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Updated U.S. Public Health Service Guidelines for the Management
of Occupational Exposures to HIV and Recommendations for Postexposure
Prophylaxis
Prepared by
Adelisa L. Panlilio, MD1
Denise M. Cardo, MD1
Lisa A. Grohskopf, MD2
Walid Heneine, PhD2
Clara Sue Ross, MD3
1Division of Healthcare Quality Promotion, National Center
for Infectious Diseases
2Division of HIV/AIDS Prevention, National Center for HIV, STD,
and TB Prevention
3Division of Surveillance, Hazard Evaluations, and Field Studies,
National Institute for Occupational Safety and Health
The
material in this report originated in the National Center for Infectious
Diseases, Anne Schuchat, MD, Acting Director; Division of Healthcare
Quality Promotion, Denise M. Cardo, MD, Director.
MMWR September 30, 2005 / 54(RR09);1-17.
Recommendations
for the Management of HCP Potentially Exposed to HIVCorresponding
preparer:
Adelisa L. Panlilio, MD, MPH, Division of Healthcare Quality Promotion,
National Center for Infectious Diseases, CDC, 1600 Clifton Rd.,
NE, MS E-68, Atlanta, GA 30333. Telephone: 404-498-1265; Fax: 404-498-1244;
E-mail: alp4@cdc.gov.
Summary
Introduction
Recommendations
for the Management of HCP Potentially Exposed to HIV
This
report updates U.S. Public Health Service recommendations for the
management of health-care personnel (HCP) who have occupational
exposure to blood and other body fluids that might contain human
immunodeficiency virus (HIV). Although the principles of exposure
management remain unchanged, recommended HIV postexposure prophylaxis
(PEP) regimens have been changed. This report emphasizes adherence
to HIV PEP when it is indicated for an exposure, expert consultation
in management of exposures, follow-up of exposed workers to improve
adherence to PEP, and monitoring for adverse events, including seroconversion.
To ensure timely postexposure management and administration of HIV
PEP, clinicians should consider occupational exposures as urgent
medical concerns.
Although
preventing exposures to blood and body fluids is the primary means
of preventing occupationally acquired human immunodeficiency virus
(HIV) infection, appropriate postexposure management is an important
element of workplace safety. In 1996, the first U.S. Public Health
Service (PHS) recommendations for the use of postexposure
prophylaxis (PEP) after occupational exposure to
HIV were published; these recommendations have been updated twice
(1--3). Since publication of the most recent guidelines in
2001, new antiretroviral agents have been approved by the Food and
Drug Administration (FDA), and additional information has become
available regarding the use and safety of HIV PEP. In August 2003,
CDC convened a meeting of a PHS interagency working group* and consultants
to assess use of HIV PEP. On the basis of this discussion, the PHS
working group decided that updated recommendations for the management
of occupational exposure to HIV were warranted.
This
report modifies and expands the list of antiretroviral medications
that can be considered for use as PEP. This report also emphasizes
prompt management of occupational exposures, selection of tolerable
regimens, attention to potential drug interactions involving drugs
that could be included in HIV PEP regimens and other medications,
consultation with experts for postexposure management strategies
(especially determining whether an exposure has actually occurred)
and selection of HIV PEP regimens, use of HIV rapid testing, and
counseling and follow-up of exposed personnel.
Recommendations
on the management of occupational exposures to hepatitis B virus
or hepatitis C virus have been published previously (3) and
are not included in this report. Recommendations for nonoccupational
(e.g., sexual, pediatric, and perinatal) HIV exposures also have
been published previously (4--6).
Definition
of Health-Care Personnel and Exposure
The
definitions of health-care personnel (HCP) and occupational exposures
are unchanged from those used in 2001 (3). The term HCP refers
to all paid and unpaid persons working in health-care settings who
have the potential for exposure to infectious materials (e.g., blood,
tissue, and specific body fluids and medical supplies, equipment,
or environmental surfaces contaminated with these substances). HCP
might include, but are not limited to, emergency medical service
personnel, dental personnel, laboratory personnel, autopsy personnel,
nurses, nursing assistants, physicians, technicians, therapists,
pharmacists, students and trainees, contractual staff not employed
by the health-care facility, and persons not directly involved in
patient care but potentially exposed to blood and body fluids (e.g.,
clerical, dietary, housekeeping, maintenance, and volunteer personnel).
The same principles of exposure management could be applied to other
workers who have potential for occupational exposure to blood and
body fluids in other settings.
