Updated U.S. Public Health Service Guidelines for the

Management of Occupational Exposures to HBV, HCV, and HIV

and Recommendations for Postexposure Prophylaxis

CDC. MMWR 2001;50(RR-11) http://www.cdc.gov/mmwr/PDF/rr/rr5011.pdf

Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Human

Immunodeficiency Virus (HIV)

• Bloodborne viruses

• Can produce chronic infection

• Transmissible in healthcare settings

• Data from multiple sources (e.g., surveillance, observational studies, serosurveys) used to assess risk of occupational transmission

Preventing Transmissionof Bloodborne Virusesin Healthcare Settings

• Promote hepatitis B vaccination• Treat all patients as potentially

infectious• Use barriers to prevent blood/body

fluid contact• Prevent percutaneous injuries

Factors Influencing OccupationalRisk of Bloodborne Virus Infection

• Prevalence of infection among patients

• Risk of infection transmission after a blood exposure

• Nature and frequency of blood exposures

Prevalence of Bloodborne Virus Infection in Patients

• Generally higher in hospitalized patients than general population

• Varies with geographic area

• Varies with patient group

Risk of Bloodborne Virus Transmission after

Occupational Percutaneous Exposure Source

HBVHBeAg +HBeAg -

HCV

HIV

Risk

22.0-30.0%

1.0-6.0%

1.8%

0.3%

Frequency of Percutaneous Injury in Healthcare Personnel

• Based on CDC estimates, 384,325 (95% CI 311,091-463,922) percutaneous injuries are sustained by healthcare personnel in US hospitals annually*

• The number of injuries sustained outside of hospital settings is unknown

• Frequency of percutaneous injury varies by occupational group and healthcare setting

* Panlilio, AL, et. al. Estimate of the Annual Number of Percutaneous Injuries in U.S. Healthcare Workers. 4th Decennial Conference, March 5-9, 2000

National Surveillance System For Healthcare Workers

http://www.cdc.gov/ncidod/hip/SURVEILL/nash.HTM

Exposure Types for Blood/Body Fluid Exposures* Reported to NaSH

June 1995-December 2000 (n=12,678)

* Excluding intact skin exposures and clean needlesticks. Exposures involving more than one site (4% of all exposures) are counted as one exposure according to the highest risk route for bloodborne virus transmission.

Percutaneous

10,378 (82%)Mucous membrane

1817 (14%)

Non-intact skin

352 (3%)Bite

131 (1%)

Device Types for Percutaneous Injuries Reported to NaSH

June 1995-December 2000 (n=10,378)

Hollow-bore needle (60%)

Solid sharp (32%)

Suture needle (17%)

Scalpel (7%)

Other (8%)

Glass (2%) Other/ unknown (6%)

Hypodermic needle

29%

Winged steel needle

12%

IV stylet Phlebotomy needle * Other hollow-bore needle6% 3% 10%

* Vacuum tube collection/holder/needle

Reasons for Updating the PHS Guideline

• New antiretroviral drugs

• Emerging HIV drug resistance

• Overuse of PEP for low or no risk exposures

• HBV, HCV, and HIV issues best presented in a single document

Elements of an Effective Postexposure Management Program

• Clear policies/procedures

• Training of healthcare personnel (HCP)

• Rapid access to– clinical care– postexposure prophylaxis (PEP)– testing of source patients/HCP

• Injury prevention assessment

Elements of Postexposure Management

• Wound management• Exposure reporting• Assessment of infection risk

– type and severity of exposure– bloodborne infection status of source

person• Appropriate treatment, follow-up, and

counseling

Postexposure Management:Wound Care

• Clean wounds with soap and water• Flush mucous membranes with water• No evidence of benefit for:

– application of antiseptics or disinfectants– squeezing (“milking”) puncture sites

• Avoid use of bleach and other agents caustic to skin

Postexposure Management:The Exposure Report

• Date and time of exposure• Procedure details…what, where, how, with

what device• Exposure details...route, body substance

involved, volume/duration of contact• Information about source person and

exposed person• Exposure management details

Postexposure Management: Assessment of Infection Risk

• Type of exposure– percutaneous– mucous membrane– non-intact skin– bites resulting in blood

exposure• Body substance

– blood– bloody fluid– potentially infectious

fluid or tissue

• Source person– presence of HBsAg

– presence of HCV antibody

– presence of HIV antibody

– if source unknown, assess epidemiologic and clinical evidence

Postexposure Management: Unknown or Untestable Source

• Consider information about exposure– where and under what circumstances – prevalence of HBV, HCV, or HIV in the

population group• Testing of needles and other sharp instruments

not recommended– unknown reliability and interpretation of findings– hazard of handling sharp instrument

Postexposure Management:Evaluating the Source

• Informed consent should be obtained in accordance with state and local laws

• Confidentiality of the source person

Postexposure Management: Evaluating the Source (cont.)

