|
Updated
U.S. Public Health Service Guidelines for the Management of
Occupational
Exposures to HBV, Hepatitis C Virus, and HIV and Recommendations
for
Postexposure Prophylaxis: June 2001
Table
of Contents
Summary
Introduction
Definitions of Health-Care Workers and Exposure
Background
Occupational Transmission of HBV
Occupational Transmission of Hepatitis C Virus
Occupational Transmission of HIV
Recommendations for the Management of HCP Potentially
Exposed to HBV, Hepatitis C Virus, or HIV
Hepatitis B Vaccination
Treatment of an Exposure Site
Exposure Report
Evaluation of the Exposure and the Exposure Source
Management of Exposures to HBV
Management of Exposures to Hepatitis C Virus
Management of Exposures to HIV
Recommendations for the Selection of Drugs for HIV PEP
Occupational Exposure Management Resources
References
Appendices
Appendix A
Appendix B
Appendix C
Table 1. Reported instances of failure of combination
drug postexposure prophylaxis to prevent
HIV infection in health-care personnel exposed to
HIV-infected blood
Table 2. Primary side effects associated with
antiretroviral agents
Table 3. Recommended postexposure prophylaxis for
exposure to hepatitis B virus
Table 4. Recommended HIV postexposure prophylaxis for
percutaneous injuries
Table 5. Recommended HIV postexposure prophylaxis for
mucous membrane exposures and
nonintact skin* exposures
Reprinted
from the MMWR June 29, 2001/ 50(RR-11);1-42
The
MMWR series of publications is published by the Epidemiology
Program Office, Centers for
Disease
Control and Prevention (CDC), U.S. Department of Health and
Human Services,
Atlanta,
GA 30333.
Centers
for Disease Control and Prevention
Jeffrey
P. Koplan, M.D., M.P.H.
Director
The
material in this report was prepared for publication
by
National Center for Infectious Diseases
James
H. Hughes, M.D.
Director
Division
of Healthcare Quality Promotion
Julie
L. Gerberding, M.D.,
M.P.H.
Director
Division
of Viral Hepatitis (Proposed)
Harold
S. Margolis, M.D.
Acting
Director
Division
of AIDS, STD, and TB Laboratory Research
Harold
W. Jaffe, M.D.
Director
National
Center for HIV, STD, and TB Prevention
Helene
D. Gayle, M.D., M.PH.
Director
Division
of HIV/AIDS Prevention Surveillance and
Epidemiology
Robert
S. Janssen, M.D.
Director
National
Institute for Occupational Safety and Health
Kathleen
Rest, Ph.D.
Acting
Director
Division
of Surveillance, Hazard Evaluations, and Field
Studies
R.
Delon Hull, Ph.D.
Acting
Director
This
report was produced as an MMWR serial
publication
in Epidemiology Program Office
Stephen
B. Thacker, M.D., M.Sc.
Director
Office
of Scientific and Health Communications
John
W. Ward, M.D.
Director
Editor,
MMWR Series
CDC
Surveillance Summaries
Suzanne
M. Hewitt, M.P.A.
Managing
Editor
Patricia
A. McGee
Project
Editor
Lynda
G. Cupell and Morie M.
Higgins
Visual
Information Specialists
Michele
D. Renshaw and Erica R.
Shaver
Information
Technology
Specialists
The
following CDC staff members prepared this report:
Elise
M. Beltrami, M.D.
Francisco
Alvarado-Ramy, M.D.
Sara
E. Critchley, R.N.
Adelisa
L. Panlilio, M.D., M.P.H.
Denise
M. Cardo, M.D.
Division
of Healthcare Quality Promotion
National
Center for Infectious Diseases
William
A. Bower, M.D.
Miriam
J. Alter, Ph.D.
Division
of Viral Hepatitis*
National
Center for Infectious Diseases
Jonathan
E. Kaplan, M.D.
Division
of AIDS, STD, and TB Laboratory Research
National
Center for Infectious Diseases
and
Division
of HIV/AIDS Prevention
National
Center for HIV, STD, and TB Prevention
Boris
Lushniak, M.D., M.P.H.
Division
of Surveillance, Hazard Evaluations, and Field Studies
National
Institute for Occupational Safety and Health
in
collaboration with
David
K. Henderson, M.D.
National
Institutes of Health
Kimberly
A. Struble, Pharm.D.
Food
and Drug Administration
Abe
Macher, M.D.
Health
Resources and Services Administration
*Proposed.
