Download Occupational Exposure

林口長庚醫院 內科部 感染醫學科
吳丁樹 醫師
一位23歲林姓護士在照顧一位末期愛滋
病人時不慎被IC針所刺傷食指
 請問如何處理?
 需要吃抗病毒藥物嗎?
 吃幾種藥物?
 吃多久?

Post-exposure prophylaxis (PEP)
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Definitions
Exposures
Risks
Timing and duration of PEP
Selection of HIV PEP Regimens
Special issue in pregnancy
Follow-up
Post-contact seroconversion in HCWs
Infection control strategies
Definition

Health-care personnel (HCP) : all paid
and unpaid persons working in healthcare 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).
Exposures
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.
 Visibly bloody body fluids, semen and
vaginal secretions also are considered
potentially infectious

Exposures
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.
 Feces, nasal secretions, saliva, sputum,
sweat, tears, urine, and vomitus are not
considered potentially infectious unless
they are visibly bloody.

Janeway’s Immunobiology 7/e
Risks
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the average risk for HIV transmission after a
percutaneous exposure to HIV-infected blood
has been estimated to be approximately 0.3%
after a mucous membrane exposure,
approximately 0.09%
larger quantity of blood
 a device (e.g., a needle) visibly contaminated with
the patient’s blood
 a procedure that involved a needle being placed
directly in a vein or artery
 a deep injury
 Terminal HIV-related illness in the source patient.
Controversy

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
Timing and Duration of PEP
as soon as possible, preferably within hours
rather than days of exposure
 Because 4 weeks of ZDV appeared
protective in occupational and animal
studies, PEP should be administered for 4
weeks, if tolerated.
 Reevaluation of exposed HCP should be
strongly encouraged within 72 hours
postexposure, especially as additional
information about the exposure or source
person becomes available.

