# Presentation: 068641

## 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

**Notes:**
Hepatitis B virus (HBV), hepatitis C virus (HCV), and the human immunodeficiency virus (HIV) are all bloodborne viruses that can produce chronic infection and are transmissible in healthcare settings. Data from multiple sources, including surveillance, observational studies, and serosurveys are used to assess the risk of occupational transmission. 

## Preventing Transmissionof Bloodborne Virusesin Healthcare Settings

- Promote hepatitis B vaccination
- Treat all patients as potentially infectious
- Use barriers to prevent blood/body fluid contact
- Prevent percutaneous injuries

**Notes:**
Preventing transmission of bloodborne viruses in healthcare settings requires a multifaceted approach, including promoting hepatitis B vaccination of all healthcare personnel who may have contact with blood, considering all patients as potentially infectious, using appropriate barriers to prevent blood and body fluid contact, and preventing percutaneous injuries, by eliminating unnecessary needle use, implementing safety devices (devices with safety features), using safe work practices when handling needles and other sharp devices,  and safely disposing sharps and blood-contaminated materials.

## Factors Influencing Occupational

**Risk of Bloodborne Virus Infection**

- Prevalence of infection among patients
- Risk of infection transmission after a blood exposure
- Nature and frequency of blood exposures

**Notes:**
Three major factors influence the occupational risk of bloodborne infection. These factors  must all be considered  to fully understand the risk to healthcare personnel. First, if the patient population has a high prevalence of bloodborne infection, the risk to healthcare personnel is higher. Second, the risk of infection transmission after a blood exposure varies by type of exposure and the virus to which exposure occurs. Lastly, healthcare personnel who are frequently exposed to blood, especially if they work with sharp objects such as needles, have a higher risk of exposure to a bloodborne viruses than those rarely coming in contact with blood. In the next few slides, we will discuss each of these factors.

## Prevalence of Bloodborne Virus Infection in Patients

- Generally higher in hospitalized patients than general population
- Varies with geographic area
- Varies with patient group

**Notes:**
The prevalence of bloodborne virus infection varies. It is generally higher in hospitalized patients than in the general population, but also varies with geographic area and patient group. For example, in Iowa, the prevalence of HIV may be lower than in San Francisco. The prevalence varies with patient group and the presence or absence of such risk factors as injecting drug use, multiple sex partners, and so on.

## Risk of Bloodborne Virus Transmission after Occupational Percutaneous Exposure

-   _Source_
- 	HBV
- 		HBeAg +
- 		HBeAg -
- 	HCV
- 	HIV

- _ __Risk_
- 22.0-30.0%
- 1.0-6.0%
- 1.8%
- 0.3%

**Notes:**
The risk of HBV transmission after a percutaneous exposure to HBV-infected blood, without postexposure treatment, varies, depending on the e-antigen status of the source. If the source is e-antigen positive, the risk of transmission will be up to 30%, whereas if the source is e-antigen negative, the risk is from 1-6%. The average risk of HCV transmission after a percutaneous exposure to HCV-infected blood is 1.8%, with a range of 0-7%. The average risk of HIV infection after a percutaneous exposure to HIV-infected blood is 0.3%, or 1 in 300 exposures (with a 95% confidence interval of 0.2%-0.5%). The average risk is based on aggregate data, and may not apply to specific exposure events.

## 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

**Notes:**
The third factor influencing the occupational risk of bloodborne infection is the nature and frequency of blood exposure. Based on CDC estimates, approximately 384,325 percutaneous injuries (i.e., approximately 1,000 a day) are sustained by healthcare personnel in US hospitals annually. The number of injuries sustained outside of hospital settings is unknown.  The frequency of exposure to blood due to a percutaneous injury varies by occupational group and healthcare setting.

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

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

**Notes:**
We can also use surveillance data to look at the nature of exposures. One system is CDC’s National Surveillance System for Healthcare Workers, or NaSH. NaSH is a multi-component surveillance system that collects information about exposures to blood and bloodborne viruses. We can use NaSH data to look at the nature of exposures reported in NaSH hospitals. NaSH data presented in the following slides are from 49 NaSH facilities, for the time period from June 1995 through December 2000.

## 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%)**

**Notes:**
This pie chart shows the types of exposures to blood and body fluids reported to NaSH between June 1995 and December 2000. There were 12,678 exposures reported, with percutaneous exposures accounting for 82% followed by mucous membrane exposures, non-intact skin, and bites. Contacts with intact skin and clean needlesticks are excluded, because they are not considered exposures. 

## 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 needle**

**6%**

**3%**

**10%**

*** Vacuum tube collection/holder/needle**

**Notes:**
This chart shows the distribution of devices involved in the percutaneous injuries reported to NaSH from June 1995 through December 2000.  Many different devices were associated with the 10,378 injuries reported during that period.  The most commonly implicated devices were hollow-bore needles, shown in blue, and accounting for 60% of  percutaneous injuries.