Summary
This
report updates and consolidates all previous 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
hepatitis B virus
(HBV),
hepatitis C virus (Hepatitis C Virus), or human immunodeficiency virus
(HIV).
Recommendations
for HBV postexposure management include initiation of the
hepatitis B
vaccine
series to any susceptible, unvaccinated person who sustains an
occupational
blood
or body fluid exposure. Postexposure prophylaxis (PEP) with
hepatitis B immune
globulin
(HBIG) and/or hepatitis B vaccine series should be considered
for occupational
exposures
after evaluation of the hepatitis B surface antigen status of
the source and the
vaccination
and vaccine-response status of the exposed person. Guidance is
provided to
clinicians
and exposed HCP for selecting the appropriate HBV PEP.
Immune
globulin and antiviral agents (e.g., interferon with or
without ribavirin) are not
recommended
for PEP of hepatitis C. For Hepatitis C Virus postexposure management, the
Hepatitis C Virus status
of the source and the exposed person should be determined, and
for HCP exposed to
an Hepatitis C Virus positive source, follow-up Hepatitis C Virus testing should be
performed to determine if infection
develops.
Recommendations
for HIV PEP include a basic 4-week regimen of two drugs (zidovudine
[ZDV]
and lamivudine [3TC]; 3TC and stavudine [d4T]; or didanosine [ddI]
and d4T)
for
most HIV exposures and an expanded regimen that includes the
addition of a third
drug
for HIV exposures that pose an increased risk for
transmission. 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.
In
addition, this report outlines several special circumstances
(e.g., delayed exposure
report,
unknown source person, pregnancy in the exposed person,
resistance of the source
virus
to antiretroviral agents, or toxicity of the PEP regimen) when
consultation with
local
experts and/or the National Clinicians' Post-Exposure
Prophylaxis Hotline
([PEPline]
1-888-448-4911) is advised.
Occupational
exposures should be considered urgent medical concerns to
ensure timely
postexposure
management and administration of HBIG, hepatitis B vaccine,
and/or HIV
PEP.
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to Top
Introduction
Avoiding
occupational blood exposures is the primary way to prevent
transmission of hepatitis B
virus
(HBV), hepatitis C virus (Hepatitis C Virus), and human immunodeficiency
virus (HIV) in health-care
settings
(1). However, hepatitis B immunization and postexposure
management are integral
components
of a complete program to prevent infection fol-lowing
bloodborne pathogen
exposure
and are important elements of workplace safety (2).
The
U.S. Public Health Service (PHS) has published previous
guidelines for the man-agement of
HIV
exposures that included considerations for postexposure
prophylaxis (PEP) (35). Since
publication
of the 1998 HIV exposure guidelines (5), several new
antiretroviral agents have been
approved
by the Food and Drug Administration (FDA), and more
information is available about
the
use and safety of HIV PEP (611). In addition, questions
exist regarding considerations
about
PEP regimens when the source person's virus is known or
suspected to be resistant to one
or
more of the antiretroviral agents that might be used for PEP.
Concern also has arisen about
the
use of PEP when it is not warranted. Data indicate that some
health-care personnel (HCP)
take
a full course of HIV PEP after exposures that do not confer an
HIV transmission risk
(10,11).
In
September 1999, a meeting of a PHS interagency working group*
and expert consultants
was
convened by CDC. The PHS working group decided to issue
updated recommendations
for
the management of occupational exposure to HIV. In addition,
the report was to include
recommendations
for the management of occupational HBV and Hepatitis C Virus exposures so
that a single
document
could comprehensively address the manage-ment of occupational
exposures to
bloodborne
pathogens. This report updates and con-solidates the previous
PHS guidelines and
recommendations
for occupational HBV, Hepatitis C Virus, and HIV exposure management for HCP.
Specific
practice recommendations for the management of occupational
bloodborne pathogen
exposures
are outlined to assist health-care institutions with the
implementation of these PHS
guidelines
(Appendices A and B). As relevant information becomes
available, updates of these
recommendations
will be published. Recommendations for nonoccupational (e.g.,
sexual,
pediatric,
and perinatal) HBV, Hepatitis C Virus, and HIV exposures are not addressed
in these guidelines
and
can be found elsewhere (1215).
*This
interagency working group comprised representatives of CDC,
the Food and Drug Administration (FDA), the Health Resources
and Services Administration, and the National Institutes of
Health. Information included in these recommendations may not
represent FDA approval or approved labeling for the particular
product or indications in question. Specifically, the terms
"safe" and "effective" may not be
synonymous with the FDA-defined legal standards for product
approval.