• If the HBV, HCV, and/or HIV status of the source is unknown, perform testing

• Perform testing as soon as possible

• Consult laboratory regarding most appropriate test to expedite obtaining results

Postexposure Management: Evaluating the Source for HBV

• Presence of hepatitis B surface antigen (HBsAg) indicates source is infected with HBV

Postexposure Management: Evaluating the Source for HCV

• Repeatedly reactive results by EIA for anti-HCV should be confirmed by supplemental test (RIBA or HCV PCR)

• Direct virus assays not recommended

Postexposure Management: Evaluating the Source for HIV

• EIA

– Consider rapid test if EIA testing cannot be completed within 24-48 hours

• Confirmation of reactive result not necessary for PEP management

• Direct virus assays (e.g., PCR, p24 antigen) not recommended

Occupational HBV Exposures

Estimated Incidence of HBV infections among HCP and General Population,

United States, 1985-1999

0

50

100

150

200

250

300

350

1985 1987 1989 1991 1993 1995 1997 1999

Year

Inci

den

ce p

er 1

00,0

00

Healthcare Personnel

General U.S. Population

Hepatitis B Vaccination Coverage of HCP in 113 US Hospitals, 1994-1995*

Occupation Phlebotomist/technician Radiologist/therapist Nurse Physician/resident Nurse aide Maintenance/security Clerical Food service Total

No.Eligible

149 1961,056 61 645 132 222 692,530

Received3 Doses, %

81 73 72 71 63 59 44 44

66.5

*Arch Intern Med 1997;157:2601

Concentration of HBV in Body Fluids

High Moderate Low/Not Detectable

Blood Semen Urine Serum Vaginal Fluid Feces Wound exudates Saliva Sweat

Tears Breast Milk

Elements of Postexposure Management: HBV

• Baseline evaluation and testing of exposed person with unknown HBV immune status

• Consideration of treatment

– when to give

– what to give

• Follow-up testing and counseling

Postexposure Management: Baseline HBV Testing of Exposed* Person

• Test for anti-HBs if person has been vaccinated, but vaccine response is unknown

• Baseline testing not necessary if exposed person has not been vaccinated or vaccine response is known

* Source HBsAg positive or status unknown

Vaccination and antibody status of exposed person

Unvaccinated

Previously vaccinated Known responder

Known nonresponder

Antibody response unknown

Treatment when source is HBsAg positive

HBIG x 1 and initiate hepatitis B vaccine series

No treatment

HBIG x 1and initiate re-vaccination or

HBIG x 2

Test exposed person for anti-HBs1. If adequate, no treatment2. If inadequate, HBIG x 1 and vaccine booster

Recommended Postexposure Management: PEP for Exposure to HBV

Vaccination and antibody status of exposed person

Unvaccinated

Previously vaccinated Known responder

Known nonresponder

Antibody response unknown

Treatment when source is not

tested or status unknown

Initiate hepatitis B vaccine series

No treatment

If known high-risk source treat as if source were HBsAg positive

Test exposed person for anti-HBs1. If adequate, no treatment2. If inadequate, vaccine booster

and recheck titer in 1-2 mos

Recommended Postexposure Management: PEP for Exposure to HBV

Side Effects of Hepatitis B Vaccine

• Pain at injection site

• Mild to moderate fever

• Anaphylaxis in an estimated 1 in 600,000 doses given

• No serious adverse events detected through surveillance

• No risk of adverse effects to fetus

Efficacy of HBV PEP*

Regimen

Multiple doses of HBIG alone when 1st dose initiated within 1 week

Hepatitis B vaccine series alone

Combination of HBIG and vaccine series

Prevention of HBV Infection

70-75%

70-75%

85-95%

* Estimated for adults, based on perinatal data

Hepatitis B Vaccine: Long-Term Efficacy

• Anti-HBs titers decline to <10 mIU/mL in 30-50% of adults within 8-10 years after vaccination

