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Chapter
11
Postexposure Prophylaxis
Renslow
Sherer, MD
Bruce D. Agins, MD, MPH
Caroline J. Teter, PA-C, MPH
Overview
TOP
What is
postexposure prophylaxis (PEP)?
Postexposure
prophylaxis (PEP) prevents or aborts transmission of HIV with rapid
initiation of short-term antiretroviral therapy (ART) following
occupational or nonoccupational exposure. PEP should be considered
in all health care personnel (HCP) and non-HCP exposed to blood
or potentially infectious body fluids via percutaneous, mucous membrane,
and nonintact skin exposures, injection drug use, intentional or
unintentional sexual exposures, and human bites. Hepatitis B infection
may be prevented following administration of immune globulin and
vaccination when indicated.
PEP policies
should be instituted in all health care settings. The essential
elements include:
- Written
protocols for documenting and managing exposures
- Assessment,
counseling, and intervention immediately after any exposure
- Rapid access
to medications and/or immunization, if indicated
What do
we know about the effectiveness of PEP for HIV?
Retrospective
case-control studies support the efficacy of PEP for occupational
exposure to HIV, and 4 factors are associated with increased transmission
rates: 1) deep injury, 2) visible blood on device, 3) needle placement
in artery or vein, and 4) late stage HIV disease in source (this
risk factor was identified prior to viral load testing, thus high
viral load is likely an independent risk factor). Evidence of the
effectiveness of nonoccupational PEP comes from small observational
human studies, extrapolation of data showing the interruption of
maternal-infant transmission, and animal studies showing some degree
of protection from genitally and intravenously acquired HIV. Even
with optimal implementation, the degree of protection afforded by
PEP is incomplete. Studies of PEP have demonstrated the greatest
reduction in HIV transmission when antiretroviral medications are
administered immediately after exposure to HIV-infected blood and
body fluids. The efficacy of PEP is diminished after 36 hours and
is minimal after 72 hours.
What do
we know about the effectiveness of PEP for hepatitis B and C?
Hepatitis B
transmission can be prevented through administration of immune globulin
and hepatitis B vaccine. PEP for hepatitis C virus (HCV) has thus
far proven to be ineffective.
What body
fluids are infectious for HIV, HBV, HCV?
Blood is the
most infectious body fluid. In the health care setting, cerebrospinal,
synovial, pleural, peritoneal, pericardial, and amniotic fluids
are all considered potentially infectious, although the only documented
cases of occupational HIV infection have been with blood, body fluids
with visible blood, or HIV viral cultures. Unless there is visible
blood with the exposure, saliva, nasal discharge, tears, sweat,
vomit, urine, and feces are not infectious. Semen and vaginal secretions
are infectious for HIV, HBV, and HCV in the setting of nonoccupational
exposure.
Interventions
for PEP in Health Care Settings
TOP
What types
of exposures merit consideration of PEP in health care personnel
(HCP)?
HCP are at
increased risk from percutaneous, mucous membrane, and nonintact
skin exposures to bloodborne pathogens, including hepatitis B, hepatitis
C, and HIV. The risk of transmission is dependent on many factors,
including the type, amount, route, and severity of exposure, the
infection status of the source, and the HBV, HCV, and HIV immunity
of the exposed worker (see Tables 11-1 and 11-2).
Table
11-1. High-risk Occupational Exposures
Exposures
with higher risk of
transmission of bloodborne pathogens
- Deep
percutaneous injury
- Injury
with a hollow-bore blood-filled needle
- Exposure
to blood of a patient in an advanced disease stage (high
viral load)
- Exposure
to a large quantity of blood or body fluids
|
Table
11-2. Exposures with Low Risk of Transmission
of Bloodborne Pathogens
Exposures
with low risk of
transmission (PEP not recommended)
- Blood
or fluid splashes on intact skin
- Minor
scratches or abrasions without evidence of percutaneous
penetration
- Penetration
by small-bore needles without visible blood
|
An accurate
history of the exposure is essential in determining the real risk
of transmission. In studies, transmission of HIV by occupational
exposure has an estimated 0.3% risk with percutaneous exposure and
0.09% with mucous membrane splash (Bell, 1997). The risk of infection
for HBV (in individuals who have not been vaccinated to hepatitis
B, or who were vaccine unresponsive) after percutaneous exposure
is 37%-62% when the source is hepatitis B surface antigen (HbsAg)
positive and hepatitis B e antigen (HBeAg) positive, and the risk
of developing clinical hepatitis is 22%-31%. When the source is
HbsAg positive and hepatitis B e antigen negative, the risk of HBV
seroconversion is 1%-6%, and the risk of developing clinical hepatitis
is 23%-37%. The risk of transmission is higher, ie 22%-31%, when
the source has clinically evident hepatitis B hepatitis (Werner
and Grady, 1982; CDC, 2001). Transmission of HCV through occupational
exposure carries an average risk of 1.8%.