Return
to Top
Definitions
Of Health-Care Workers And Exposure
In
this report, health-care personnel (HCP) are defined as
persons (e.g., employees, students,
contractors,
attending clinicians, public-safety workers , or volunteers)
whose activities involve
contact
with patients or with blood or other body fluids from patients
in a health-care,
laboratory,
or public-safety setting. The potential exists for blood and
body fluid exposure to
other
workers, and the same principles of exposure management could
be applied to other
settings.
An
exposure that might place HCP at risk for HBV, Hepatitis C Virus, or 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 (16,17).
In
addition to blood and body fluids containing visible blood,
semen and vaginal secre-tions also
are
considered potentially infectious. Although semen and vaginal
secretions have been
implicated
in the sexual transmission of HBV, Hepatitis C Virus, and 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 HBV, Hepatitis C Virus, and
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 contain blood. The
risk
for transmission of HBV, Hepatitis C Virus, and HIV infection from these
fluids and materials is
extremely
low.
Any
direct contact (i.e., contact without barrier protection) to
concentrated virus in a research
laboratory
or production facility is considered an exposure that requires
clinical evaluation. For
human
bites, the 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 HBV or
HIV
infection only rarely has been reported by this route
(1820) (CDC, unpublished data,
1998).
This
section provides the rationale for the postexposure management
and prophy-laxis
recommendations
presented in this report. Additional details concerning the
risk for occupational
bloodborne
pathogen transmission to HCP and management of occupa-tional
bloodborne
pathogen
exposures are available elsewhere (5,12,13,21-24).
Occupational
Transmission of HBV
Risk
for Occupational Transmission of HBV
HBV
infection is a well recognized occupational risk for HCP (25).
The risk of HBV infection is
primarily
related to the degree of contact with blood in the work place
and also to the hepatitis B
e
antigen (HBeAg) status of the source person. In studies of HCP
who sustained injuries from
needles
contaminated with blood containing HBV, the risk of developing
clinical hepatitis if the
blood
was both hepatitis B surface antigen (HBsAg)-and HBeAg-positive
was 22%31%; the
risk
of developing serologic evidence of HBV infection was
37%62%. By comparison, the risk
of
developing clinical hepatitis from a needle contaminated with
HBsAg-positive,
HBeAg-negative
blood was 1%6%, and the risk of developing serologic
evidence of HBV
infection,
23%37% (26).
Although
percutaneous injuries are among the most efficient modes of
HBV trans-mission, these
exposures
probably account for only a minority of HBV infections among
HCP. In several
investigations
of nosocomial hepatitis B outbreaks, most infected HCP could
not recall an overt
percutaneous
injury (27,28), although in some studies, up to one third of
infected HCP recalled
caring
for a patient who was HBsAg-positive (29,30). In addition, HBV
has been demonstrated
to
survive in dried blood at room temperature on environmental
surfaces for at least 1 week
(31).
Thus, HBV infections that occur in HCP with no history of
nonoccupational exposure or
occupational
percutaneous injury might have resulted from direct or
indirect blood or body fluid
exposures
that inoculated HBV into cutaneous scratches, abrasions,
burns, other lesions, or on
mucosal
surfaces (32 34). The potential for HBV transmission
through contact with
environmental
surfaces has been demonstrated in investigations of HBV
outbreaks among
patients
and staff of hemodialysis units (3537).
Blood
contains the highest HBV titers of all body fluids and is the
most important vehicle of
transmission
in the health-care setting. HBsAg is also found in several
other body fluids, including
breast
milk, bile, cerebrospinal fluid, feces, nasopharyngeal
washings, saliva, semen, sweat, and
synovial
fluid (38). However, the concentration of HBsAg in body fluids
can be 1001000σfold
higher
than the concentration of infectious HBV particles. Therefore,
most body fluids are not
efficient
vehicles of transmission because they contain low quantities
of infectious HBV, despite
the
presence of HBsAg.
In
serologic studies conducted in the United States during the
1970s, HCP had a prevalence of
HBV
infection approximately 10 times higher than the general
population (3942). Because of
the
high risk of HBV infection among HCP, routine preexposure
vaccination of HCP against
hepatitis
B and the use of standard precautions to prevent exposure to
blood and other
potentially
infectious body fluids have been recommended since the early
1980s (43).
