Transcript Guidelines for the Use of Antiretroviral Agents in Adults

Guideline Summary
Updated US Public Health Service Guidelines for the
Management of Occupational
Exposures to HIV and Recommendations
for Postexposure Prophylaxis
Published August 2013
AETC NRC Slide Set
About This Presentation
These slides were developed using the September 2013
updated guidelines on postexposure prophylaxis (PEP)
following occupational exposure to HIV. The intended
audience is clinicians involved in the care of health care
personnel (HCP) with occupational exposure to HIV.
Users are cautioned that, because of the rapidly changing
field of HIV care, this information could become out of date
quickly. Finally, it is intended that these slides be used as
prepared, without changes in either content or attribution.
Users are asked to honor this intent.
– AETC NRC
2
August 2013
www.aidsetc.org
Updated Guidelines for the
Management of Occupational
Exposures to HIV
and Recommendations for
Postexposure Prophylaxis
Developed by the Public Health Service
Interagency Working Group, convened by
the CDC
3
August 2013
www.aidsetc.org
Guidelines Outline
 Principal changes from previous PEP
guidelines
 Health care personnel and exposure
 Risk of occupational transmission of HIV
 ARV toxicities and interactions
 Selection of HIV PEP regimens
 Resistance to ARVs
 ARV drugs during pregnancy and lactation
 Management by emergency physicians
4
August 2013
www.aidsetc.org
Guidelines Outline (2)
 Recommendations for the management of
HCP potentially exposed to HIV
 HIV PEP
 Source patient testing
 Timing and duration of PEP
 Selection of PEP drugs
 Follow-up of exposed HCP
 Postexposure testing
 Monitoring and management of PEP toxicity
5
August 2013
www.aidsetc.org
What the Guidelines Emphasize
 Prompt management of occupational
exposures
 Selection of effective and tolerable PEP
regimens
 Potential toxicities and interactions of PEP
drugs
 Consultation with experts for postexposure
management strategies
 Counseling and follow-up of exposed
personnel
6
August 2013
www.aidsetc.org
Principal Changes from Previous PEP
Guidelines
 Elimination of risk stratification for exposure
incidents
 3-drug (or more) PEP regimen for all
 Expanded list of ARVs for PEP
 Emphasis on tolerability and convenience of
PEP regimen
 New recommendations for follow-up HIV
testing
7
August 2013
www.aidsetc.org
Health Care Personnel: Definition
 HCP: all paid and unpaid persons working in
healthcare setting who have the potential for
exposure to infectious materials
8
August 2013
www.aidsetc.org
Occupational Risk Exposures in HCP
 Percutaneous injury
(needlestick, cut)
OR
 Contact of mucous
membrane or
nonintact skin
9
WITH:
• Blood
• Tissue
• Other body fluids that
are potentially infectious
(cerebrospinal, synovial,
pleural, pericardial,
peritoneal, or amniotic
fluids; semen or vaginal
secretions)
August 2013
www.aidsetc.org
NOT Considered Infectious for HIV
Unless Visibly Bloody




10
Feces
Nasal Secretions
Saliva
Sputum




Sweat
Tears
Urine
Vomitus
August 2013
www.aidsetc.org
Risk of Occupational Transmission of HIV
 Following percutaneous exposure:
approximately 0.3%
 Following mucous membrane exposure:
approximately 0.09%
 Risk following nonintact skin exposure
estimated to be <0.09%
 Risk following exposure to fluids or tissues
other than HIV-infected blood estimated to
be “considerably lower” than for blood
exposure
11
August 2013
www.aidsetc.org
Factors Associated with Increased Risk
 Visible contamination of device (such as
needle) with patient’s blood
 Needle having been placed directly into vein
or artery
 Hollow-bore (vs solid) needle
 Deep injury
 Source patient with terminal illness
 High viral load*
* Risk of transmission via occupational exposure to a source
patient with undetectable viral load is thought to be very low but
not impossible; PEP should be offered.