## 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

**Notes:**
There were several reasons for updating the PHS guideline. One reason was to include discussion of new antiretroviral drugs approved since the publication of the guideline in 1998 as well as new combinations of drugs to consider.  There are increasing concerns about HIV drug resistance as fewer patients are treatment naïve.  There are indications of overuse of PEP for low or no risk exposures. Finally, it made sense to create a single document addressing occupational exposures to HIV, HBV, and HCV. 

## 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

**Notes:**
Avoiding occupational blood exposure is the primary way to prevent transmission of HBV, HCV, and HIV. However, postexposure management is an integral component of a complete program to prevent infection following bloodborne virus exposure. Elements of an effective postexposure management program include policies and procedures that address confidentiality of exposed and source persons; clearly state how to manage exposures; are known to managers and those potentially at risk; and are posted in a visible place.  Education and training of healthcare personnel are essential to alleviate misconceptions and fears.  Additionally, resources should be available for rapid access to clinical care, postexposure prophylaxis, and testing of both source patients and exposed healthcare personnel. Injury prevention assessment is also crucial, as each injury provides an opportunity to learn how to prevent injuries.  

## 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

**Notes:**
The key elements of postexposure management are listed here. Over the next few slides, wound management, exposure reporting, assessment of the infection risk by type and severity of exposure,  determination of the bloodborne status of the source person, and appropriate treatment, follow-up, and counseling are explored in more detail. 

## 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

**Notes:**
The first element in postexposure management is wound care.  Wounds should be cleaned with soap and water. Mucous membranes should be flushed with water. Eyes should be flushed with eye irrigant or clean water. There is no evidence that application of antiseptics or disinfectants, or squeezing (or milking) puncture sites provides any benefit.  The use of bleach and other agents that are caustic to the skin should be avoided. 

## 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

**Notes:**
It is important to collect and record information about the exposure on an exposure report, and to maintain the confidentiality of both the worker and the source patient.  An exposure report should include the date and time that the exposure occurred, as well as details of what procedure was being performed, where, how, and what device (if any) was involved.  If a device was involved, OSHA requires that the brand and manufacturer of the device be recorded. Details such as the route of exposure, body substance involved, and volume or duration of contact also should be included. Additionally, information about the source person and exposed person, if known, is critical, along with exposure management details, which will be discussed later.

## 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

**Notes:**
To assess the risk of infection, first consider the type of exposure. Those that pose a risk of infection are percutaneous injuries, mucous membrane exposures, exposures to non-intact skin, and bites resulting in blood exposure. In general, percutaneous injuries pose a greater risk than mucous membrane and non-intact skin exposures.  The next thing to consider is the body substance involved in the exposure. Although blood and bloody fluid exposures are the most risky, there are other potentially infectious fluids or tissues, such as semen, vaginal secretions, cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluid.  Finally, the infection status of the source of the exposure must be evaluated. If the source is known but infection status unknown, HBV, HCV, and HIV testing should be performed.  However, if the source is unknown, information on the type of exposure, and body substance, along with any other pertinent information must be considered before deciding postexposure management.

## 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

**Notes:**
If the source is unknown, or cannot be tested, information about where and under what circumstances the exposure occurred should be assessed clinically and epidemiologically for the likelihood of transmission of HBV, HCV, or HIV. Certain situations as well as the type of exposure might suggest an increased or decreased risk; an important consideration is the prevalence of HBV, HCV, or HIV in the population group (such as an institution or community) from which the contaminated source material is derived. For example, an exposure occurring in a geographic area where injection-drug use is prevalent and involves a needle discarded in a drug-treatment facility would be considered to pose a higher risk for transmission than an exposure occurring in a nursing home for the elderly in the same region. Testing of needles or other sharp instruments implicated in an exposure, regardless of whether the source is known, is not recommended. The reliability and interpretation of findings in such circumstances are unknown, and handling the sharp might be hazardous to personnel. 

##   Postexposure Management:Evaluating the Source 

- Informed consent should be obtained in accordance with state and local laws
- Confidentiality of the source person

**Notes:**
It is important to keep in mind the rights of the source person. Informed consent should be obtained from the source person, in accordance with state and local laws. Confidentiality of the source person should be maintained at all times. 

##   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

**Notes:**
If the HBV, HCV, and/or HIV infection status of the source is unknown, the source person should be informed of the incident and tested for serologic evidence of bloodborne virus infection. Testing to determine the HBV, HCV, and HIV infection status of an exposure source should be performed as soon as possible. The laboratory should be consulted regarding the most appropriate test to use to expedite obtaining these results. 