Regulations
issued by the Occupational Safety and Health Administration (OSHA)
(2) have
increased
compliance with these recommendations. Since the
implementation of these
recommendations,
a sharp decline has occurred in the incidence of HBV infection
among HCP.
PEP
for HBV
Efficacy
of PEP for HBV. The effectiveness of hepatitis B immune
globulin (HBIG) and/ or
hepetitis
B vaccine in various postexposure settings has been evaluated
by prospec-tive studies.
For
perinatal exposure to an HBsAg-, HBeAg-positive mother, a
regimen combining HBIG and
initiation
of the hepatitis B vaccine series at birth is 85%95%
effective in preventing HBV
infection
(44,45). Regimens involving either multiple doses of HBIG
alone or the hepatitis B
vaccine
series alone are 70%75% effective in prevent-ing HBV
infection (46). In the
occupational
setting, multiple doses of HBIG initiated within 1 week
following percutaneous
exposure
to HBsAg-positive blood provides an estimated 75% protection
from HBV infection
(4749).
Although the postexposure efficacy of the combination of HBIG
and the hepatitis B
vaccine
series has not been evaluated in the occupational setting, the
increased efficacy of this
regimen
observed in the perinatal setting, compared with HBIG alone,
is presumed to apply to
the
occupational setting as well. In addition, because persons
requiring PEP in the occupational
setting
are generally at continued risk for HBV exposure, they should
receive the hepatitis B
vaccine
series.
Safety
of PEP for HBV. Hepatitis B vaccines have been found to be
safe when admin-istered
to
infants, children, or adults (12,50). Through the year 2000,
approximately 100 million persons
have
received hepatitis B vaccine in the United States. The most
com-mon side effects from
hepatitis
B vaccination are pain at the injection site and mild to
moderate fever (5055). Studies
indicate
that these side effects are reported no more frequently among
persons vaccinated than
among
those receiving placebo (51,52). Approximately 45 reports have
been received by the
Vaccine
Adverse Event Report-ing System (VAERS) of alopecia (hair
loss) in children and
adults
after administration of plasma-derived and recombinant
hepatitis B vaccine; four persons
sustained
hair loss following vaccination on more than one occasion
(56). Hair loss was
temporary
for approximately two thirds of persons who experienced hair
loss. An epidemiologic
study
conducted in the Vaccine Safety Datalink found no statistical
association between
alope-cia
and receipt of hepatitis B vaccine in children (CDC,
unpublished data, 1998). A low
rate
of anaphylaxis has been observed in vaccine recipients based
on reports to VAERS; the
estimated
incidence is 1 in 600,000 vaccine doses distributed. Although
none of the persons
who
developed anaphylaxis died, anaphylactic reactions can be
life-threaten-ing; therefore,
further
vaccination with hepatitis B vaccine is contraindicated in
persons with a history of
anaphylaxis
after a previous dose of vaccine.
Hepatitis
B immunization programs conducted on a large scale in Taiwan,
Alaska, and New
Zealand
have observed no association between vaccination and the
occurrence of serious
adverse
events. Furthermore, in the United States, surveillance of
adverse events following
hepatitis
B vaccination has demonstrated no association between
hepatitis B vaccine and the
occurrence
of serious adverse events, including Guillain-BarrΘ syn-drome,
transverse myelitis,
multiple
sclerosis, optic neuritis, and seizures (5759) (CDC,
unpublished data, 1991).
However,
several case reports and case series have claimed an
association between hepatitis B
vaccination
and such syndromes and diseases as mul-tiple sclerosis, optic
neuritis, rheumatoid
arthritis,
and other autoimmune diseases (57,60 66). Most of these
reported adverse events
have
occurred in adults, and no report has compared the frequency
of the purported
vaccine-associated
syndrome/disease with the frequency in an unvaccinated
population. In
addition,
recent case-control studies have demonstrated no association
between hepatitis B
vaccination
and development or short-term risk of relapse of multiple
sclerosis (67,68), and
reviews
by international panels of experts have concluded that
available data do not demonstrate
a
causal asso-ciation between hepatitis B vaccination and
demyelinating diseases, including
multiple
sclerosis (69).
HBIG
is prepared from human plasma known to contain a high titer of
antibody to HBsAg
(anti-HBs).
The plasma from which HBIG is prepared is screened for HBsAg
and antibodies to
HIV
and Hepatitis C Virus. The process used to prepare HBIG inactivates and
eliminates HIV from the final
product.