12
August 2013
www.aidsetc.org
Toxicity of PEP Regimens
 PEP should be taken for a full 4 weeks
 Substantial proportion of HCP taking earlier ARVs
as PEP did not complete full course of PEP
 Side effects of ARV drugs are common, and a
major reason for not completing PEP regimens
 Regimens that are tolerable for short-term use
should be selected
 Potential side effects should be discussed, and
treatment for anticipated side effects should be
prescribed preemptively, if indicated
13
August 2013
www.aidsetc.org
Interactions of ARV Agents
 ARVs can have serious interactions with other
drugs
 Before prescribing PEP, carefully evaluate
concomitant medications, including over-thecounters, supplements, and herbals
 Consult package inserts or other resources on ARV
drug-drug interactions; consult with experts
 Avoid interacting drugs and monitor carefully, as
appropriate
14
August 2013
www.aidsetc.org
Selection of HIV PEP Regimens: Rationale
for Current Recommendations
 Guidelines recommend use of ≥3 ARVs for
treatment of HIV infection
 Optimal number of ARVs needed for HIV PEP is
unknown
 Newer ARVs are better tolerated and have
better toxicity profiles than agents previously
used for PEP
 Thus, PEP regimens comprising 3 (or more)
tolerable ARVs now recommended for all
occupational exposures to HIV
15
August 2013
www.aidsetc.org
Selection of HIV PEP Regimens: Rationale
for Current Recommendations (2)
 To encourage HCP to complete the PEP
regimen:
 Optimize side effect and toxicity profiles
 Optimize dosing convenience
16
August 2013
www.aidsetc.org
Resistance to ARVs
 Resistance of the source virus to ARVs, particularly to
1 or more that may be included in a PEP regimen,
may reduce PEP efficacy
 Occupational transmission of drug-resistant HIV strains,
despite PEP, has been reported
 If source patient is known or suspected to harbor drugresistant HIV, consult with experts for PEP selection
 Do not delay initiation of PEP; use ARVs to which the source
virus is unlikely to be resistant
 Resistance testing at time of exposure is not practical, given
length of time required for results
 If resistance test results become available during PEP,
consider possible modification of PEP regimen if indicated
17
August 2013
www.aidsetc.org
ARVs during Pregnancy and Lactation
 Decision to offer PEP based on same
considerations as in other HCP
 Risk of HIV transmission during pregnancy or
breast-feeding is markedly increased in acute
HIV infection
 Potential risks of ARVs for pregnant women,
fetuses, and infants
 Expert consultation recommended in all cases
18
August 2013
www.aidsetc.org
ARVs during Pregnancy and Lactation (2)
 Potential toxicities of ARVs during pregnancy
and lactation depend on timing and duration of
exposure, and on number and type of ARVs
 Special considerations during pregnancy
 Efavirenz: 1st-trimester exposure may increase risk of
CNS defects
 Avoid efavirenz during 1st trimester
 If efavirenz-based PEP is used, do pregnancy test to rule out
early pregnancy; counsel nonpregnant women to avoid
pregnancy until after completing PEP
 Stavudine + didanosine
 Not recommended; increased risk of lactic acidosis
19
August 2013
www.aidsetc.org
ARVs during Pregnancy and Lactation (3)
 Special considerations in breast-feeding
 Counsel lactating HIV-exposed HCP to weigh risks
and benefits of continued breast-feeding both while
taking PEP and while being monitored for HIV
seroconversion
 Breast-feeding is not a contraindication to PEP,
especially given high risk of HIV transmission through
breast milk should acute HIV infection occur
 3-drug ARV regimens given to HIV-infected breastfeeding women has been shown to decrease risk of
transmission to their infants
 Consider stopping breast-feeding to eliminate risk of
HIV transmission
20
August 2013
www.aidsetc.org
Management of Occupational Exposure by
Emergency Physicians
 Institutions are recommended to develop clear
protocols for management of occupational
exposures, indicating:
 Formal expert consultation mechanism (eg, in-house ID
consultant or PEPline)
 Appropriate initial source patient and exposed HCP
laboratory testing
 Procedures for counseling exposed HCP
 Identifying and having an initial HIV PEP regimen
available
 Mechanism for outpatient HCP follow-up
21
August 2013
www.aidsetc.org