An
exposure that might place HCP at risk for HIV infection is defined
as a percutaneous injury (e.g., a needlestick or cut with a sharp
object) or contact of mucous membrane or nonintact skin (e.g., exposed
skin that is chapped, abraded, or afflicted with dermatitis) with
blood, tissue, or other body fluids that are potentially infectious.
In addition to blood and visibly bloody body fluids, semen and vaginal
secretions also are considered potentially infectious. Although
semen and vaginal secretions have been implicated in the sexual
transmission of HIV, they have not been implicated in occupational
transmission from patients to HCP. The following fluids also are
considered potentially infectious: cerebrospinal fluid, synovial
fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic
fluid. The risk for transmission of HIV infection from these fluids
is unknown; the potential risk to HCP from occupational exposures
has not been assessed by epidemiologic studies in health-care settings.
Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and
vomitus are not considered potentially infectious unless they are
visibly bloody; the risk for transmission of HIV infection from
these fluids and materials is low (7).
Any
direct contact (i.e., contact without barrier protection) to concentrated
virus in a research laboratory or production facility requires clinical
evaluation. 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. Transmission of HIV
infection by this route has been reported rarely, but not after
an occupational exposure (8--12).
Risk
for Occupational Transmission of HIV
The
risks for occupational transmission of HIV have been described;
risks vary with the type and severity of exposure (2,3,7).
In prospective studies of HCP, the average risk for HIV transmission
after a percutaneous exposure to HIV-infected blood has been estimated
to be approximately 0.3% (95% confidence interval [CI] = 0.2%--0.5%)
(7) and after a mucous membrane exposure, approximately 0.09%
(CI = 0.006%--0.5%) (3). Although episodes of HIV transmission
after nonintact skin exposure have been documented, the average
risk for transmission by this route has not been precisely quantified
but is estimated to be less than the risk for mucous membrane exposures.
The risk for transmission after exposure to fluids or tissues other
than HIV-infected blood also has not been quantified but is probably
considerably lower than for blood exposures.
Epidemiologic
and laboratory studies suggest that multiple factors might affect
the risk for HIV transmission after an occupational exposure (3).
In a retrospective case-control study of HCP who had percutaneous
exposure to HIV, increased risk for HIV infection was associated
with exposure to a larger quantity of blood from the source person
as indicated by 1) a device (e.g., a needle) visibly contaminated
with the patient's blood, 2) a procedure that involved a needle
being placed directly in a vein or artery, or 3) a deep injury.
The risk also was increased for exposure to blood from source persons
with terminal illness, possibly reflecting either the higher titer
of HIV in blood late in the course of acquired immunodeficiency
syndrome (AIDS) or other factors (e.g., the presence of syncytia-inducing
strains of HIV). A laboratory study that demonstrated that more
blood is transferred by deeper injuries and hollow-bore needles
lends further support for the observed variation in risk related
to blood quantity (3).
The
use of source-person viral load as a surrogate measure of viral
titer for assessing transmission risk has not yet been established.
Plasma viral load (e.g., HIV RNA) reflects only the level of cell-free
virus in the peripheral blood; latently infected cells might transmit
infection in the absence of viremia. Although a lower viral load
(e.g., <1,500 RNA copies/mL) or one that is below the limits
of detection probably indicates a lower titer exposure, it does
not rule out the possibility of transmission.
Antiretroviral
Agents for PEP
Antiretroviral
agents from five classes of drugs are currently available to treat
HIV infection (13,14). These include the nucleoside reverse
transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase
inhibitors (NtRTIs), nonnucleoside reverse transcriptase inhibitors
(NNRTIs), protease inhibitors (PIs), and a single fusion inhibitor.
Only antiretroviral agents approved by FDA for treatment of HIV
infection are included in these guidelines. The recommendations
in this report provide guidance for two- or-more drug PEP regimens
on the basis of the level of risk for HIV transmission represented
by the exposure (Tables
1 and 2;
Appendix).
Toxicity
and Drug Interactions of Antiretroviral Agents
Persons
receiving PEP should complete a full 4-week regimen (3).
However, as a result of toxicity and side effects among HCP, a substantial
proportion of HCP have been unable to complete a full 4-week course
of HIV PEP (15--20). Because all antiretroviral agents have
been associated with side effects (Table
3), the toxicity profile of these agents, including the frequency,
severity, duration, and reversibility of side effects, is an important
consideration in selection of an HIV PEP regimen. The majority of
data concerning adverse events have been reported primarily for
persons with established HIV infection receiving prolonged antiretroviral
therapy and therefore might not reflect the experience of uninfected
persons who take PEP. Anecdotal evidence from clinicians knowledgeable
about HIV treatment indicates that antiretroviral agents are tolerated
more poorly among HCP taking HIV PEP than among HIV-infected patients
on antiretroviral medications.