What are
immediate actions and initial considerations in PEP following a
possible occupational exposure?
First aid for
the HCP is the first immediate action, followed by collection of
information in order to assess the situation and make rapid decisions
regarding appropriate treatment (see Tables 11-3, 11-4, and 11-5).
Quick, expert action by the care provider is essential because the
effectiveness of PEP is variable and depends on the inoculum, type
of injury, potency of the PEP regimen, and speed with which treatment
is started. The decision to prescribe medications, as well as medication
administration, should be made within 4 hours of the exposure, and
must be made within 72 hours, and preferably sooner because of studies
suggesting that the efficacy of PEP is diminished after 36 hours.
Even with optimal implementation, ie within the first 4 hours, the
protection afforded by PEP is not 100%.
What counseling
and education should you give the HCP?
The exposed
HCP needs immediate counseling to assist in coping with the emotional
stress of the exposure, and may require follow up care by a mental
health professional. Psychological services should be available
24 hours a day, 7 days a week. A local crisis management team or
an employee assistance program (EAP) may be effective ways to address
this need.
The HCP should
be told the relative risk of infection with HIV, HBV, and HCV following
exposure, the effectiveness of PEP, and the risks and benefits of
PEP. Exposed persons should be advised to return immediately if
symptoms of acute HIV seroconversion occur, including fever, malaise,
rash, swollen lymph nodes, fatigue or myalgias (most likely to occur
2-6 weeks after exposure).
Providers should
advise exposed HCPs to prevent transmitting HIV to others, by means
of the following measures, until the HCP has a negative HIV test
6 months after exposure:
- Refrain
from donating blood, plasma, organs, tissue, or semen.
- Use barrier
protection during sexual activity.
- If HCP is
female, avoid pregnancy.
- If breast
feeding, consider discontinuing, to avoid the risk of HIV transmission
through breast milk.
If exposed
to HBV, the HCP should follow infection control procedures that
are in place at the institution.
Table
11-3: Algorithm for Actions after Occupational Exposure to Blood
or other Body Fluids Potentially Contaminated with Bloodborne
Pathogens
2.
Gather information about the exposure |
- Date
and time of exposure
- Details
of incident
- Where
and how exposure occurred
- If
related to a sharp device, type and brand
- Details
of exposure
- Type
and amount of fluid or material
|
3.
Obtain information about the exposure source |
-
Determine if possible whether source materials contained
HIV, HBV, or HCV (see Table 11-4).
- If
the source patient is HIV-positive, obtain a history of
the stage of disease, viral load, history of ART, and
information on ART resistance.
|
4.
Obtain information about the health care provider |
-
Determine HIV status (rapid test, if possible) and, HBV
vaccination and vaccine-response status (see
Table 11-5).
- Obtain
medical history, including pregnancy and breastfeeding.
|
5.
Assess the indication for PEP |
- Using
this information, assess the risk of exposure to HIV and
decide whether PEP is warranted in this situation.
- Assess
the risk of exposure to HBV.
|
6.
Manage the exposure |
- Ensure
appropriate and immediate access to informed counseling
for all exposed HCPs, even when PEP is not recommended.
- If
treatment for exposure to HIV is indicated, initiate medication
regimen as soon as possible, and definitely within 36
hours. Do not initiate treatment after 72 hours.
- If
treatment for exposure to hepatitis B is indicated, initiate
treatment as soon as possible within 24 hours of exposure;
the efficacy of HVIG after 7 days is unknown.
- Document
counseling, postexposure management, and followup.
|
Table
11-4. Evaluation of Occupational Exposure Sources
Known
Sources
|
Test
known sources for HbsAg, anti-HCV, and HIV antibodya, b:
- Direct
virus assays for routine screening of source patients
are not recommended.
- Use
a rapid HIV-antibody test if available.
- If
the source person is not infected with a bloodborne pathogen,
baseline testing or further followup of the exposed person
is not necessary.
|
For
sources whose infection status remains unknown (eg, the source
person refuses testing), consider medical diagnoses, clinical
symptoms, and history of risk behaviors. |
Do
not test discarded needles for bloodborne pathogens.
|
Unknown
Sources
|
For
unknown sources, evaluate the likelihood of exposure to a
source at high risk for infection. |
Consider
likelihood of bloodborne pathogen infection among patients
in the exposure setting. |
a With attention to State regulations regarding confidentiality and informed consent.
b If positive, confirmatory tests should be performed as appropriate including HBeAg, HIV Western blot, and HCV RNA.