## Postexposure Management: Evaluating the Source	for HBV

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

**Notes:**
The presence of hepatitis B surface antigen (HBsAg) indicates the 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

**Notes:**
When testing the source for HCV, repeatedly reactive results by enzyme immunoassay (EIA) for anti-HCV should be confirmed by a supplemental test such as recombinant immunoblot assay (RIBA), or HCV polymerase chain reaction (PCR). Direct virus assays are 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

**Notes:**
When evaluating the source for HIV, EIA testing should be performed. Consider using an FDA-approved rapid HIV-antibody test kit, particularly if testing by EIA cannot be completed within 24-48 hours. Confirmation of a reactive result by Western blot or immunofluorescent antibody is not necessary to make initial decisions about postexposure management, but should be done before notifying the source of the result. And, as for HCV, direct virus assays such as PCR and p24 antigen are not recommended.

## Occupational HBV Exposures

## Estimated Incidence of HBV infections among HCP and General Population, United States, 1985-1999

**Healthcare Personnel**

**General**** ****U.S. Population**

**Notes:**
This graph shows a 90% decline in the incidence of HBV infections in healthcare personnel from the year 1985 to 1999. In the early to mid 1980’s, the incidence of HBV infection in healthcare personnel was much higher than in the general population.  However, following the 1987 publication of universal precaution guidelines and the 1991 Occupational Safety and Health Administration requirement that employers provide HBV vaccination to healthcare personnel, the incidence in healthcare personnel has dropped below that in the general 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
-   196
- 1,056
-     61
-   645
-   132
-   222
-     69
**2,530 **

- _Received_
- _3 Doses, %_
-   81
-   73
-   72
-    71
-   63
-   59
-   44
-    44
**      ****66.5**

- *Arch Intern Med 1997;157:2601

**Notes:**
A study was conducted in 1994-95 at 113 randomly selected hospitals throughout the United States of 2,530 healthcare personnel who were eligible for hepatitis B vaccine. Overall, only 66.5% had received all 3 doses of the vaccine, with coverage varying by occupation.  The difference is due at least in part to different risks of exposure, with phlebotomists/technicians having the highest coverage, and food service workers the lowest.   Nevertheless, it is of concern that only a little more than 70% of nurses and doctors were vaccinated for hepatitis B.  Of the 30% that were not vaccinated, undoubtedly a large proportion were susceptible to HBV infection.

## 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

**Notes:**
As mentioned earlier, one factor to consider in assessing the risk of infection is the body substance to which healthcare personnel are exposed. This shows the concentration of HBV in various body fluids. On the left, in red, are the fluids with the highest concentration of virus. Moving from the left to the right side, the concentration decreases. Blood, for instance, has a higher virus concentration than urine or sweat. 

## 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

**Notes:**
General elements of postexposure management for bloodborne viruses have been discussed.  The following slides address the management of specific exposures, first to HBV. The first element is baseline evaluation and testing of the exposed person. The second is treatment considerations, including when it is appropriate to give treatment, and what to give. The last element is 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

**Notes:**
If the exposed person has been vaccinated, but his/her antibody response is unknown, baseline testing for anti-HBs needs to be done. However, if the source is not infected, or the exposed person is either a known responder or nonresponder, then baseline testing for HBV is not necessary. 

## 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 ****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-HBs
- 1.  If adequate, no treatment
- If inadequate, HBIG x 1
-       and  vaccine booster

** **
** **

**Recommended Postexposure Management: ****PEP for Exposure to HBV**

**Notes:**
For exposures to HBV, the HBsAg status of the source (in pink) and the hepatitis B vaccination and vaccine-response status of the exposed worker (in green) have to be considered for PEP. Vaccination should be initiated for any unvaccinated personnel exposed to blood or body fluids. When HBIG is indicated, it should also be administered as soon as possible after exposure, and may be administered simultaneously with hepatitis B vaccine at a separate site.  No PEP is necessary for personnel who are known responder to the vaccine. Exposed personnel who are known NOT to have responded to a primary vaccine series should receive a single dose of HBIG and the first dose of a second hepatitis B vaccine series as soon as possible after exposure. The same approach is recommended for personnel who did not respond to a 3-dose vaccine series and have not completed a second 3-dose vaccine series. For personnel who failed to respond a second vaccine series, 2 doses of HIBG should be administered (first dose after exposure and second dose 1 month later). Exposed personnel who have an unknown antibody response should be tested for anti-HBs. If the level is adequate, no treatment is necessary. If the level is inadequate, a single dose of HBIG, along with a vaccine booster should be administered.