Side
effects have been reported frequently by persons taking antiretroviral
agents as PEP (15--23). In multiple instances, a substantial
(range: 17%--47%) proportion of HCP taking PEP after occupational
exposures to HIV-positive sources did not complete a full 4-week
course of therapy because of inability to tolerate the drugs
(15--17,19,20). Data from the National Surveillance System
for Health Care Workers (NaSH), CDC's occupational surveillance
system for occupational exposures and infections in hospitals, for
June 1995--December 2004 indicate that 401 (46.9%) of 921 HCP with
at least one follow-up visit after starting PEP experienced one
or more symptoms. The symptom reported most frequently was nausea
(26.5%), followed by malaise and fatigue (22.8%) (CDC, unpublished
data, 2005). Of 503 HCP who stopped HIV PEP prematurely (<28
days), 361 (24.0%) did so because of adverse effects of the drugs.
Similar data have been reported from the Italian Registry of Antiretroviral
Postexposure Prophylaxis, which includes data primarily on HCP taking
PEP but also collects data on those taking PEP after nonoccupational
exposures (18). In multivariate analysis, those taking regimens
that include PI were more likely to experience PEP-associated side
effects and to discontinue PEP prematurely (<28 days). Because
side effects are frequent and particularly because they are cited
as a major reason for not completing PEP regimens as prescribed,
the selection of regimens should be heavily influenced toward those
that are tolerable for short-term use.
In
addition, all approved antiretroviral agents might have potentially
serious drug interactions when used with certain other drugs, requiring
careful evaluation of concomitant medications, including over-the-counter
medications and supplements (e.g., herbals), used by an exposed
person before prescribing PEP and close monitoring for toxicity
of anyone receiving these drugs (24--33) (Tables
3--5).
PIs and NNRTIs have the greatest potential for interactions with
other drugs. Information regarding potential drug interactions has
been published (13,24--33). Additional information is included
in the manufacturers' package inserts. Because of interactions,
certain drugs should not be administered concomitantly with PIs
or with efavirenz (EFV) (Tables
4 and 5).
Consultation with a pharmacist might be considered.
Selection
of HIV PEP Regimens
Determining
which agents and how many to use or when to alter a PEP regimen
is primarily empiric (34). Guidelines for treating HIV infection,
a condition typically involving a high total body burden of HIV,
recommend use of three or more drugs (13,14); however, the
applicability of these recommendations to PEP is unknown. Among
HIV-infected patients, combination regimens with three or more antiretroviral
agents have proved superior to monotherapy and dual-therapy regimens
in reducing HIV viral load, reducing incidence of opportunistic
infections and death, and delaying onset of drug resistance (13,14).
In theory, a combination of drugs with activity at different stages
in the viral replication cycle (e.g., nucleoside analogues with
a PI) might offer an additive preventive effect in PEP, particularly
for occupational exposures that pose an increased risk for transmission
or for transmission of a resistant virus. Although use of a three-
(or more) drug regimen might be justified for exposures that pose
an increased risk for transmission, whether the potential added
toxicity of a third or fourth drug is justified for lower-risk exposures
is uncertain, especially in the absence of data supporting increased
efficacy of more drugs in the context of occupational PEP. Offering
a two-drug regimen is a viable option, primarily because the benefit
of completing a full course of this regimen exceeds the benefit
of adding the third agent and risking noncompletion (35).
In addition, the total body burden of HIV is substantially lower
among exposed HCP than among persons with established HIV infection.
For these reasons, the recommendations in this report provide guidance
for two- and three- (or more) drug PEP regimens on the basis of
the level of risk for HIV transmission represented by the exposure
(Tables
1 and 2; Appendix).
Resistance
to Antiretroviral Agents
Known
or suspected resistance of the source virus to antiretroviral agents,
particularly those that might be included in a PEP regimen, is a
concern for persons making decisions about PEP (36). Drug
resistance to all available antiretroviral agents has been reported,
and cross-resistance within drug classes is frequent (37).
Although occupational transmission of drug-resistant HIV strains
has been reported despite PEP with combination drug regimens (36,38--40),
the effect of exposure to a resistant virus on transmission and
transmissibility is not well understood.
Since
publication of the previous guidelines, an additional report of
an occupational HIV seroconversion despite combination HIV PEP has
been published (Table
6) (38), bringing the total number of reports worldwide
to six. The exposure was a percutaneous injury sustained by a nurse
performing a phlebotomy on a heavily treatment-experienced patient.