Science. 1995 Nov 17;270(5239):1197-9.
Prevention of SIV Infection in Macaques by (R)-9-(2Phosphonylmethoxypropyl)adenine
 Che-Chung Tsai (1), Kathryn E. Follis, Alexander
Sabo, Thomas W. Beck, Richard F. Grant, Norbert
Bischofberger, Raoul E. Benveniste, Roberta Black
 The efficacy of pre- and postexposure treatment with the antiviral
compound (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA)
was tested against simian immunodeficiency virus (SIV) in
macaques as a model for human immunodeficiency virus (HIV).
PMPA was administered subcutaneously once daily beginning
either 48 hours before, 4 hours after, or 24 hours after virus
inoculation. Treatment continued for 4 weeks and the virologic,
immunologic, and clinical status of the macaques was monitored for
up to 56 weeks. PMPA prevented SIV infection in all macaques
without toxicity, whereas all control macaques became infected.
These results suggest a potential role for PMPA prophylaxis against
early HIV infection in cases of known exposure.
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Tenofovir
Selection of HIV PEP Regimens
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2 drugs or 3 drugs?
The main arguments in favour of two-drug PEP
(fewer side effects, better adherence and course
completion rates) are being addressed through
switching to better-tolerated agents with lower pill
burdens.
At the same time, a potent three-drug PEP
regimen is preferred because resistance to
antiretroviral drugs is found at significant levels in
both treated and untreated infected individuals in
the UK.
Selection of HIV PEP Regimens
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the source of the occupational exposure (e.g.,
possible treatment history or antiretroviral drug
resistance)
history of and response to antiretroviral therapy
based on clinical response, CD4+ T-cell counts,
viral load measurements, and current disease
stage.
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.
Selection of HIV PEP Regimens
Clin Infect Dis 2004;39:395–401
Determine the exposure code
Yes
Source
material?
No
What type of
exposrues?
No PEP
Small
EC1
Compromised
mucus, or skin
Volume
Intact skin
No PEP
Percutaneous
exposures
Large or long
EC2
Less severe
EC2
Severity
The Sanford Guide to HIV/AIDS Therapy 2010
More severe
EC3
Determine HIV status of exposure
HIV status
of exposure?
HIV -ve
No PEP
Status
unkown
HIV +ve
Low titer
HIV SC1
High titer
HIV SC
unkown
Source
unkown
HIV SC
unkown
HIV SC2
The Sanford Guide to HIV/AIDS Therapy 2010
Determine PEP Recommendation
EC
HIV SC
Recommendation
1
1
Consider basic
regimens
1
2
Basic regimens
2
1
Basic regimens
2
2
Expanded regimens
3
1 or 2
Expanded regimens
1, 2, 3
Unkown
If exposure setting
suggests risks of HIV
exposure, consider
basic regimens
The Sanford Guide to HIV/AIDS Therapy 2010
HIV-positive, class 1 — asymptomatic HIV infection or known low viral load (e.g., <1,500 ribonucleic acid copies/mL).
HIV-positive, class 2 — symptomatic HIV infection, acquired immunodeficiency syndrome, acute seroconversion, or known high
viral load.
¶ For
example, solid needle or superficial injury.
§§ For
example, large-bore hollow needle, deep puncture, visible blood on device, or needle used in patient’s artery or vein.
** For example, a few drops.
¶¶ For example, a major blood splash.
Toxicity
Drug interactions
Drug resistance
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hitherto undiagnosed; in this case, prevalence of
resistance to any class of drug can be estimated as
5–10%;
already diagnosed, and untreated; these patients are
increasingly likely to have had a resistance test
undertaken, since baseline testing is recommended;
on treatment with undetectable viral load; they will be
of very low infectivity, and will also probably have
had a baseline resistance test;
on treatment with detectable viral load; they are likely
to have resistant virus and also a recent resistance
test.
Pregnancy
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Urgent pregnancy testing should be arranged for any female
worker who cannot rule out the possibility of pregnancy
should be counselled about the risks of HIV infection, about
the risks for transmission to her baby, and about what is
known and not known about the potential benefits and risks
of antiretroviral therapy for her and her baby
drugs that may cause nausea may exacerbate pregnancy
associated nausea
Efavirenz is contraindicated in pregnancy and not
recommended for inclusion in PEP regimens
Indinavir (IDV) is associated with infrequent side effects in
adults (i.e., hyperbilirubinemia and renal stones) that could
be problematic for a newborn.
Follow-up
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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.
Am J Med. 1997 May 19;102(5B):115-6.
員工污染性尖銳器械傷害後感染追蹤檢驗流程
發生被感染病人使用過之物品扎傷或割傷等情況
病人為
HBsAg(+)
病人為
anti-HIV(+)
員工檢驗
anti-HIV，
視情況服用
抗愛滋藥物
員工本人為
HBsAg(+)或
anti-HBs(+)或
anti-HBc(+)
扎傷後一、
三、六個月
、一年追蹤
anti-HIV
不需注射
疫苗或HBIG
員工為HBsAg(-)、
anti-HBs(-) 且未注射
疫苗; 員工本人為
HBsAg(-)、antiHBs(-)已完成注射但
未產生抗體
儘快注射HBIG
並接種疫苗
病人為
anti-HCV(+)
病人為
VDRL(+)
TPHA1:80
員工抽血檢驗
anti-HCV
Penicillin
預防注射
員工為
anti-HCV()
扎傷後半年、一
年抽血檢驗antiHCV, GOT, GPT
扎傷後半年、一年追蹤GOT, GPT, HBsAg, anti-HBs, anti-HBc 等
Clin Infect Dis
1999;28:365–83
Occupational HIV infection