Source: Centers for Disease Control and Prevention. "Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis." MMWR. 2001;50(RR11):20.
Table
11-5. Laboratory Evaluation and Followup of
Exposed Health Care Personnel
HIV
antibody test |
Test
HCP if source patient is HIV positive regardless of whether
PEP is given |
Baseline,
6 weeks, 12 weeks, 6 months (rapid test at baseline, if possible) |
HBV |
Test
if source patient is HBsAg or HBeAg positive |
Baseline
and 4-6 months ( or 1-2 months after last HBV vaccine) |
Anti
HCV |
Test
if source patient is HCV positive |
Baseline
and 4-6 months; HCV RNA at 4-6 weeks is optional |
Liver
enzymes |
Test
if source patient is HCV positive |
Baseline
and 4-6 months |
CBC,
renal function, and hepatic function |
If
PEP is warranted |
Prior
to initiating PEP and repeated in 2 weeks |
Are there
special considerations for PEP in dental settings?
Although the
number of exposures is relatively high in dental settings, the risk
of transmission is low and no different from other HCP settings.
Factors that are associated with increased risk of transmission
are failure to follow PEP protocols, failure to use puncture-proof
containers, treating >20 patients per day, failure to use eye
protection or masks, and male gender. For more information, see
Suggested Resources.
Interventions
for Nonoccupational PEP (NPEP)
TOP
What is
the role of nPEP for nonoccupational exposure?
PEP for nonoccupational
exposure to HIV (nPEP) is routinely being administered in cases
of sexual assault in hospital emergency departments and is increasingly
being made available during other cases of sexual exposure or injection
drug use exposure and in non-hospital settings. This issue is particularly
relevant in the care of HIV discordant couples. Research on risk
of HIV transmission from a single nonoccupational exposure is relatively
lacking compared with occupational exposures (see Table 11-6). A
national registry has been developed to gather the data with which
to develop a CDC recommendation for HIV PEP in the nonoccupational
setting. Information about this registry can be found at http://www.hivpepregistry.org.
In general, PEP for non-HCP is modeled after PEP interventions and
procedures for HCP.
Table
11-6. Estimated Risk of HIV Transmission
Following Different Types of Exposures
Needle-sharing
exposure with an infected source |
0.67%
|
Receptive
anal intercourse with an infected source |
0.5%-3.0%
|
Receptive
vaginal intercourse with an infected source |
0.1%
|
Insertive
anal intercourse with an infected source |
0.065%
|
Insertive
vaginal intercourse with an infected source |
0.05%
|
Oral
sex with ejaculation with an infected source |
Conflicting
data; however, risk is considered to be extremely low
(<0.05%) |
Source:
Mayer KH, Anderson DJ. "Heterosexual HIV transmission."
Infect Agents Dis. 1995;4:273-284.
What needs
to be evaluated for the possible administration of PEP in the nonoccupational
setting?
Factors to
be considered when considering PEP for nonoccupational exposure
are similar to those for occupational exposure, including 1) HIV
status of potentially exposed person (a rapid test can be done in
20 minutes), 2) timing (within 72 hours, with rare exception) and
frequency of exposure (recurrent exposure would require ongoing
PEP and suggests need for prevention counseling as the primary intervention),
3) HIV status of source (if unknown, PEP can be initiated while
this is being assessed and discontinued if HIV infection of the
source cannot be confirmed), 4) transmission risk of behavior (see
Table 11-6), 5) presence of other sexually transmitted diseases,
particularly genital ulcer disease (which can facilitate HIV transmission).
Exposures to persons who have recently seroconverted may carry a
higher risk of transmission because of high HIV viremia.
What is
the role of PEP for discordant couples?
Discordant
couples (couples in which one person is infected and the other is
not) should be routinely educated about how to protect the noninfected
person. Both partners should be made aware of the possible effectiveness
of PEP in cases of intended or unintended exposures and the importance
of early initiation of PEP if it is to be used. Repeated, frequent
exposures should signal providers to exercise caution about administration
of PEP, since PEP should not be a substitute for avoidance of high-risk
behavior. Any request for PEP should prompt additional counseling
and psychosocial support to enhance behaviors to prevent HIV infection.
What is
the role of PEP following sexual assault?
Persons who
have been sexually assaulted should be considered at risk for HIV
and HBV, as well as other STDs. The decision to begin PEP should
not be based on the perpetrator's likelihood of infectivity or delayed
pending the test results of the source (unless immediately available).
Pregnancy is an important consideration when considering PEP, and
emergency contraception should be considered for women who have
been sexually assaulted.
