroviral Regimens for Occupational PEP (28-Day Duration)
INSTI, PI, or NNRTI
NNRTI
Alternative Regimens: Combine from both columns (listed in order of preference)
Raltegravir (Isentress)
Tenofovir-Emtricitabine (Truvada)
Darunavir (Prezista) + Ritonavir (Norvir)
Tenofovir (Viread) + Emtricitabine (Emtriva)
Etravirine (Intelence)
Tenofovir (Viread) + Lamivudine (Epivir)
Rilpivirine (Edurant)
Zidovudine-Lamivudine (Combivir)
Atazanavir (Reyataz) + Ritonavir (Norvir)
Zidovudine (Retrovir) + Lamivudine (Epivir)
Lopinavir-Ritonavir (Kaletra)
Zidovudine (Retrovir) + Emtricitabine (Emtriva)
Alternative Regimen: Fixed-Drug Combination
Elvitegravir-Cobicistat-Tenofovir-Emtricitabine (Stribild)
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
Effectiveness of Tenofovir (TDF) PEP in Macaques
SIV Inoculation
Study Hour
Study Features
N = 24 macaques
Randomized to 6 treatment arms
SIV inoculated intravenously
Start PEP
0
24 48 72
24h Placebo x 28d
24h TDF x 3d
24h TDF x 10d
SIV dose 10x 50% infective dose
PEP started at 24, 48, or 72 hours
24h TDF x 28d
PEP duration: 3, 10, or 28 days
PEP regimen: tenofovir (TDF) SQ
Analyzed for antibody and viremia
48h
72h
Source: Tsai CC, et al. J Virol. 1998;72:4265-73.
TDF x 28d
TDF x 28d
Effectiveness of Tenofovir PEP in Macaques
Persistent SIV Infection (%)
60
100
50
50
50
50
40
30
25
20
10
0
0
Placebo
Start @ 24h
Start @ 24h
Start @ 24h
Start @ 48h
Start @72h
3-Day Rx
10-Day Rx
28-Day Rx
28-Day Rx
28-Day Rx
Source: Tsai CC, et al. J Virol. 1998;72:4265-73.
Effectiveness of Tenofovir (TDF) PEP in Macaques
Conclusion: “These results clearly show that both the
time between virus exposure and initiation of tenofovir
treatment as well as the duration of treatment are crucial
factors for prevention of acute SIV infection in the
macaque model.”
Source: Tsai CC, et al. J Virol. 1998;72:4265-73.
2013 USPHS Occupational PEP Guidelines
Additional Key Points
•  PEP should be initiated as soon as possible after
exposure, preferably within hours
•  PEP should be provided for 28 days
•  Whenever possible, the HIV status of the source patient
should be determined, but should NOT delay starting PEP
•  An exposed individual should be advised to use
precautions (eg. barrier contraception, avoid blood
donations, pregnancy and, if possible, breast feeding)
during first 6-12 weeks after exposure
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
2013 USPHS Occupational PEP Guidelines
Situations for Which Expert Consultation Advised
•  Delayed exposure report (eg. longer than 72 hours)
•  Unknown source (eg. needle in sharps disposal)
•  Known or suspected pregnancy in exposed person
•  Exposed person breast-feeding
•  Known or suspected ARV drug resistance in source patient
•  Serious medical illness in exposed persons
•  Toxicity occurring in exposed person taking PEP regimen
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
Postexposure Prophylaxis Line (PEPline)
888-448-4911
What if the Source Patient has an Undetectable Viral Load?
•  A 32-year-old physician has a needlestick injury on her
hand that involves an HIV-infected patient. The source
patient is taking tenofovir-emtricitabine-efavirenz (Atripla)
and had an undetectable HIV RNA level 3 months prior.
•  Based on USPHS 2013 Guidelines, would you
recommend antiretroviral PEP for this physician?
Would you oﬀer PEP if the source pa;ent had an undetectable viral load when checked 1 month ago? A.  Yes B.  No 2013 USPHS Occupational PEP Guidelines
PEP when Source Patient has Undetectable HIV RNA Level
“Exposure to a source patient with an undetectable
serum viral load does not eliminate the possibility of
HIV transmission or the need for PEP and follow-up
testing. While the risk of transmission from an
occupational exposure to a source patient with an
undetectable serum viral load is thought to be very low,
PEP should still be offered.”
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
2013 USPHS Occupational PEP Guidelines
Baseline and Follow-Up for Occupational PEP
• Early Reevaluation after Exposure (within 72 hours)
• Baseline and Follow-up HIV Testing
- Baseline HIV testing
- Follow-up HIV testing 6, 12, and 24 weeks after exposure
- Follow-up HIV testing at 6 and 16 weeks if 4th generation assay* used
• Baseline and Follow-up Laboratory Testing
- Baseline renal and hepatic function tests
- Follow-up renal and hepatic function tests at 2 weeks
*4th generation combination assay = HIV p24 antigen-HIV antibody test
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
2013 USPHS Occupational PEP Guidelines
Summary of Major Changes
•  Eliminates evaluation of level of risk to stratify PEP
regimen; all regimens should contain 3 or more ARV’s
•  New recommended and alternative PEP regimens;
encourages regimens that are ‘optimally tolerated’
•  Follow-up may conclude at 4 months if 4th generation HIV
testing used
Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:875-92.