Management of HCP Potentially Exposed
to HIV
 Recommendations reflect expert opinion; limited
data on safety, tolerability, efficacy, and toxicity
of PEP
 Consider potential benefits and risks of PEP
(including possible toxicity and drug interactions)
 Consult with experts
 Reevaluate exposed HCP within 72 hours after
exposure, especially as additional information
about the exposure or source person becomes
available
22
August 2013
www.aidsetc.org
Source Patient HIV Testing
 If possible, determine the HIV status of
exposure source patient to guide appropriate
use of PEP
 For sources whose HIV status is unknown, rapid HIV
testing facilitates decisions about need to initiate or
continue PEP
 Investigation of whether a source patient might be in
the window period before HIV seroconversion is not
necessary, unless acute retroviral syndrome is
suspected
 4th-generation HIV Ag/Ab tests allow identification of
most HIV infections during the window period
23
August 2013
www.aidsetc.org
Source Patient HIV Testing (2)
 PEP initiation should not be delayed while
waiting for HIV test results
 If the source is found to be HIV negative, PEP
should be discontinued, and no follow-up HIV
testing for HCP is needed
24
August 2013
www.aidsetc.org
Timing and Duration of PEP
 PEP is most effective when begun soon after
the exposure, less effective as time increases
(animal studies)
 PEP should be started as soon as possible after
the exposure, preferably within hours
 Point at which no benefit may be gained is not
defined; in animal studies less effective if started
>72 hours after exposure
 Optimal duration unknown; 4 weeks appeared
protective in occupational and animal studies
 PEP should be taken for 4 weeks, if tolerated
25
August 2013
www.aidsetc.org
Selection of HIV PEP Drugs
 Stratifying severity of exposure to determine the
number of PEP drugs to be given is no longer
recommended
 PEP regimen of 3 (or more) ARVs is
recommended for all occupational HIV exposures
 Typically, 2-NRTI backbone + integrase
inhibitor, ritonavir-boosted protease inhibitor, or
NNRTI
 Other ARV classes may be indicated (eg, if
resistant virus), but consult with experts
26
August 2013
www.aidsetc.org
Selection of HIV PEP Drugs (2)
 No definitive data show increased efficacy of 3drug vs 2-drug PEP regimens; current
recommendation based on:
 Superior efficacy of 3 ARVs in reducing HIV
RNA in HIV-infected persons
 Concerns about source patient drug resistance
to ARVs
 Safety and tolerability of newer ARVs
 Potential for improved PEP adherence with
newer ARVs
27
August 2013
www.aidsetc.org
Selection of HIV PEP Drugs (3)
 Choose ARVs with favorable side effect profile
and convenient dosing schedule, to facilitate
adherence and completion of 4 weeks of PEP
 PEP not justified for exposures that pose
negligible risk of HIV transmission
 Reevaluate and modify PEP regimen whenever
additional information about the source is
obtained (eg, treatment history or ARV
resistance)
 Consultation with experts is recommended, but
should not delay PEP initiation
28
August 2013
www.aidsetc.org
PEP Regimens
 Preferred HIV PEP regimen:
 Raltegravir 400 mg BID + TDF/FTC (Truvada)
1 QD
29
August 2013
www.aidsetc.org
PEP Regimens (2)
 Alternative regimens (combine 1 drug or drug pair
from left column with 1 NRTI pair from right column):
•
•
•
•
•
•
Raltegravir
Darunavir + ritonavir
Etravirine
+
Rilpivirine
Atazanavir + ritonavir
Lopinavir/ritonavir
•
•
•
•
Tenofovir + emtricitabine
Tenofovir + lamivudine
Zidovudine + lamivudine
Zidovudine + emtricitabine
• Elvitegravir/cobicistat/tenofovir/emtricitabine
(Stribild)
30
August 2013
www.aidsetc.org
PEP Regimens (3)
 Alternative ARV agents for use as PEP
(only with expert consultation):







Abacavir¹
Efavirenz²
Enfuvirtide
Fosamprenavir
Maraviroc
Saquinavir
Stavudine
1
Use only with expert consultation, and in persons tested negative for
HLA B5701
2
31
Avoid during first trimester of pregnancy
August 2013
www.aidsetc.org
PEP Regimens (4)
 ARV agents generally not recommended
for PEP:
 Didanosine
 Nelfinavir
 Tipranavir
 ARV agents contraindicated as PEP:
 Nevirapine
32
August 2013
www.aidsetc.org
Selection of Drugs for PEP:
Consultation Is Part of the Guidelines
“Regular consultation with experts in
antiretroviral therapy and HIV
transmission is strongly recommended.”