At the time of the exposure, the source patient was failing treatment
with stavudine (d4T), lamivudine (3TC), ritonavir (RTV), and saquinavir
(SQV) and had a history of previous treatment with zidovudine (ZDV)
and zalcitabine (ddC). Genotypic resistance testing performed within
1 month of the exposure suggested resistance to ZDV and 3TC. Phenotypic
testing confirmed resistance to 3TC but demonstrated relative susceptibility
to ZDV and d4T. The source virus demonstrated no evidence of resistance
to nevirapine (NVP) or other NNRTIs. The initial HIV PEP regimen
started within 95 minutes of the exposure was ZDV, 3TC, and indinavir.
The worker was referred to a hospital where the regimen was changed
within 6 hours of the exposure to didanosine (ddI), d4T, and NVP
because of concerns regarding possible drug resistance to certain
or all of the components of the initial PEP regimen. The exposed
worker stopped ddI after 8 days because of symptoms but continued
to take d4T and NVP, stopping at day 24 because of a generalized
macular pruritic rash and mild thrombocytopenia. Seroconversion
was documented at 3 months. Sequencing of viruses from the source
and exposed worker demonstrated their close relatedness. Virus from
the worker demonstrated the same resistance patterns as those in
the source patient. In addition, the worker's virus had a mutation
suggesting resistance to the NNRTI class (38).
Empiric
decisions regarding the presence of antiretroviral drug resistance
are often difficult because patients frequently take more than one
antiretroviral agent. Resistance should be suspected in a source
patient when clinical progression of disease or a persistently increasing
viral load or decline in CD4+ T-cell count occurs despite therapy,
or when no virologic response to therapy occurs. However, resistance
testing of the source virus at the time of an exposure is impractical
because the results will not be available in time to influence the
choice of the initial PEP regimen. No data suggest that modification
of a PEP regimen after resistance testing results become available
(usually 1--2 weeks) improves efficacy of PEP (41).
Antiretroviral
Drugs During Pregnancy
Data
regarding the potential effects of antiretroviral drugs on the developing
fetus or neonate are limited (3). Carcinogenicity and mutagenicity
are evident in certain in vitro screening tests for ZDV and all
other FDA-licensed NRTIs. The relevance of animal data to humans
is unknown; however, because teratogenic effects were reported among
primates at drug exposures similar to those representing human therapeutic
exposure, pregnant women should not use efavirenz (EFV). Indinavir
(IDV) is associated with infrequent side effects in adults (i.e.,
hyperbilirubinemia and renal stones) that could be problematic for
a newborn. Because the half-life of IDV in adults is short, these
concerns might be relevant only if the drug is administered shortly
before delivery. Other concerns regarding use of PEP during pregnancy
have been raised by reports of mitochondrial dysfunction leading
to neurologic disease and death among uninfected children whose
mothers had taken antiretroviral drugs to prevent perinatal HIV
transmission and of fatal and nonfatal lactic acidosis in pregnant
women treated throughout gestation with a combination of d4T and
ddI (3).
Management
of Occupational Exposure by Emergency Physicians
Although
PHS guidelines for the management of occupational exposures to HIV
were first published in 1985 (42), HCP often are not familiar
with these guidelines. Focus groups conducted among emergency department
(ED) physicians in 2002 indicated that of 71 participants, >95%
had not read the 2001 guidelines before being invited to participate
(43). All physicians participating in these focus groups
had managed occupational exposures to blood or body fluids. They
cited three challenges in exposure management most frequently: evaluation
of an unknown source patient or a source patient who refused testing,
inexperience in managing occupational HIV exposures, and counseling
of exposed workers in busy EDs.
Occupational
HIV Exposure Management and PEP Use in U.S. Hospitals
Analysis
of NaSH data for June 1995--December 2004 provides information regarding
the management of occupational exposure to HIV in a convenience
sample of 95 U.S. hospitals. These data indicate improved adherence
to PHS recommendations concerning use of HIV PEP after occupational
exposures. A total of 28,010 exposures to blood and body fluids
were reported by these hospitals (CDC, unpublished data, 2005).