Since 1996, the final product has been free of Hepatitis C Virus RNA as
determined by the
polymerase
chain reaction (PCR), and, since 1999, all products avail-able
in the United States
have
been manufactured by methods that inactivate Hepatitis C Virus and other
viruses. No evidence exists
that
HBV, Hepatitis C Virus, or HIV have ever been transmitted by HBIG
commercially available in the
United
States (70,71).
Serious
adverse effects from HBIG when administered as recommended
have been rare. Local
pain
and tenderness at the injection site, urticaria and angioedema
might occur; anaphylactic
reactions,
although rare, have been reported following the injection of
human immune globulin
(IG)
preparations (72). Persons with a history of anaphylactic
reaction to IG should not receive
HBIG.
PEP
for HBV During Pregnancy. No apparent risk exists for adverse
effects to devel-oping
fetuses
when hepatitis B vaccine is administered to pregnant women (CDC,
unpub-lished data,
1990).
The vaccine contains noninfectious HBsAg particles and should
pose no risk to the fetus.
HBV
infection during pregnancy might result in severe disease for
the mother and chronic
infection
for the newborn. Therefore, neither pregnancy nor lacta-tion
should be considered a
contraindication
to vaccination of women. HBIG is not con-traindicated for
pregnant or lactating
women.
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Occupational
Transmission of Hepatitis C Virus
Risk
for Occupational Transmission of Hepatitis C Virus
Hepatitis C Virus
is not transmitted efficiently through occupational exposures
to blood. The aver-age
incidence
of anti-Hepatitis C Virus seroconversion after accidental percutaneous
exposure from an
Hepatitis C Virus-positive
source is 1.8% (range: 0%7%) (7376), with one study
indicating that
transmission
occurred only from hollow-bore needles compared with other
sharps (75).
Transmission
rarely occurs from mucous membrane exposures to blood, and no
trans-mission in
HCP
has been documented from intact or nonintact skin exposures to
blood (77,78). Data are
limited
on survival of Hepatitis C Virus in the environment. In contrast to HBV, the
epidemiologic data for
Hepatitis C Virus
suggest that environmental contamination with blood con-taining
Hepatitis C Virus is not a significant
risk
for transmission in the health-care setting (79,80), with the
possible exception of the
hemodialysis
setting where Hepatitis C Virus transmission related to environmental
contamination and poor
infection-control
practices have been impli-cated (8184). The risk for
transmission from
exposure
to fluids or tissues other than Hepatitis C Virus-infected blood also has
not been quantified but is
expected
to be low.
Postexposure
Management for Hepatitis C Virus
In
several studies, researchers have attempted to assess the
effectiveness of IG following
possible
exposure to non-A, non-B hepatitis. These studies have been
difficult to interpret
because
they lack uniformity in diagnostic criteria and study design,
and, in all but one study, the
first
dose of IG was administered before potential exposure
(48,85,86). In an experiment
designed
to model Hepatitis C Virus transmission by needlestick exposure in the
health-care setting, high
anti-Hepatitis C Virus
titer IG administered to chimpanzees 1 hour after exposure to
Hepatitis C Virus-positive blood
did
not prevent transmission of infection (87). In 1994, the
Advisory Committee on
Immunization
Practices (ACIP) reviewed available data re-garding the
prevention of Hepatitis C Virus
infection
with IG and concluded that using IG as PEP for hepatitis C was
not supported (88).
This
conclusion was based on the following facts:
No protective antibody response has been identified
following Hepatitis C Virus infection.
Previous studies of IG use to prevent posttransfusion
non-A, non-B hepatitis might not be
relevant in making recommendations regarding PEP for
hepatitis C.
Experimental studies in chimpanzees with IG containing
anti-Hepatitis C Virus failed to prevent
transmission of infection after exposure.
No
clinical trials have been conducted to assess postexposure use
of antiviral agents (e.g.,
interferon
with or without ribavirin) to prevent Hepatitis C Virus infection, and
antivirals are not
FDA-approved
for this indication. Available data suggest that an
established infection might need
to
be present before interferon can be an effective treatment.
Kinetic studies suggest that the
effect
of interferon on chronic Hepatitis C Virus infection occurs in two phases.
During the first phase,
interferon
blocks the production or release of virus from infected cells.
In the second phase, virus
is
eradicated from the infected cells (89); in this later phase,
higher pretreatment alanine
aminotransferase
(ALT) levels correlate with an increasing decline in infected
cells, and the
rapidity
of the decline correlates with viral clearance. In contrast,
the effect of antiretrovirals
when
used for PEP after exposure to HIV is based on inhibition of
HIV DNA synthesis early in
the
retroviral replicative cycle.