A survivor
of sexual assault may have had multiple exposures. When considering
PEP, the most recent exposure should be considered, and PEP should
be initiated if the exposure took place within 72 hours before the
patient arrived at the health care facility. As with any consideration
for PEP, weighing the benefits of PEP versus the possibility of
medication side effects, the importance of completing the 28-day
regimen and adherence issues should all be considered.
The provider
should be sensitive to the psychosocial needs of the person who
was sexually assaulted; the patient may not be physically or emotionally
able to weigh the pros and cons about beginning PEP. Therefore,
it is important to follow up within 24 hours to either emphasize
the importance of adherence or to continue the discussion about
initiating PEP if is to occur within the 72-hour window.
See Suggested
Resources for more information and resources in addressing issues
of sexual assault.
What if
the person who is exposed is a minor?
In cases involving
minors, parental or guardian participation is extremely important,
but parental or guardian consent for PEP may not be required. Nonetheless,
in all cases, parental or guardian participation should continue
to be sought in the emergency situation and during followup. State
laws and hospital policy must be considered.
HIV
PEP Treatment Recommendations
TOP
If PEP is
found to be appropriate, what information does the exposed person
need regarding treatment?
The exposed
person must understand the risks and benefits of HIV PEP, potential
medication toxicities and side effects, instructions on how and
when to take the medication, and the importance of adherence to
the regimen, including completing the course of 28 days. Women should
understand pregnancy-associated risks, including perinatal transmission
and teratogenicity. Breast-feeding should be discontinued until
the woman receives an HIV-negative result 6 months after exposure.
What are
HIV treatment recommendations and options for PEP?
Currently recommended
regimens are shown in Tables 11-7, 11-8, and 11-9; however, these
recommendations may be altered if the source patient has a history
of ART or known viral resistance, is pregnant, breast-feeding, has
hepatic or renal disease, or is taking certain medications. If viral
resistance in the source patient is known or suspected, an HIV expert
should be consulted prior to initiating HIV PEP medications.
Basic HIV PEP regimens include 2 NRTIs. These regimens are relatively
simple, ie 1 or 2 pills twice a day, well tolerated, and of sufficient
potency to meet the needs of PEP. However, they are substantially
less potent than 3-drug regimens. As noted below, some experts,
including the authors, believe that only 3-drug regimens should
be used for PEP, particularly in the current era of greatly simplified
and somewhat better tolerated 3-drug regimens.
Table
11-7. Recommended HIV Postexposure Prophylaxis for
Mucous Membrane Exposures and Nonintact Skin8
Exposures
Small
Volume¶ |
Consider
basic 2-drug PEP |
Recommend
basic 2-drug PEP |
Generally,
no PEP warranted; however, consider basic 2-drug PEP** for source
with HIV risk factors§ |
Generally,
no PEP warranted; however, consider basic 2-drug PEP** in settings
where exposure to HIV-infected persons is likely |
No
PEP warranted |
Large
Volume |
Recommend
basic 2-drug PEP |
Recommend
expanded 3-drug PEP |
Generally,
no PEP warranted; however, consider basic 2-drug PEP** for source
with HIV risk factors§ |
Generally,
no PEP warranted; however, consider basic 2-drug PEP** in settings
where exposure to HIV-infected persons is likely |
No
PEP warranted |
8
For skin exposures, follow-up is indicated only if there is evidence
of compromised skin integrity (e.g., dermatitis, abrasion, or
open wound).
* HIV-Positive,
Class 1 asymptomatic HIV infection or known low viral load (e.g.,
<1,500 RNA copies/mL). HIV-Positive, Class 2 - symptomatic
HIV infection, AIDS, acute seroconversion, or known high viral
load. If drug resistance is a concern, obtain expert consultation.
Initiation of postexposure prophylaxis (PEP) should not be delayed
pending expert consultation, and, because expert consultation
alone cannot substitute for face-to-face counseling, resources
should be available to provide immediate evaluation and follow-up
care for all exposures.
+ Source
of unknown HIV status (e.g., deceased source person with no samples
available for HIV testing).
Ø
Unknown source (e.g. splash from inappropriately disposed blood).
¶ Small volume (i.e., a few drops).
** The designation
, "consider PEP," indicates that PEP is optional and
should be based on an individualized decision between the exposed
person and the treating clinician.
§ If
PEP is offered and taken and the source is later determined to
be HIV-negative, PEP should be discontinued.
Large
volume (i.e., major blood splash).
Source: Centers
for Disease Control and Prevention. Updated U.S. Public Health
Service Guidelines for the Management of Occupational Exposures
to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis.
MMWR 2001;50(RR11):25.