For all 25,510 exposures with known sources, 1,350 (5.3%) were to
HIV-positive sources, 15,301 (60.0%) to HIV-negative sources, and
8,859 (34.7%) to sources of unknown HIV status. Of 1,350 HCP exposed
to a known HIV-positive source, 788 (58.4%) started PEP, and 317
(49%) of 647 for whom follow-up information was available took PEP
for >21 days. The overall median duration of HIV PEP after
exposure to an HIV-positive source was 27 days, increasing from
10 days in 1995 to 26.5 days in 2004; the overall median duration
of HIV PEP after exposure to an HIV-negative source was 2 days,
decreasing from 7.5 days in 1995 to 1 day in 2004. The use of rapid
HIV tests for evaluation of source patients has increased; during
1995--1997, none of 25 NaSH facilities used rapid HIV tests, whereas
in 2004, a total of 21 (84% ) did (CDC, unpublished data, 2005).
Rapid HIV tests could result in decreased use of PEP and spare personnel
both undue anxiety and adverse effects of antiretroviral PEP (44--47).
The annual median time to initiation of PEP was consistent (2 hours).
Of 1,350 HCP with exposures to HIV-positive sources, 909 (67.1%)
had at least one follow-up serologic test recorded, but only 289
(31.8%) had tests recorded at 4--6 months (CDC, unpublished data,
2005).
In
1996, of 24 HCP taking PEP after exposure to HIV-positive sources,
10 (42%) took a three-drug PEP regimen compared with 30 (76.9%)
of 39 in 2004 (CDC, unpublished data, 2005). After 227 HIV exposures
for which only a two-drug PEP regimen was recommended (i.e., the
exposure was to mucous membranes or skin or was a superficial percutaneous
injury and the source person did not have end-stage AIDS or acute
HIV illness), 104 (45.8%) HCP initiated a three-drug HIV PEP regimen.
The National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline)†
reports similar findings. PEPline staff recommended changing or
discontinuing PEP regimens for 45 (38%) of 118 exposures involving
source patients with known viral load or CD4 cell count concerning
which they were consulted during April 2002--March 2003 (48;
R. Goldschmidt, PEPline, personal communication, 2004). For 14 (11.9%)
HCP, the recommendation was to decrease the number of drugs in the
PEP regimens; for 22 (18.7%) HCP, the recommendation was to increase
the number of drugs; and for nine (7.6%), the recommendation was
to change the PEP regimen, keeping the same number of drugs.
Recommendations
for the Management of HCP Potentially Exposed to HIV
Top
Exposure
prevention remains the primary strategy for reducing occupational
bloodborne pathogen infections. However, occupational exposures
will continue to occur, and PEP will remain an important element
of exposure management.
HIV
PEP
The
recommendations provided in this report (Tables
1 and 2; Appendix)
apply to situations in which HCP have been exposed to a source person
who either has or is considered likely to have HIV infection. These
recommendations are based on the risk for HIV infection after different
types of exposure and on limited data regarding efficacy and toxicity
of PEP. If PEP is offered and taken and the source is later determined
to be HIV-negative, PEP should be discontinued. Although concerns
have been expressed regarding HIV-negative sources being in the
window period for seroconversion, no case of transmission involving
an exposure source during the window period has been reported in
the United States (39). Rapid HIV testing of source
patients can facilitate making timely decisions regarding use of
HIV PEP after occupational exposures to sources of unknown HIV status.
Because the majority of occupational HIV exposures do not result
in transmission of HIV, potential toxicity must be considered when
prescribing PEP. Because of the complexity of selecting HIV PEP
regimens, when possible, these recommendations should be implemented
in consultation with persons having expertise in antiretroviral
therapy and HIV transmission. Reevaluation of exposed HCP should
be strongly encouraged within 72 hours postexposure, especially
as additional information about the exposure or source person becomes
available.
Timing
and Duration of PEP
PEP
should be initiated as soon as possible, preferably within hours
rather than days of exposure. If a question exists concerning which
antiretroviral drugs to use, or whether to use a basic or expanded
regimen, the basic regimen should be started immediately rather
than delay PEP administration. The optimal duration of PEP is unknown.
Because 4 weeks of ZDV appeared protective in occupational and animal
studies, PEP should be administered for 4 weeks, if tolerated (49--52).
Recommendations
for the Selection of Drugs for HIV PEP
The
selection of a drug regimen for HIV PEP must balance the risk for
infection against the potential toxicities of the agent(s) used.
Because PEP is potentially toxic, its use is not justified for exposures
that pose a negligible risk for transmission (Tables
1 and 2).
The initial HIV PEP regimens recommended in these guidelines should
be viewed as suggestions that can be changed if additional information
is obtained concerning the source of the occupational exposure (e.g.,
possible treatment history or antiretroviral drug resistance) or
if expert consultation is provided. Given the complexity of choosing
and administering HIV PEP, whenever possible, consultation with
an infectious diseases consultant or another physician who has experience
with antiretroviral agents is recommended, but it should not delay
timely initiation of PEP.