• Exposure to HBV results in anamnestic anti-HBs response that prevents clinically significant HBV infection

• Immune memory remains intact for at least 20 years after immunization

• Chronic HBV infection rarely documented among vaccine responders

• Booster doses currently not recommended

Postexposure Management: Follow-up HBV Testing of Exposed Person

• Perform follow-up anti-HBs testing in healthcare personnel who receive hepatitis B vaccine– test for anti-HBs 1-2 months after last dose– anti-HBs response to vaccine cannot be

ascertained if HBIG received in the previous 3-4 months

Postexposure Management:HBV Postexposure Counseling

• Refrain from donating blood, plasma, organs, tissue, or semen.

• No need for:– modification of sexual practices or refraining from

becoming pregnant– special precautions to prevent secondary transmission.– modification to patient care responsibilities for exposed

person

• If acute HBV infection, evaluate according to published recommendations

Occupational HCV Exposures

Occupational Transmission of HCV

• Inefficiently transmitted by occupational exposures

• Average incidence 1.8% (range 0-7%) following percutaneous exposure from HCV-positive source

• Case reports of transmission from blood splash to mucous membrane

• Prevalence 1-2% among healthcare personnel – Lower than among adults in the general population– 10 times lower than for HBV infection

Elements of Postexposure Management: HCV

• Baseline evaluation and testing

• Follow-up testing and counseling

Postexposure Management:Baseline HCV Testing of Exposed Person

• If HCV-positive source, test exposed person for

anti-HCV and ALT

• If source not infected, baseline testing not

necessary

Postexposure Prophylaxis for HCV

• Not recommended after exposure– immunoglobulin not effective– no data on use of antivirals (e.g., interferon), and

may be effective only with established infection– antivirals not FDA approved for this setting

Postexposure Management:Follow-up of HCV-Exposed HCP

• Test for anti-HCV and ALT 4-6 months after exposure• Test for HCV-RNA at 4-6 weeks for earlier diagnosis

of HCV infection.• Confirm anti-HCV EIA-positive results with

supplemental test (e.g., RIBA)• No guidelines for therapy during acute infection

– when HCV infection identified early, refer worker to a specialist for proper management

Postexposure Management:HCV Postexposure Counseling

• Refrain from donating blood, plasma, organs, tissue, or semen.

• No need for:– modification of sexual practices or refraining from

becoming pregnant– special precautions to prevent secondary

transmission.– modification to patient care responsibilities for

exposed person, even if HCV infected

Occupational HIV Exposures

U.S. Healthcare Personnel with Documented and Possible Occupationally Acquired

AIDS/HIV Infection, by Occupation, June 2001* Documented Possible

Occupation Transmission (No.) Transmission ( No.)

Dental worker, including dentist ---- 6

Embalmer/morgue technician 1 2

Emergency medical technician/paramedic ---- 12Health aide/attendant 1 15Housekeeper/maintenance worker 2 13

Laboratory technician, clinical 16 17

Laboratory technician, nonclinical 3 ---- Nurse 24 34Physician, nonsurgical 6 12Physician , surgical ---- 6Respiratory therapist 1 2Technician, dialysis 1 3Technician, surgical 2 2Technician/therapist, other than above ---- 9Other healthcare occupations ---- 4 Total 57 137

* http://www.cdc.gov/hiv/pubs/facts.htm#Transmission

Exposures Resulting in Occupational HIV Transmission*

June 2001

Percutaneous 48

Mucocutaneous 5

Both 2

Unknown 2

* http://www.cdc.gov/hiv/pubs/facts.htm#Transmission

Sharp Objects Associated with 51 Percutaneous Injuries Resulting in HIV

Seroconversion in 50 Healthcare Personnel*June 2001

Scalpel 2

Hollow-boreneedle 45

Broken vial 2

Unknown 2

* http://www.cdc.gov/hiv/pubs/facts.htm#Transmission

Average Risk of HIV Infection to Healthcare Personnel by Exposure Route

• Percutaneous 0.3%

• Mucous membrane 0.09%

• Non-intact skin <0.1%

Risk Factors for HIV Transmission After Percutaneous Exposure to HIV-Infected Blood:

CDC Case-Control Study*

Risk Factor Adjusted OR ratio (95% CI)

Deep injury 15 (6.0-41)Visible blood on device 6.2 (2.2-21)Procedure involving needle4.3 (1.7-12) placed in artery or veinTerminal illness in source patient 5.6 (2.0-16)Postexposure use of zidovudine 0.19 (0.06-0.52)

*Cardo et al., New Engl J Med 1997;337:1485-90.