Table
11-8. Recommended HIV Postexposure Prophylaxis
for Percutaneous Injuries
Exposure
Type |
HIV-Positive
Class 1* |
HIV
Positive Class 2* |
Source
of unknown HIV status+ |
Unknown
SourceØ |
HIV-Negative |
Infection
Status of Sources
|
Less
Severe¶ |
Recommend
basic 2-drug PEP |
Recommend
expanded 3-drug PEP |
Generally,
no PEP warranted; however, consider basic 2-drug PEP** for source
with HIV risk factors§ |
Generally,
no PEP warranted; however, consider basic 2-drug PEP** in settings
where exposure to HIV-infected persons is likely |
No
PEP warranted |
More
Severe |
Recommend
expanded 3-drug PEP |
Recommend
expanded 3-drug PEP |
Generally,
no PEP warranted; however, consider basic 2-drug PEP** for source
with HIV risk factors§ |
Generally,
no PEP warranted; however, consider basic 2-drug PEP** in settings
where exposure to HIV-infected persons is likely |
No
PEP warranted |
* HIV-Positive,
Class 1 asymptomatic HIV infection or known low viral load (e.g.,
<1,500 RNA copies/mL). HIV-Positive, Class 2 - symptomatic
HIV infection, AIDS, acute seroconversion, or known high viral
load. If drug resistance is a concern, obtain expert consultation.
Initiation of postexposure prophylaxis (PEP) should not be delayed
pending expert consultation, and, because expert consultation
alone cannot substitute for face-to-face counseling, resources
should be available to provide immediate evaluation and follow-up
care for all exposures.
+ Source
of unknown HIV status (e.g., deceased source person with no samples
available for HIV testing).
Ø
Unknown source (e.g. a needle from a sharps disposal container).
¶ Less severe (e.g., solid needle and superficial injury).
** The designation
, "consider PEP," indicates that PEP is optional and
should be based on an individualized decision between the exposed
person and the treating clinician.
§ If
PEP is offered and taken and the source is later determined to
be HIV-negative, PEP should be discontinued.
More
severe (e.g, large-bore hollow needle, deep puncture, visible
blood on device, or needle used in patient's artery or vein.
Source: Centers
for Disease Control and Prevention. Updated U.S. Public Health
Service Guidelines for the Management of Occupational Exposures
to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis.
MMWR 2001;50(RR11):24
Table
11-9. Treatment Options for 2- and 3-drug PEP
Basic
2-drug PEP |
zidovudine
(AZT) 300 mg bid + lamivudine (3TC) 150 mg bid (may be taken
as Combivir bid) |
stavudine
(d4T) 40 mg bid + 3TC 150 mg bid |
stavudine
(D4T) 40 mg bid + didanosine (ddI) 400 mg qd on an empty stomach (No longer recommended because of increased toxicity unless
a suitable alternative is not available.) |
3-drug
PEP |
One
of the above NRTI* combinations plus a third drug, usually a
PI**, an NTRTI#,or an NNRTI,*** to be determined in consultation
with an HIV expert. |
nevirapine
(NVP) (No longer recommended for PEP due to the potential for
severe liver toxicity.) |
*
NRTI: nucleoside or nucleoside reverse transcriptase inhibitor
** PI: protease inhibitor
# NTRTI: nucleotide reverse transcriptase inhibitor, i.e., tenofovir
(TDF)
*** NNRTI: non-nucleoside reverse transcriptase inhibitors, i.e.,
efavirenz (EFV)
Three-drug
regimens, comparable to highly active antiretroviral therapy (HAART)
regimens used to treat HIV infection, are recommended for more severe
exposures, which carry a higher risk of HIV transmission, or with
exposures to sources with known HIV resistance mutations. The 3-drug
regimens increase the risk of medication toxicity and may worsen
adherence, all of which should be weighed when choosing an HIV PEP
regimen. The majority of exposures in the past have resulted in
the administration of 2 medications; 3-drug regimens should be chosen
with the advice of an HIV expert. In accordance with the same principles
that are used in treating HIV-positive persons; some experts believe
that 3-drug PEP regimens should be the mainstay of PEP and that
2-drug regimens should be used only during extenuating circumstances
such as an inability to tolerate a protease inhibitor (PI). For
example, the New York State PEP Guidelines now recommend zidovudine
and lamivudine (Combivir) plus tenofovir (two pills in the morning
and one pill in the evening) as the standard PEP intervention. (http:\\www.hivguidelines.org)
Although the
current data on PEP for nonoccupational HIV exposures are scant,
treatment recommendations for occupational PEP can be generalized
to nonoccupationally exposed persons. As in the case of PEP in HCP,
nonjudgmental counseling directed towards the reduction of future
exposures is an important part of PEP in nonHCP.
What are
the side effects of HIV PEP?
Side effects
of HIV PEP regimens are common and occur in 30%-50% of patients.