Consideration
should be given to the comparative risk represented by the exposure
and information regarding the exposure source, including history
of and response to antiretroviral therapy based on clinical response,
CD4+ T-cell counts, viral load measurements, and current disease
stage. When the source person's virus is known or suspected to be
resistant to one or more of the drugs considered for the PEP regimen,
the selection of drugs to which the source person's virus is unlikely
to be resistant is recommended; expert consultation is advised.
If this information is not immediately available, initiation of
PEP, if indicated, should not be delayed; changes in the regimen
can be made after PEP has started, as appropriate. For HCP who initiate
PEP, re-evaluation of the exposed person should occur within 72
hours postexposure, especially if additional information about the
exposure or source person becomes available.
PHS
continues to recommend stratification of HIV PEP regimens based
on the severity of exposure and other considerations (e.g., concern
for antiretroviral drug resistance in the exposure source). The
majority of HIV exposures will warrant a two-drug regimen, using
two NRTIs or one NRTI and one NtRTI (Tables
1 and 2; Appendix).
Combinations that can be considered for PEP include ZDV and 3TC
or emtricitabine (FTC); d4T and 3TC or FTC; and tenofovir (TDF)
and 3TC or FTC. In the previous PHS guidelines, a combination of
d4T and ddI was considered one of the first-choice PEP regimens;
however, this regimen is no longer recommended because of concerns
about toxicity (especially neuropathy and pancreatitis) and the
availability of more tolerable alternative regimens (3).
The
addition of a third (or even a fourth) drug should be considered
for exposures that pose an increased risk for transmission or that
involve a source in whom antiretroviral drug resistance is likely.
The addition of a third drug for PEP after a high-risk exposure
is based on demonstrated effectiveness in reducing viral burden
in HIV-infected persons. However, no definitive data exist that
demonstrate increased efficacy of three- compared with two-drug
HIV PEP regimens. Previously, IDV, nelfinavir (NFV), EFV, or abacavir
(ABC) were recommended as first-choice agents for inclusion in an
expanded PEP regimen (3).
PHS
now recommends that expanded PEP regimens be PI-based. The PI preferred
for use in expanded PEP regimens is lopinavir/ritonavir (LPV/RTV).
Other PIs acceptable for use in expanded PEP regimens include atazanavir,
fosamprenavir, RTV-boosted IDV, RTV-boosted SQV, or NFV (Appendix).
Although side effects are common with NNRTIs, EFV may be considered
for expanded PEP regimens, especially when resistance to PIs in
the source person's virus is known or suspected. Caution is advised
when EFV is used in women of childbearing age because of the risk
of teratogenicity.
Drugs
that may be considered as alternatives to the expanded regimens,
with warnings about side effects and other adverse events, are EFV
or PIs as noted in the Appendix in combination with ddl and either
3TC or FTC. The fusion inhibitor enfuvirtide (T20) has theoretic
benefits for use in PEP because its activity occurs before viral-host
cell integration; however, it is not recommended for routine HIV
PEP because of the mode of administration (subcutaneous injection
twice daily). Furthermore, use of T20 has the potential for production
of anti-T20 antibodies that cross react with HIV gp41. This could
result in a false-positive, enzyme immunoassay (EIA) HIV antibody
test among HIV-uninfected patients. A confirmatory Western blot
test would be expected to be negative in such cases. T20 should
only be used with expert consultation.
Antiviral
drugs not recommended for use as PEP, primarily because of the higher
risk for potentially serious or life-threatening adverse events,
include ABC, delavirdine, ddC, and, as noted previously, the combination
of ddI and d4T. NVP should not be included in PEP regimens except
with expert consultation because of serious reported side effects,
including hepatotoxicty (with one instance of fulminant liver failure
requiring liver transplantation), rhabdomyolysis, and hypersensitivity
syndrome (53--55).
Because
of the complexity of selection of HIV PEP regimens, consultation
with persons having expertise in antiretroviral therapy and HIV
transmission is strongly recommended. Certain institutions have
required consultation with a hospital epidemiologist or infectious
diseases consultant when HIV PEP use is under consideration. This
can be especially important in management of a pregnant or breastfeeding
worker or a worker who has been exposed to a heavily treatment-experienced
source (Box
1).