33
August 2013
www.aidsetc.org
Resources for Consultation
 Local experts (eg, HIV or ID consultant,
hospital epidemiologist)
 National HIV/AIDS Clinicians’ Postexposure
Prophylaxis Hotline (PEPline)
 24-hour telephone consultation
service: 888-448-4911
34
August 2013
www.aidsetc.org
Situations in Which Expert Consultation
Is Advised
 Delayed exposure report (ie, >72 hours)
 Interval after which benefit from PEP undefined
 Unknown source (eg, needle in sharps disposal
container or laundry)
 Use of PEP to be decided on case-by-case basis
 Consider severity of exposure and epidemiologic likelihood of
HIV exposure
 Do not test needles or other sharp instruments for HIV
 Known or suspected pregnancy in the exposed
person
 Provision of PEP should not be delayed while
awaiting consultation
35
August 2013
www.aidsetc.org
Situations in Which Expert Consultation
Is Advised (2)
 Breast-feeding in the exposed person
 Provision of PEP should not be delayed while
awaiting consultation
 Known or suspected resistance of the source
virus to ARVs
 If source person’s virus is known or suspected to be
resistant to ≥1 of the drugs considered for PEP,
selection of drugs to which the source person’s virus
is unlikely to be resistant is recommended
 Initiation of PEP should not be delayed while
awaiting any results of resistance testing
36
August 2013
www.aidsetc.org
Situations in Which Expert Consultation
Is Advised (3)
 Toxicity of the initial PEP regimen
 Symptoms (eg, GI symptoms) often manageable
without changing PEP regimen by prescribing
antiemetic or antimotility agents
 Counseling and support for management of side
effects is very important
 Serious medical illness in the exposed person
 Significant illness (eg, renal disease) or
coadministration of multiple medications may
increase risk of drug toxicity and drug-drug
interactions
37
August 2013
www.aidsetc.org
Follow-Up of Exposed HCP
All exposed HCP should receive the following,
regardless of whether they receive PEP:
 Counseling
 Early reevaluation after exposure
 Follow-up testing and appointments
38
August 2013
www.aidsetc.org
Follow-Up of Exposed HCP (2)
 Postexposure counseling
 Exposed HCP should be advised to use precautions
(eg, use latex barriers during sex; avoid blood or tissue
donations, pregnancy, and, if possible, breast-feeding)
to prevent secondary transmission, especially during
the first 6-12 weeks postexposure
 For PEP recipients, provide information on:
 Need for adherence to PEP, importance of completing
PEP regimen
 Possible drug toxicities
 Possible drug interactions
 Symptoms to report to health care provider
39
August 2013
www.aidsetc.org
Follow-Up of Exposed HCP (3)
 Postexposure counseling (cont’d)
 Psychological impact of occupational
exposure to HIV may be substantial;
psychological counseling should be an
essential component of the management
and care of exposed HCP
40
August 2013
www.aidsetc.org
Follow-Up of Exposed HCP (4)
 Early reevaluation after exposure
 Reevaluate exposed HCP within 72 hours after
exposure, regardless of whether on PEP
 Gives additional opportunity for evaluation,
counseling, to reinforced adherence, identify
and manage early side effects, improve
likelihood of follow-up serologic testing, etc.
41
August 2013
www.aidsetc.org
Follow-Up of Exposed HCP (5)
 Follow-up testing
 HIV testing at baseline, 6 weeks, 12 weeks, and 6
months after exposure
 If 4th-generation p24 Ag/HIV Ab test is used: HIV
testing at baseline, 6 weeks, 12 weeks, and 4
months after exposure
 HIV testing for any exposed HCP with symptoms
compatible with acute retroviral syndrome,
regardless of interval since exposure
 If HIV infection is identified, refer for HIV care
 Report case to state health department and to
CDC COPHI coordinator (404-639-2050)
42
August 2013
www.aidsetc.org
Follow-Up of Exposed HCP (6)
Monitoring and management of PEP toxicity:
 Evaluation and laboratory testing at baseline and 2
weeks after starting PEP; additionally if symptoms
develop
 Laboratory tests: CBC, renal and hepatic function tests
 Other tests depending on specific toxicities of the drugs
in the PEP regimen and on the medical conditions of the
HCP
 Advise HCP of symptoms that require urgent evaluation
(eg, rash, fever, abdominal pain, icterus)
 If toxicity noted, consult with expert; consider
modification of PEP regimen
43
August 2013
www.aidsetc.org
Other Occupational and
Nonoccupational Exposures
 Managing exposure to hepatitis B and C
(see previous guideline: CDC. MMWR
2001;50(RR-11); online at
http://www.cdc.gov/mmwr/PDF/rr/rr5011.pdf
 Nonoccupational HIV exposure
(see separate guideline: CDC. MMWR
2005;54(RR-9); online at
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5
409a1.htm
44
August 2013
www.aidsetc.org
About This Slide Set
 This presentation was prepared by Susa
Coffey, MD, for the AETC National
Resource Center in August 2013
 See the most current version of this
presentation on the AETC NRC website:
http://www.aidsetc.org, or on AIDSinfo:
http://aidsinfo.nih.gov
45
August 2013
www.aidsetc.org