• Biological plausibility• Indirect scientific evidence of efficacy

– animal models– human studies

• Safety• Feasibility

Criteria to Establish HIV PEP as a Standard of Care

Animal Studies of PEP Efficacy

• Data have been difficult to interpret and extrapolate to humans, but provide encouraging evidence of PEP efficacy

• Different virus strains, route of inoculation, dose of inocula, and drug regimens used

• Delaying time to PEP, shortening the duration, or decreasing the dose reduced effectiveness of PEP

Human Studies of HIV PEP Efficacy

• Little information on efficacy of PEP in humans• Seroconversion infrequent following occupational

exposure to HIV-infected blood• Use of zidovudine (ZDV) was associated with an

81% decrease in the risk for HIV infection– limitations include a small number of cases, and

that cases and controls came from different cohorts (Cardo et al, NEJM 1997;337:1485-90.)

Human Studies of HIV PEP: Prevention of Perinatal Transmission

• ZDV administered during pregnancy, labor, and delivery reduced transmission by 67%

(Connor EM, et al. N Engl J Med 1994;331:1173-80.)

• Protective effect only partially explained by reduction in maternal viral load

• Protective effect observed when ZDV given only to newborn within the first 48-72 hours of life

(Wade NA, et al. N Engl J Med 1998;339:1409-14.) ( Musoke P, et al. AIDS

1999;13:479-86.) (Guay LA, et al. Lancet 1999;354:795-802.)

HIV PEP:Failures in Healthcare Personnel*

World-wide Cases• 16 cases of ZDV failure

in healthcare personnel• 5 cases of combination

HIV PEP failure • no delay in time to

seroconversion• no adverse effects on

natural history

Potential Explanations• delay in treatment• dose too low / low drug

levels• resistant virus• high inoculum exposure• treatment duration too

short

*Beltrami EM. Semin Infect Control 2001;1:2-18

Reported Failures of Combination HIV PEP*

Source on Injury Regimen Antiretroviral?Biopsy needle ZDV, ddI yesHollow needle ZDV, ddI noLarge-bore hollow needle 3 drugs yes (not resistant)Hollow needle ZDV, 3TC, yes (resistant)

ddI, IDVUnknown sharp ddI, d4T, NVP yes (resistant)

All HCP seroconverted within 100 days

*Beltrami EM. Semin Infect Control 2001;1:2-18

Elements of Postexposure Management: HIV

• Baseline evaluation and testing of exposed person

• Consideration of treatment

– when to give

– what to give

– pregnancy in exposed

• Follow-up testing and counseling

Postexposure Management:Baseline HIV Testing of Exposed Person

• EIA standard test

• Direct virus assays not recommended

– p24 antigen

– PCR for HIV RNA

Initiation of HIV PEP

• If indicated, start PEP as soon as possible after exposure– regard as an urgent medical concern– hours rather than days

• Interval after which PEP is no longer likely to be effective in humans is unknown– initiating PEP days or weeks after an

exposure might be considered if warranted for increased risk exposure

Re-evaluation of HIV-Exposed Person

Consider re-evaluation of the exposed person within 72 hours–additional information about the source

person may become available–if the source person has a negative HIV

antibody test, stop PEP

Important Concepts about HIV PEP

• Determining which and how many agents to use for PEP is largely empiric

• Professional judgement should be used based on local knowledge and experience in treating HIV

• Regimens should be tolerable to the exposed person

Risk of Adverse EffectsRisk of Transmission

Considerations When Using PEP

PEP

Postexposure Management: HIV PEP Basic Regimen

Basic RegimenZidovudine (ZDV): 200 mg tid (300 mg PO bid)Lamivudine (3TC): 150 mg bid