Resources
for consultation are available from the following sources:
· PEPline
at http://www.ucsf.edu/hivcntr/Hotlines/PEPline;
telephone 888-448-4911;
· HIV
Antiretroviral Pregnancy Registry at http://www.apregistry.com/index.htm;
Address: Research Park, 1011 Ashes Drive, Wilmington, NC 28405.
Telephone: 800-258-4263; Fax: 800-800-1052; E-mail: registry@nc.crl.com;
· FDA
(for reporting unusual or severe toxicity to antiretroviral agents)
at http://www.fda.gov/medwatch;
telephone: 800-332-1088; address: MedWatch, HF-2, Food and Drug
Administration, 5600 Fishers Lane, Rockville, MD 20857;
· CDC
(for reporting HIV infections in HCP and failures of PEP) at telephone
800-893-0485; and
· HIV/AIDS
Treatment Information Service at http://aidsinfo.nih.gov.
Follow-Up
of Exposed HCP
Postexposure
Testing
HCP
with occupational exposure to HIV should receive follow-up counseling,
postexposure testing, and medical evaluation regardless of whether
they receive PEP. HIV-antibody testing by enzyme immunoassay should
be used to monitor HCP for seroconversion for >6 months after
occupational HIV exposure. After baseline testing at the time of
exposure, follow-up testing could be performed at 6 weeks, 12 weeks,
and 6 months after exposure. Extended HIV follow-up (e.g., for 12
months) is recommended for HCP who become infected with HCV after
exposure to a source coinfected with HIV and HCV. Whether extended
follow-up is indicated in other circumstances (e.g., exposure to
a source co-infected with HIV and HCV in the absence of HCV seroconversion
or for exposed persons with a medical history suggesting an impaired
ability to mount an antibody response to acute infection) is unclear.
Although rare instances of delayed HIV seroconversion have been
reported (56,57), the infrequency of this occurrence does
not warrant adding to exposed persons' anxiety by routinely extending
the duration of postexposure follow-up. However, this should not
preclude a decision to extend follow-up in a particular situation
based on the clinical judgment of the exposed person's health-care
provider. The routine use of direct virus assays (e.g., HIV p24
antigen EIA or tests for HIV ribonucleic acid) to detect infection
among exposed HCP usually is not recommended (58). Despite
the ability of direct virus assays to detect HIV infection a few
days earlier than EIA, the infrequency of occupational seroconversion
and increased costs of these tests do not warrant their routine
use in this setting. In addition, the relatively high rate of false-positive
results of these tests in this setting could lead to unnecessary
anxiety or treatment (59,60). Nevertheless, HIV testing should
be performed on any exposed person who has an illness compatible
with an acute retroviral syndrome, regardless of the interval since
exposure. A person in whom HIV infection is identified should be
referred for medical management to a specialist with expertise in
HIV treatment and counseling. Health-care providers caring for persons
with occupationally acquired HIV infection can report these cases
to CDC at telephone 800-893-0485 or to their state health departments.
Monitoring
and Management of PEP Toxicity
If
PEP is used, HCP should be monitored for drug toxicity by testing
at baseline and again 2 weeks after starting PEP. The scope of testing
should be based on medical conditions in the exposed person and
the toxicity of drugs included in the PEP regimen. Minimally, laboratory
monitoring for toxicity should include a complete blood count and
renal and hepatic function tests. Monitoring for evidence of hyperglycemia
should be included for HCP whose regimens include any PI; if the
exposed person is receiving IDV, monitoring for crystalluria, hematuria,
hemolytic anemia, and hepatitis also should be included. If toxicity
is noted, modification of the regimen should be considered after
expert consultation; further diagnostic studies might be indicated.
Exposed
HCP who choose to take PEP should be advised of the importance of
completing the prescribed regimen. Information should be provided
about potential drug interactions and drugs that should not be taken
with PEP, side effects of prescribed drugs, measures to minimize
side effects, and methods of clinical monitoring for toxicity during
the follow-up period. HCP should be advised that evaluation of certain
symptoms (e.g., rash, fever, back or abdominal pain, pain on urination
or blood in the urine, or symptoms of hyperglycemia (e.g., increased
thirst or frequent urination) should not be delayed.
HCP
often fail to complete the recommended regimen often because they
experience side effects (e.g., nausea or diarrhea). These symptoms
often can be managed with antimotility and antiemetic agents or
other medications that target specific symptoms without changing
the regimen. In other situations, modifying the dose interval (i.e.,
administering a lower dose of drug more frequently throughout the
day, as recommended by the manufacturer) might facilitate adherence
to the regimen. Serious adverse events§ should be reported
to FDA's MedWatch program.