In
the absence of PEP for Hepatitis C Virus, recommendations for postexposure
management are intended
to
achieve early identification of chronic disease and, if
present, referral for evaluation of
treatment
options. However, a theoretical argument is that intervention
with antivirals when Hepatitis C Virus
RNA
first becomes detectable might prevent the development of
chronic infection. Data from
studies
conducted outside the United States suggest that a short
course of interferon started early
in
the course of acute hepatitis C is associated with a higher
rate of resolved infection than that
achieved
when therapy is begun after chronic hepatitis C has been well
established (9092).
These
studies used various treat-ment regimens and included persons
with acute disease whose
peak
ALT levels were 5001,000 IU/L at the time therapy was
initiated (2.64 months after
exposure).
No
studies have evaluated the treatment of acute infection in
persons with no evi-dence of liver
disease
(i.e., Hepatitis C Virus RNA-positive <6 months duration with normal ALT
lev-els); among patients
with
chronic Hepatitis C Virus infection, the efficacy of antivirals has been
demonstrated only among patients
who
also had evidence of chronic liver disease (i.e., abnormal ALT
levels). In addition, treatment
started
early in the course of chronic Hepatitis C Virus infection (i.e., 6 months
after onset of infection) might
be
as effective as treatment started during acute infection (13).
Because 15%25% of patients
with
acute Hepatitis C Virus infection spontaneously resolve their infection
(93), treatment of these patients
during
the acute phase could expose them unnecessarily to the
discomfort and side effects of
antiviral
therapy.
Data
upon which to base a recommendation for therapy of acute
infection are insuf-ficient
because
a) no data exist regarding the effect of treating patients
with acute infec-tion who have
no
evidence of disease, b) treatment started early in the course
of chronic infection might be just
as
effective and would eliminate the need to treat persons who
will spontaneously resolve their
infection,
and c) the appropriate regimen is unknown.
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Occupational
Transmission of HIV
Risk
for Occupational Transmission of HIV
In
prospective studies of HCP, the average risk of HIV
transmission after a percutane-ous
exposure
to HIV-infected blood has been estimated to be approximately
0.3% (95% confidence
interval
[CI] = 0.2%0.5%) (94) and after a mucous membrane exposure,
approximately 0.09%
(95%
CI = 0.006%0.5%) (95). Although episodes of HIV
transmis-sion after nonintact skin
exposure
have been documented (96), 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
(97). 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 (98).
As
of June 2000, CDC had received voluntary reports of 56 U.S.
HCP with docu-mented HIV
seroconversion
temporally associated with an occupational HIV exposure. An
additional 138
episodes
in HCP are considered possible occupational HIV transmis-sions.
These workers had
a
history of occupational exposure to blood, other infectious
body fluids, or laboratory solutions
containing
HIV, and no other risk for HIV infection was identified, but
HIV seroconversion after
a
specific exposure was not documented (99).
Epidemiologic
and laboratory studies suggest that several factors might
affect the risk of HIV
transmission
after an occupational exposure. In a retrospective
case-control study of HCP who
had
percutaneous exposure to HIV, the risk for HIV infection was
found to be increased with
exposure
to a larger quantity of blood from the source person as
indicated by a) a device visibly
contaminated
with the patient's blood, b) a procedure that involved a
needle being placed
directly
in a vein or artery, or c) a deep injury (100). 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 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 (101).
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 trans-mit 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.
Some
evidence exists regarding host defenses possibly influencing
the risk for HIV infection. A
study
of HIV-exposed but uninfected HCP demonstrated an HIV-specific
cyto-toxic
T-lymphocyte
(CTL) response when peripheral blood mononuclear cells were
stimu-lated in
vitro
with HIV-specific antigens (102). Similar CTL responses have
been observed in other
groups
who experienced repeated HIV exposure without resulting
infection (103108). Among
several
possible explanations for this observation is that the host
immune response sometimes
might
prevent establishment of HIV infection after a per-cutaneous
exposure; another is that the
CTL
response simply might be a marker for exposure. In a study of
20 HCP with occupational
exposure
to HIV, a comparison was made of HCP treated with zidovudine (ZDV)
PEP and
those
not treated. The findings from this study suggest that ZDV
blunted the HIV-specific CTL
response
and that PEP might inhibit early HIV replication (109).
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