Severe side effects occur in 5%-30% of patients and often require
discontinuation. Common side effects include gastrointestinal symptoms
such as nausea, vomiting, diarrhea, and abdominal pain; rash; fatigue;
headache and dizziness; cytopenia; neuropathy; hepatitis; and many
others. In reported series to date, over half of HCP in PEP programs
fail to complete their 28-day regimens because of side effects.
Regularly scheduled followup either in person or by phone has been
shown to greatly improve adherence. Refer to other chapters for
more detail on symptom management and metabolic complications with
ART.
What medication
toxicities should be monitored?
Regular laboratory
evaluation for medication toxicity and seroconversion should be
performed (see Table 11-5). A complete blood count and renal and
hepatic function tests should be done before initiating PEP and
repeated in 2 weeks. Continued monitoring is recommended for abnormal
lab test results, and medication changes should be considered if
abnormalities are severe. Specific monitoring parameters vary with
the regimen; for example, glucose levels should be monitored if
a PI is used. If the PI is indinavir (IDV) a urinalysis should also
be checked to monitor for crystalluria and hematuria. Tenofovir
(TDF) is well tolerated, but should be used with caution and careful
monitoring in patients with compromised renal function (Refer to
Drug Information Tables in the Pocket Guide for medication side
effects.)
Two regimens deserve special consideration. Hepatotoxicity, Stevens-Johnson
syndrome, and fatal hepatic necrosis have occurred in HCP treated
with nevirapine (NVP) as part of their PEP regimen, and therefore
its use is not recommended, given the variety of other options.
Pregnant women treated with stavudine (d4T) and didanosine (ddI)
were found to be at increased risk for fatal and non-fatal lactic
acidosis, and therefore this combination is not recommended in the
treatment of pregnant women. In addition, recent clinical trial
data showed a higher rate of adverse effects with the combination
of stavudine and didanosine in adults, and their use in combination
is not recommended unless other alternatives are not available.
What are
the treatment recommendations when the source patient is known to
have specific HIV resistance mutations?
Resistance
to HIV medications is an important consideration in the treatment
of HIV-positive persons, and known resistance in the source patient
should be a consideration when choosing an appropriate HIV PEP regimen.
In addition, because of reported increases in resistance mutations
in recently acquired HIV infection in several cities in the United
States, resistance is increasingly a concern in untreated patients,
and thus for PEP in exposures to unknown sources. HIV PEP failures
attributed to exposure to resistant virus have been reported in
the literature.
Unfortunately,
resistance test results are often unavailable at the time of the
consideration of PEP, and PEP should not be unduly delayed while
this information is sought. A thorough drug, adherence, and HIV
history from the source patient and consultation with an HIV expert
is needed to make the optimal treatment recommendation.
When should
expert consultation be sought?
Expert consultation
is potentially valuable in many circumstances with PEP. As above,
expert consultation is indicated in the setting of known or suspected
drug resistance in the source in order to select drugs to which
the patient's virus is likely to be susceptible. Other situations
include:
- Delayed
report of exposure, since the interval after which there is no
benefit from PEP is undefined, in order to determine if PEP is
still indicated
- Unknown
status of the source, since the decision regarding the use of
PEP should be individualized, based on the estimated likelihood
of risk to the HCP, considering the severity of the exposure and
the epidemiologic likelihood of HIV exposure
- Known or
suspected pregnancy in the exposed person, in which case specific
treatment recommendations may require modification
- Possible
toxicity of the initial PEP regimen, in which case modification
of the regimen and/or treatment of the adverse side effect may
be considered
Hepatitis
PEP Treatment Recommendations
TOP
What are
the treatment recommendations and options for possible hepatitis
B exposure?
HBIG and immunization
against HBV following exposure are the most effective methods to
prevent HBV transmission (see Table 11-10). PEP for HBV with multiple
doses of HBIG has been shown to be 75%-95% effective. Pregnant women
can safely receive both the HBV vaccination and HBIG. When considering
PEP for HBV exposures, both the source patient's HbsAg status and
the exposed person's vaccination status and antibody response should
be considered. Both HBIG and the hepatitis B vaccine should be administered
within 24 hours of exposure. Anti-HBs should be drawn 1-2 months
after completion of the third vaccine, but it is unreliable if the
exposed person has received HBIG within the past 3-4 months.
Table 11-10.
Recommended Postexposure Prophylaxis
for Exposure to Hepatitis B Virus
HBIG§
x 1 and initiate HR vaccine series¶ |
|
|
No
treatment |
No
treatment |
No
treatment |
HBIG
x 1 and initiate revaccination or HVIG x 2 |
No
treatment |
If
know high risk source, treat as if sources were HBsAg positive |
Test
exposed person for anti-HBs¶¶
1. If adequate,** no treatment is necessary
2. If inadequateØ, administer HBIG x 1 and vaccine booster
|
No
treatment |
Test
exposed person for anti-HBs
1. If
adequate¶, no treatment is necessary
2. If
inadequate¶, administer vaccine booster and recheck titer
in 1-2 months
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* Persons who
have previously been infected with HBV are immune to reinfection
and do not require postexposure prophylaxis.