Although
recommendations for follow-up testing, monitoring, and counseling
of exposed HCP are unchanged from those published previously (3),
greater emphasis is needed on improving follow-up care provided
to exposed HCP (Box
2). This might result in increased adherence to HIV PEP regimens,
better management of associated symptoms with ancillary medications
or regimen changes, improved detection of serious adverse effects,
and serologic testing among a larger proportion of exposed personnel
to determine if infection is transmitted after occupational exposures.
Closer follow-up should in turn reassure HCP who become anxious
after these events (61,62). The psychologic impact on HCP
of needlesticks or exposure to blood or body fluid should not be
underestimated. Providing HCP with psychologic counseling should
be an essential component of the management and care of exposed
HCP.
Reevaluation and Updating of HIV PEP Guidelines
As
new antiretroviral agents for treatment of HIV infection and additional
information concerning early HIV infection and prevention of HIV
transmission become available, the PHS Interagency Working Group
will assess the need to update these guidelines. Updates will be
published periodically as appropriate.
Acknowledgments
David
K. Henderson, MD, National Institutes of Health, Bethesda, Maryland;
Kimberly A. Struble, PharmD, Food and Drug Administration, Rockville,
Maryland; and Abe Macher, MD, Health Resources and Services Administration,
Rockville, Maryland, assisted in the preparation of this report.
10/03/05
References
Scroll
down to list of references 1-62 at the following link: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5409a1.htm
Post
Exposure Prophylaxis (PEP)
and
Non-occupational Post Exposure Prophylaxis (NPEP)
Articles on HIVandHepatitis.com
TDF+3TC+d4T
Is Significantly Better Tolerated Than ZDV+3TC or ZDV+3TC+NFV as
Non-occupational HIV Post-exposure Prophylaxis and Results
in Improved Adherence
-
5/27/05
Combivir Plus PI Kaletra HIV Prophylaxis
May Increase Tolerability -
2/04/05
CDC
Issues Guidelines for Use of Anti-HIV Drugs After HIV Exposure
Through Sex, Injection Drug Use or Other High Risk Behaviors or
Circumstances
-
1/19/05
Tolerance
of a Short Course of Nevirapine, Associated with 2 Nucleoside Analogues,
in Postexposure Prophylaxis of HIV -
1/10/05
Tolerance
of a Short Course of Nevirapine Plus Two Nucleoside Analogues in
Postexposure Prophylaxis of HIV-
11/29/04
Two Drugs or Three in Postexposure
Prophylaxis for Occupational Exposure to HIV? - 08/27/04
Dual Agent HIV Prophylaxis
Is Preferable After Needle Sticks - 08/04/04
Safety
and Tolerability of Non-occupational Post-exposure Prophylaxis
(NPEP) - 07/28/04
The
European Non Occupational Post-exposure Prophylaxis (NONOPEP)
Registry -
07/21/04
HIV Postexposure
Prophylaxis Does Not Increase High-risk Behaviors - 05/28/04
HIV Postexposure Prophylaxis in
Adolescents - 05/03/04
HIV Postexposure Prophylaxis (PEP)
Is Cost-effective by Conventional Standards and Cost-saving for
Persons Seeking PEP After Male to Male Receptive Anal Intercourse
02/02/04
Postexposure HIV Prophylaxis Is Cost-effective
Outside Occupational Setting
01/16/04
UCSF Begins Study Testing Viread (tenofovir)
to Prevent HIV Infection
09/19/03
Postexposure Prophylaxis (PEP)
to Prevent HIV Infection in Adolescents
08/06/03
Caution Advised in Antiretroviral
Use for Children after Possible HIV Exposure
06/06/03
Revisiting the Public Health Service
Guidelines for Occupational Exposure to the Blood-borne Viruses
Hepatitis B, Hepatitis C and HIV
05/09/03
In Vitro Model Could Be Used to Assess
HIV Postexposure Prophylaxis
12/02/02
Kaletra/Combivir Lowers Side Effects
of Postexposure HIV Prophylaxis
10/02/02
Medical Team Approach to Treatment
of Rape Victims Improves Adherence to Post Exposure Prophylaxis
(PEP)
09/25/02
Source Testing Cuts Need for HIV Postexposure
Prophylaxis
06/03/02
Recommendations for Post-Exposure
Prophylaxis (PEP) for Exposure to HBV, HCV or HIV
1/07/02
Most Junior Physicians Have Poor Knowledge
of PEP for HIV
1/07/02
Effective PEP After HIV Exposure Requires
Source Identification
01/04/02
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