HIV Non-Occupational PEP (nPEP)
Case
Two offenders are caught engaging in anal sex without a
condom.
Although this falls under Prison Rape Elimination Act (PREA),
the officers believe it to be consensual, and bring the
offenders directly to segregation.
Medical incidentally finds out about the event the next day
and notes that one of the offenders has HIV.
His HIV RNA level is 2,340 copies/mL and he is not currently
taking ART.
What would you oﬀer the uninfected oﬀender for HIV PEP? A.  Tenofovir-‐emtricitabine B.  Tenofovir-‐emtricitabine plus raltegravir C.  Tenofovir-‐emtricitabine plus another ARV D.  Something else E.  I wouldn’t oﬀer PEP Estimated Per Act Risk for Acquisition of HIV,
by Exposure Route
Exposure Route
Per-act risk of transmission
Blood transfusion
90%
Needle-sharing IVDU
0.67%
Receptive anal intercourse
0.50%
Percutaneous needle stick
0.30%
Receptive penile-vaginal
intercourse
0.10%
Insertive anal intercourse
0.06%
Insertive penile-vaginal
intercourse
0.05%
Receptive oral intercourse
0.01%
Insertive oral intercourse
0.0005%
Source: CDC and Prevention. MMWR Morb Mortal Weekly Rep. 2005;54(RR-2).
Non-occupational PEP Algorithm
Adapted from MMWR January 21, 2005, Vol 54, No. RR-2. Reproduced from www.hivwebstudy.org
What is considered Substantial Risk?
•  Substantial Risk
•  Exposure of
-  Vagina, rectum, eye, mouth or
other mucous membrane,
nonintact skin, or percutaneous
contact
•  With
-  Blood, semen, vaginal
secretions, rectal secretions,
breast milk, or any body fluid
that is visibly contaminated with
blood
•  When
-  The source is known to be HIV
infected
•  Negligible Risk
•  Exposure of
-  Vagina, rectum, eye, mouth or
other mucous membrane, intact
or nonintact skin, or
percutaneous contact
•  With
-  Urine, nasal secretions, saliva,
sweat, or tears if not visibly
contaminated with blood
•  Regardless
-  Of the known or suspected HIV
status of the source
Recommended Lab Evaluation for HIV nPEP
Baseline
During nPEP 4-6 Wks
HIV Antibody
E, S
E
CBC with differential
E
E
LFTs
E
E
BUN/Cr
E
E
STD screen
E, S
E
3 Mos
E
6 Mos
E
E
(GC/CT/RPR)
Hep B serology
E, S
Hep C serology
E, S
Pregnancy test
E
HIV viral load/CD4 cells
S
HIV resistance testing
S
E
E
E
E
E
E
E
E
E
E
E
E
2-Drug vs. 3-Drug ART for nPEP
“The recommendation for a three-drug HAART regimen is based on
the assumption that the maximal suppression of viral replication
afforded by HAART will provide the best chance of preventing
infection in a person who has been exposed.”
“Clinicians and patients who are concerned about potential adherence
and toxicity issues associated with a three-drug HAART regimen
might consider the use of a two-drug regimen.”
Source: CDC and Prevention. MMWR Morb Mortal Weekly Rep. 2005;54(RR-2).
Tenofovir-Emtricitabine (TDF-FTC) plus Raltegravir
for nPEP
Mayer et al, JAIDS, 2012
•  100 participants enrolled at Fenway Health
-  98% male, 83% MSM, mean age 33
•  Prescribed TDF-FTC plus raltegravir for nPEP
•  85 had 3-months follow-up
•  57% finished the regimen as prescribed
-  Comparable to historic controls (AZT-3TC or TDF-FTC + PI/r)
-  Biggest limitation = missed second dose of raltegravir by 27%
•  Well tolerated and fewer side effects than historic controls
Mayer K, et al. J Acquir Immune Defic Syndr. 2012;59(4):354-359.
Other Reminders Regarding nPEP
•  Remember possible reverse exposure
-  Sexual assault victim may have HIV or other transmissible infection
-  Evaluate all involved offenders
-  Remember to screen for STDs
•  Human bites and altercations may lead to exposure
-  “For human bites, clinical evaluation must include the possibility that
both the person bitten and the person who inflicted the bite were
exposed to bloodborne pathogens”
HCV Occupational PEP
An oﬀender and his cellie are found with new taOoos and the cellie has known HCV. Would you oﬀer HCV PEP? A.  Yes B.  No Postexposure Prophylaxis for HCV
HCW with Exposure to HCV (+ ) Source
No Postexposure Prophylaxis Recommended
Source: CDC. MMWR Morb Mortal Weekly Rep. 2001;50(RR-11):1-42.