+ Hepatitis
B surface antigen.
§ Hepatitis
B immune globulin; dose is 0.06 mL/kg intramuscularly.
¶ Hepatitis B
vaccine.
** A responder
is a person with adequate levels of serum antibody to HBsAg (ie,
anti-HBs = 10mlU/mL).
Ø A
nonresponder is a person with inadequate response to vaccination
(ie, serum anti-HBs < 10mlU/mL).
The
option of giving one dose of HBIG and reinitiating the vaccine series
is preferred for nonresponders who have not completed a second 3-dose
vaccine series. For persons who have previously completed a second
vaccine series but failed to respond, two doses of HBIG are preferred.
¶¶ Antibody
to HBsAg.
Source: Centers
for Disease Control and Prevention. Updated U.S. Public Health Service
Guidelines for the Management of Occupational Exposures to HBV,
HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR
2001;50(RR11):22.
What are
the treatment recommendations and options for possible hepatitis
C exposure?
There are no
recommended prophylactic treatments after exposure to HCV blood
or body fluids. Current data do not support treatment during acute
HCV infection at this time; referral of an individual with recently
acquired HCV to a specialist in HCV care is appropriate.
Following exposure,
testing should be performed on the source for anti-HCV. If positive,
the exposed person should be tested for anti-HCV and alanine aminotransferase
(ALT) initially and in 4-6 months. HCV-RNA and ALT at 4-6 weeks
are optional. All anti-HCV results should be confirmed by recombinant
immunoblot assay; if positive an HCV RNA should be drawn. Drawing
an HCV RNA at 4-6 weeks may be done for earlier diagnosis, but the
person should be counseled that false-positives do occur. Current
research supports early diagnosis of HCV as basis for the most effective
management after exposure are known. Exposed persons should be counseled
to refrain from donating blood, plasma, organs, tissue, or semen.
Although the transmission risk by sexual activity is low, it is
reasonable to recommend a barrier method until the results of testing
6 months after exposure are known. There are currently no recommendations
to make any changes in breast-feeding, pregnancy, or professional
activities. Mental health counseling should be offered as needed.
- The goals
of PEP are to prevent or abort the transmission of HIV and hepatitis
B virus (HBV) and to enable early diagnosis of hepatitis C virus
(HCV).
- All exposed
persons need followup within 24-48 hours depending on the pathogen.
- HIV PEP,
if determined to be appropriate, should be provided preferably
immediately, and definitely within 36 hours of exposure. PEP is
NOT recommended for minor exposures. If the provider is inexperienced
in using HIV medications or managing PEP patients, an HIV specialist
should be consulted before initiating treatment.
- The risk
of transmission of HBV is far greater than of HIV or HCV. All
HCPs should be vaccinated against HBV. HBIG is highly effective
in preventing transmission of HBV.
- There is
currently no recommended PEP medication for HCV. If possible,
the source should be tested for antiHCV, and if positive, the
exposed person should be monitored.
- PEP should
be available in all health care settings. PEP protocols should
be developed, regularly updated, and included in regular employee
training programs.
- PEP for
nonoccupational exposure (nPEP) is modeled after PEP for occupational
exposures. nPEP is routinely administered in cases of sexual assault
in emergency departments, and is increasingly being made available
for other cases of sexual exposure or injection drug use exposure
in non-hospital settings.
References
TOP
Bell DM. "Occupational
risk of human immunodeficiency virus infection in healthcare workers:
an overview." Am J Med. 1997;102(suppl 5B):9-15.
Cardo DM, Culver
DH, Ciesielski CA, et al. "A case-control study of HIV seroconversion
in health care workers after percutaneous exposure." N Engl
J Med. 1997;337:1485-1490.
Centers for
Disease Control and Prevention. "Updated guidelines for the
management of occupational exposures to HBV, HCV, and HIV and recommendations
for postexposure prophylaxis." Public Health Service. MMWR.
2001:50(RR11):1-42.
Centers for
Disease Control and Prevention. "Management of possible sexual,
injecting-drug-use, or other nonoccupational exposure to HIV, including
considerations related to antiretroviral therapy." Public Health
Service Statement. MMWR. 1998; 47(RR-17):1-14.
Centers for
Disease Control and Prevention. "Recommendations for the prevention
and control of hepatitis C virus (HCV) infection and HCV-related
chronic disease." MMWR. 1998; 47(RR-19):1-39.