The majority of documented infections occurred in
nurses or clinical laboratory workers (66 of 94;
70.2%) after contact with infected blood (84 of 94;
89.4%) from a patient with with infected blood (84
of 94; 89.4%) from a patient with AIDS (40 of 52;
76.5%), by percutaneous exposure (83 of 94;
88.3%) during a procedure involving the
placement of a device in an artery or vein (43 of
63; 68%).
Clin Infect Dis 1999;28:365–83
Occupational HIV infection
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Some job categories for which a high exposure
risk has been demonstrated, such as midwives
and surgeons.
Eighteen cases of documented HIV infection
occurred despite PEP with zidovudine.
Four of these patients had a negative HIV test at 6
months following exposure.
However, testing the HCW again at 1 year postexposure can be considered for additional
reassurance.
Clin Infect Dis 1999;28:365–83
Standard Precautions to Prevent HIV
Transmission
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Standard precautions (body substance
isolation plus universal precautions)
 core elements:
○ hand washing
○ barrier precautions
 barrier precautions to prevent direct contact with all
body fluids, except sweat, and tissues
○ minimal manual manipulation of sharp
instruments and devices
○ disposal of these items in puncture-resistant
containers
Other Measures to Prevent HIV
Transmission
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Personal protective barriers
 gloves; gowns; goggles
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Safety devices
 blunt-tip suture needle
 needleless systems
Work techniques
 Sterilization and disinfection
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References
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Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to
HIV and Recommendations for Postexposure Prophylaxis MMWRSeptember 30, 2005 / Vol. 54 / No.
RR-9
HIV post-exposure prophylaxis: Guidance from the UK Chief Medical Officers’ Expert Advisory Group
on AIDS, Sep, 2008, Department of Health, UK
Tsai CC, Follis KE, Sabo A, Beck TW, Grant RF, Bischofberger N, Benveniste RE, Black R.
Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine. Science.
1995 Nov 17;270(5239):1197-9.
Bassett IV, Freedberg KA, Walensky RP. Two drugs or three? Balancing efficacy, toxicity, and
resistance in postexposure prophylaxis for occupational exposure to HIV. Clin Infect Dis. 2004 Aug
1;39(3):395-401. Epub 2004 Jul 16.
Raphael J. Landovitz, and Judith S. Currier. Postexposure Prophylaxis for HIV Infection. N Engl J Med
2009;361:1768-75.
Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, Heptonstall J, Ippolito G,
Lot F, McKibben PS, Bell DM. A case-control study of HIV seroconversion in health care workers after
percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group.
N Engl J Med. 1997 Nov 20;337(21):1485-90.
Giuseppe Ippolito, Vincenzo Puro, Julia Heptonstall, Janine Jagger, Gabriella De Carli, and Nicola
Petrosillo. Occupational Human Immunodeficiency Virus Infection in Health Care Workers: Worldwide
Cases Through September 1997. Clinical Infectious Diseases 1999;28:365–83.
Initiation of Antiretroviral Therapy
CD4 count < 350 cells/mm3
 Pregnancy, HIV-associated
nephropathy, and hepatitis B virus
(HBV) coinfection when treatment of
HBV is indicated.
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Preferred regimens
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Efavirenz/tenofovir/emtricitabine;
ritonavir-boosted atazanavir +
tenofovir/emtricitabine;
ritonavir-boosted darunavir +
tenofovir/emtricitabine; and
raltegravir + tenofovir/emtricitabine.
Lopinavir/ritonavir-based regimens are now listed
as “Alternative” instead of “Preferred” regimens,
except in pregnant women, where twice-daily
lopinavir/ritonavir + zidovudine/lamivudine
remains a “Preferred” regimen.
PLASMA HIV RNA TESTING
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The minimal change in viral load considered to be
statistically significant (2 standard deviations) is a
threefold, or a 0.5 log10 copies/mL change.
One key goal of therapy is suppression of viral
load to below the limits of detection (below 40–75
copies/mL by most commercially available
assays).
For most individuals who are adherent to their
antiretroviral regimens and who do not harbor
resistance mutations to the prescribed drugs, viral
suppression is generally achieved in 12–24
weeks, even though it may take a longer time in
some patients.
CD4+ T-CELL COUNT
increase in CD4 count in the range of
50–150 cells/mm3 per year, generally
with an accelerated response in the first
3 months.
 increase of approximately 50–100
cells/mm3 per year.
 Severely depleted CD4 count may have
a blunted increase in their count despite
virologic suppression.
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Drug resistance testing

Genotypic testing is recommended as the
preferred resistance testing to guide therapy in
patients with suboptimal virologic responses or
virologic failure while on first or second regimens
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Addition of phenotypic testing to genotypic testing
is generally preferred for persons with known or
suspected complex drug resistance mutation
patterns, particularly to protease inhibitors