Alternate Basic Regimens Didanosine (ddI): 200 mg bid (125 mg bid if <60 kg) Stavudine (d4T): 40 mg bid (30 mg bid if <60 kg)

Stavudine (d4T): 40 mg bid (30 mg bid if <60 kg) Lamivudine (3TC): 150 mg bid

Postexposure Management: HIV Expanded Regimen

Expanded Regimen

Basic regimen plus one of the following:

Indinavir (IDV): 800 mg q8h Nelfinavir (NFV): 750 mg tid or 1250 mg bidEfavirenz (EFV): 600 mg dailyAbacavir (ABC): 300 mg bid

Recommended HIV PEP for Percutaneous Injuries

Exposure Type

Less Severe

More Severe

HIV positive,class 1

Recommendbasic PEP

Recommendexpanded PEP

HIV positive,class 2

Recommendexpanded PEP

Recommendexpanded PEP

HIV statusunknown

Generally, no PEP

Generally, no PEP

Infection Status of Source

Class 1: Asymptomatic or known low viral load Class 2: Symptomatic, AIDS, or known high viral load

ExposureType

Small Volume(e.g., few drops)

Large Volume(e.g., major blood splash)

HIV positive,class 1

Considerbasic PEP

Recommendbasic PEP

HIV positive,class 2

Recommendbasic PEP

Recommendexpanded PEP

HIV statusunknown

Generally, no PEP

Generally, no PEP

Infection Status of Source

Class 1: Asymptomatic or known low viral load Class 2: Symptomatic, AIDS, or known high viral load

Recommended HIV PEP for Mucous Membrane and Non-Intact Skin Exposures

Situations Where PEP is Rarely, if Ever, Warranted

• Intact skin contact with blood and potentially infectious body fluids

• Exposure to unknown source in populations where HIV prevalence is low

• Low-risk exposure to unknown source

Situations for Which Expert Consultation for HIV PEP is Advised

• Resistance of the source virus to antiretroviral agents

• Known or suspected pregnancy in the exposed person

• Toxicity of the initial PEP regimen

Resistance to Antiretroviral Agents: Implications for PEP

• Resistance to antiretroviral drugs reported

• Transmission of resistant virus reported

• Relevance of exposure to resistant virus not understood

• Patients take many drugs; difficult to know to which drug virus is resistant

• Cross-resistance within drug classes

Resistance to Antiretroviral Agents: Implications for PEP (cont.)

• Recommend selection of drugs to which the source person’s virus is unlikely to be resistant

• Testing of the source person’s virus for resistance at the time of exposure is not recommended

EXPERT CONSULTATION IS ADVISED

HIV PEP Considerations in Pregnant Exposed Women

• General principles– pregnancy is not a contraindication for PEP– exposed person should make informed decision about

PEP• Choosing regimen is more complex

– may exacerbate physiologic changes in pregnancy– short/long-term effects on fetus/newborn unknown– most data are on zidovudine– some drugs contraindicated during pregnancy

HIV PEP During Pregnancy

• Efavirenz NOT recommended during pregnancy because of possible teratogenicity

• Cases of fatal lactic acidosis in pregnant women treated with d4T and ddI reported

• Indinavir should not be given shortly before delivery because of hyperbilirubinemia

Primary Toxicities and Side Effects: Basic Regimens

• Zidovudine (ZDV)– Neutropenia, anemia– Nausea, headache, insomnia, muscle pain, and

weakness• Lamivudine (3TC)

– Abdominal pain, nausea, diarrhea, rash – Pancreatitis (rare)

• ZDV/3TC– Toxicity about the same as ZDV alone

Primary Toxicities and Side Effects: Alternate Basic Regimens

• Didanosine (ddI)– Pancreatitis, lactic acidosis, neuropathy– Diarrhea, abdominal pain, nausea

• Stavudine (d4T)– Peripheral neuropathy, pancreatitis, increased

liver function tests, anemia, neutropenia– Headache, diarrhea, nausea, insomnia,

anorexia

Toxicities and Side Effects: Expanded HIV PEP Regimens

• All protease inhibitors– inhibit metabolism of non sedating antihistamines

and other hepatically metabolized drugs– increase diabetes-related problems

• Indinavir– may cause nausea, abdominal pain, nephrolithiasis

• Nelfinavir – accelerates clearance of certain drugs, including oral

contraceptives– may cause diarrhea, nausea, abdominal pain,

weakness, rash

Toxicities and Side Effects: Expanded Regimens (cont.)