Gerberding
JL. "Occupational exposure to HIV in health care settings."
N Engl J Med. 2003;348:826-833.
New
York State Department of Health AIDS Institute. HIV PEP Guidelines.
Accessed 1/04.
Mayer KH, Anderson
DJ. "Heterosexual HIV transmission." Infect Agents
Dis. 1995;4:273-284.
Stephenson
J. "PEP talk: treating nonoccupational HIV exposure".
JAMA. 2003;289:287-288.
Werner BG,
Grady GF. "Accidental hepatitis-B-surface-antigen-positive
inoculations: use of e antigen to estimate infectivity."
Ann Intern Med. 1982;97:367-369.
Cases
TOP
1.
An employee states that she has just punctured herself
with a needle after drawing a patient's blood. The patient has already
left the clinic and no one knows anything about his medical history.
The employee completed the HBV vaccination series and is hepatitis
B surface antibody (HBsAb) positive. During the investigation the
HIV prevalence in this setting was found to be low.
Question:
What is the risk of HIV transmission?
Answer:
The risk of HIV transmission after a puncture wound with a hollow-bore
needle is 0.3%. It is important to remember that the risk of infection
is higher when there is a large-volume exposure, a deep percutaneous
injury, or an injury with a hollow-bore, blood-filled needle, or
if the source has advanced HIV disease or has a high level of HIV
viremia. The current CDC recommendations advise against HIV PEP
when the source is unknown and in settings where the HIV prevalence
is low.
Question:
What counseling and followup should be recommended?
Answer:
Because of the low prevalence of HIV in this setting, the employee
should be advised against taking HIV medications. Also, because
she is HBsAb positive she is not a candidate for HBV PEP. The HCP
should be advised to refrain from donating blood, plasma, organs,
or tissue, to use barrier methods during sexual activities, and
to refrain from sharing any injection or other drug use equipment.
She should also be counseled about universal precautions and administration
should take steps to reduce the risk of future accidental needle
sticks. She should be educated about the symptoms of acute HIV and
advised to return immediately if those symptoms occur. Mental health
counseling should also be offered.
A baseline
HIV antibody and anti-HCV should be drawn. HIV antibody should be
repeated at 6 weeks, 3 months and 6 months after exposure. A 12-month
followup is recommended if the source is found to be coinfected
with HIV and HCV, or if the exposed becomes infected with HCV following
exposure. Anti-HCV and ALT should be repeated within 4-6 months
and if positive should be confirmed with supplemental tests.
2.
A patient known to be HIV negative 6 months ago comes
to the clinic stating that last night he was the receptive partner
of unprotected sexual intercourse with his HIV-positive partner
when the condom broke. His partner has been HIV-positive for 5 years,
currently has an undetectable viral load, and is taking Combivir
(zidovudine + lamivudine) and efavirenz (EFV). He has never had
a resistance test.
Question:
Should the patient take HIV PEP medications?
Answer:
Although the current recommendations for nonoccupational exposures
were released in 1998 and at that time found that PEP for nonoccupational
HIV exposure was still unproven, current data support treating.
Receptive anal intercourse with an HIV-positive partner carries
with it a risk of transmission of 0.5%-3.0%. Your patient's risk
is likely lower because of his partner's low level of viremia. PEP
in nonoccupational settings is modeled after PEP for HCPs. In this
case, the patient had a large exposure from a known HIV-positive
source with an undetectable viral load.
Following the
model for PEP for HCPs, the patient should be treated ASAP, ie within
4 to 72 hours but not more than 72 hours after exposure and receive
2 medications, although some experts would recommend using 3 medications.
It would be reasonable to place the patient on the same combination
as his partner because his partner has exhibited good adherence
and good virologic control. Treatment should continue for 28 days.
The patient
should be counseled about medication side effects and the importance
of adherence and followup. Common side effects should be anticipated
and pre-empted with counseling and, in some cases, treatment. Changing
medications and/or modifying the dosage regimen may increase the
likelihood of completion of the HIV PEP regimen. And finally, the
patient should be educated about the symptoms of acute HIV infection
and advised to return immediately if those symptoms occur.
Question:
What lab specimens should be drawn?
Answer:
A baseline HIV Ab should be drawn and repeated at 6 weeks, 3 months,
6 months and 12 months after exposure, as well as an HBsAg, HBsAb,
and HCV Ab. If he were unvaccinated against HAV or HBV then vaccination
should be initiated immediately. Laboratory monitoring for drug
toxicity should be performed at baseline and then 2 weeks after
initiating therapy. The medical record of the patient's partner
should immediately be reviewed, and treatment for HBV, HCV, or other
sexually transmitted diseases should occur, if any of these are
found. Expert consultation should be sought if needed.
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