Pilot Study of Postexposure Prophylaxis with Peginterferon
for Hepatitis C Virus in Health Care Workers
HCW with Exposure to HCV (+ ) Source
(n = 213)
HCW who Participated in PEP Protocol
(n = 51)
High-Risk Exposure
Low Risk Exposure
(n = 25)
(n = 26)
PEP
No PEP
PEP
No PEP
(n = 21)
(n = 4)
(n =23)
(n = 3)
PEP = Peginterferon alpha-2b (1.0 ug/kg subcutaneously) once weekly x 4 weeks
Source: Corey KE, et al. Infect Control Hosp Epidemiol. 2009;30:1000-5.
Pilot Study of Postexposure Prophylaxis with Peginterferon
for Hepatitis C Virus in Health Care Workers
•  Summary of Results
-  29
(66%) of 44 completed 4-week course of Peginterferon
-  None of 44 who randomized to PEP had HCV seroconversion
- None of 169 HCW who did not receive PEP had HCV
seroconversion
Source: Corey KE, et al. Infect Control Hosp Epidemiol. 2009;30:1000-5.
Pilot Study of Postexposure Prophylaxis with Peginterferon
for Hepatitis C Virus in Health Care Workers
“On the basis of these findings and given the low frequency
of transmission, the high adverse event rate and impaired
quality of life, and the effectiveness of peginterferon alfa-2b
for acute HCV infection, we do not recommend routine
postexposure prophylaxis with peginterferon alfa-2b for
occupational exposures.”
Source: Corey KE, et al. Infect Control Hosp Epidemiol. 2009;30:1000-5.
Possible Future Oral PEP for Hepatitis C Exposure
NS3A/4A Protease Inhibitor
Nucleoside Analogue
Nucleotide Analogue
Non-Nucleoside Analogue
Non-Nucleotide Analogue
NS5A Inhibitor
$$$$
Well-tolerated, oral
treatments with high
cure rates available or
coming soon!
Follow-Up for Exposure to Hepatitis C
•  Baseline: anti-HCV and ALT
•  Follow-up testing (at 4-6 months) for anti-HCV and ALT activity
•  Consider HCV RNA testing at 4-6 weeks if earlier diagnosis
desired
•  Confirm all anti-HCV results reported by enzyme immunoassay
with supplemental test
Source: CDC and Prevention. MMWR Morb Mortal Weekly Rep. 2001;50(RR-11):1-42.
HBV Occupational PEP
Postexposure Prophylaxis for Hepatitis B
Previously HBV-Vaccinated, Unknown Response
HBV Exposure
Check HBsAb Titer
HBsAb > 10 mIU/ml
HBsAb <10 mIU/ml
No Treatment
1 Dose HBIG (.06 ml/kg),
1 Vaccine Booster Dose
Source: CDC. MMWR Morb Mortal Weekly Rep. 2001;50(RR-11):1-42.
Postexposure Prophylaxis for Hepatitis B
Previously HBV-Vaccinated, Known Response*
HBV Exposure
No Treatment
*Known HBsAb ≥ 10 mIU/ml after HBV Immunization
Source: CDC. MMWR Morb Mortal Weekly Rep. 2001;50(RR-11):1-42.
Postexposure Prophylaxis for Hepatitis B
Previously HBV-Vaccinated, No Response*
HBV Exposure
1 Dose HBIG (.06 ml/kg),
Repeat HBIG in 1 Month
or
1 Dose HBIG (.06 ml/kg),
Vaccine Series
*Failed to respond to HBV vaccine series
Source: CDC. MMWR Morb Mortal Weekly Rep. 2001;50(RR-11):1-42.
Postexposure Prophylaxis for Hepatitis B
Previously HBV-Vaccinated, No Response*
HBV Exposure
Lamivudine?
Entecavir?
Tenofovir?
*Failed to respond to HBV vaccine series
Hepatitis B Virus: Natural History after Infection
95%
95%
Neonatal HBV Infection
30%
30%
Childhood HBV Infection
5%
5%
Adult HBV Infection
Source: Lee WM. N Engl J Med 1997;337:1733-45.
Chronic HBV Infection
PEP Update Summary
•  HIV occupational PEP guidelines updated in 2013 emphasize
early initiation of 3-drug PEP with well-tolerated ARV’s and
potential shortened follow-up course with 4th generation Ag/Ab
assay testing
•  PEP is recommended for both occupational & non-occupational
HIV exposures
•  No antivirals currently recommended for HCV PEP; well-tolerated
treatments are available or coming soon
•  HBV PEP depends on risk of exposure, previous vaccination and
known or unknown vaccine response
Questions
Feel free to email:
[email protected]

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