• Efavirenz– Rash– Nervous system problems (e.g., dizziness,

insomnia)• Abacavir

– Nausea, diarrhea, anorexia, abdominal pain, fatigue, headache, insomnia

– Hypersensitivity reactions

Reported Cases of Toxicity Associated with Nevirapine for PEP*

• Fulminant liver failure (one requiring liver transplantation) and hypersensitivity reaction have been reported in healthcare personnel taking nevirapine for PEP

• FDA has received 22 reports of serious adverse events related to nevirapine taken for PEP– hepatotoxicity (12 cases)– skin rash (14 cases)– rhabdomyolysis (1 case)

*MMWR 2001;49:1153-1155

Postexposure Management:Follow-up HIV Testing of Exposed Person

• If source HIV positive, test at 6 weeks, 3 months, 6 months – EIA standard test– direct virus assays not recommended

• Extending follow-up to 12 months – recommended for HCP who become infected

with HCV following exposure to co-infected source

– optional in other situations

Postexposure Management:Monitoring for PEP Toxicity

• Tests at baseline and 2 weeks after starting PEP– complete blood count– renal and hepatic profiles

• Follow-up testing if taking protease inhibitor – monitor for hypoglycemia – monitor for crystalluria, hematuria, hemolytic

anemia, and hepatitis if on indinavir• Modify regimen if toxicity noted• Expert consultation encouraged

Postexposure Management: HIV Postexposure Counseling

• Side effects of PEP drugs

• Signs and symptoms of acute HIV infection– fever– rash– flu-like illness

• Prevention of secondary transmission

– sexual abstinence or condom use

– no blood/tissue donation

• Transmission and PEP drug risks if breastfeeding

No work restriction indicated

Summary of Updated Recommendations for HIV

Exposure Management

• Inclusion of new antiretroviral drugs• Stronger statements regarding unnecessary

use of PEP • Use of rapid testing for source patients• Discourage use of direct virus assays for

follow-up• Follow-up evaluation within 72 hours

postexposure

Recommendations for Healthcare Facilities

• Establish a bloodborne pathogen management policy

• Implement management policies (e.g., training, hepatitis B vaccination, exposure reporting, PEP access, etc.)

• Establish laboratory capacity for bloodborne virus testing

• Select and use appropriate PEP regimens

Recommendations for Healthcare Facilities (cont.)

• Provide access to counseling for exposed personnel

• Monitor adverse events and seroconversion• Monitor exposure management programs (e.g.,

time between exposure and evaluation, testing of source persons, completion of follow-up)

Conclusion

• Occupational exposure management is complex

• Prevention is best– hepatitis B immunization– avoiding occupational blood exposures

• Join the Division of Healthcare Quality Promotion in challenge of eliminating needlesticks

Sources of Additional Information

• Division of Healthcare Quality Promotion Phone: 800-893-0485

Homepage: http://www.cdc.gov/ncidod/hip/

• Hepatitis HotlinePhone: 888-443-7232Homepage: http://www.cdc.gov/hepatitis

• Needlestick!Homepage:http://www.needlestick.mednet.ucla.edu

Sources of Additional Information

• National Institute for Occupational Safety and Health bloodborne pathogens website

http://www.cdc.gov/niosh/bbppg.html

• Occupational Safety and Health Administration bloodborne pathogens websitehttp://www.osha-slc.gov/SLTC/bloodbornepathogens/index.html

PEPline• National Clinicians’ Post-Exposure

Prophylaxis Hotline (PEPline)• Free consultation for clinicians treating

occupational exposures to HIV and other bloodborne pathogens…

• 24 hours a day• 7 days a week

• 1-888-HIV-4911• http://www.ucsf.edu/hivcntr/

• a joint program of UCSF/SFGH CPAT / EPI Center supported by HRSA and CDC

PREVENTION IS PRIMARY!

PREVENTION IS PRIMARY!

Protect patients…protect healthcare personnel…

promote quality healthcare!