## 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-HBs
- 1.  If adequate, no treatment
- 2.  If inadequate, vaccine  booster and recheck  titer in 1-2 mos

**Recommended Postexposure Management: ****PEP for Exposure to HBV**

**Notes:**
As mentioned previously, all unvaccinated personnel exposed to blood or body fluid should initiate the hepatitis B vaccine series, regardless of the status of the source. Persons with a high risk exposure to HBV (from an untested or unknown source) who are known not to have responded to a primary vaccine series should be treated as if the source were HBsAg positive, and should receive a single dose of HBIG and the first dose of a second hepatitis B vaccine series as soon as possible after exposure. This option is preferred for vaccine nonresponders who did not complete a second 3-dose vaccine series. Alternatively, persons who previously completed a second vaccine series but failed to respond should receive two doses of HBIG, one dose as soon as possible after exposure, and the second dose 1 month later. Persons exposed to HBsAg-positive blood or body fluids who have an unknown antibody response should be tested for anti-HBs. If the level is adequate, no treatment is necessary. If the level is inadequate, a single dose of HBIG, along with a vaccine booster should be administered. After the appropriate prophylaxis is determined, the next consideration is follow-up testing.

## 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

**Notes:**
Side effects of the hepatitis B vaccine are mild and may include pain at the injection site, and mild to moderate fever. Anaphylaxis is seen in an estimated 1 in 600,000 doses given; no other serious adverse events have been detected through surveillance. In addition, since there is no risk of adverse effects to the fetus if hepatitis B vaccine is administered during pregnancy, vaccination is not contraindicated during pregnancy.

## 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

**Notes:**
The efficacy of HBV prophylaxis varies by the regimen used and e antigen status of the source.  In the first column is the prophylaxis regimen, and in the second column is the efficacy of the regimen at preventing HBV infection, based on data from studies of perinatal transmission of HBV where mothers were HBsAg- and HBeAg-positive. Multiple doses of HBIG alone, when initiated within 1 week of exposure, can prevent 70-75% of HBV infection. Similarly, hepatitis B vaccine series alone can prevent 70-75% of HBV infection.  However, it is estimated that the combination of HBIG and the hepatitis B vaccine series can prevent HBV infection in 85-95% of cases.   

## 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**

**Notes:**
Studies of the long-term efficacy of the hepatitis B vaccine have shown that anti-HBs titers decline to <10 mlU/mL in 30-50% of adults within 8-10 years after vaccination. Nevertheless, exposure to HBV results in an anamnestic anti-HBs response that prevents clinically significant HBV infection. Despite the decrease of antibodies, this immune memory remains intact for at least 20 years after hepatitis B immunization, and chronic HBV infection has only rarely been documented among vaccine responders.  Therefore, booster doses of hepatitis B vaccine are 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

**Notes:**
Follow-up anti-HBs testing of the exposed person depends on the postexposure prophylaxis  administered. If only vaccine was given, anti-HBs testing should be done 1-2 months after receipt of the last vaccine dose. If, however, the exposed person is immune to HBV, or received  HBIG in the previous 3-4 months, no follow-up testing is recommended. Nor is follow-up testing necessary if the source is not HBV infected.

## 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

**Notes:**
Healthcare personnel exposed to hepatitis B-infected blood should be counseled about refraining from donating blood, plasma, organs, tissue, or semen during the follow-up period. There is no need to modify sexual practices or refrain from becoming pregnant, or breastfeeding, or for special precautions to prevent secondary transmission.  The healthcare personnel should continue to follow recommended infection control practices, including standard precautions and appropriate use of hand washing, protective barriers, and care in the use and disposal of needles and other sharp instruments. Additionally, there is no need to modify patient care responsibilities for the exposed person. If the healthcare personnel are found to have acute HBV infection, they should be evaluated according to published recommendations for infected healthcare personnel.

##  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

**Notes:**
HCV is inefficiently transmitted by occupational exposures. The average incidence is 1.8% (range 0-7%) following percutaneous exposure from an HCV-positive source. Cases of transmission from blood splash to mucous membranes have been reported, but there have been no reports of transmission from skin exposures to blood. HCV prevalence is 1-2% among healthcare personnel, which is lower than among adults in the general population and 10 times lower than for HBV infection. 

## Elements of Postexposure Management: HCV

- Baseline evaluation and testing
- Follow-up testing and counseling

**Notes:**
Elements of postexposure management for HCV include baseline evaluation and testing of the exposed person, and 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

**Notes:**
Baseline HCV testing, i.e., anti-HCV and ALT, should be done if the source is known to be HCV positive. However, if the source is not HCV infected, this baseline testing is 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

**Notes:**
For HCV, there is no recommended postexposure prophylaxis. Immunoglobulin is not effective, and there are currently no data on the use of antivirals, which may be effective only with established infection, and are 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

**Notes:**
Even though postexposure prophylaxis is not recommended for HCV, follow-up testing should still be performed. If the source is HCV positive, a test for anti-HCV and ALT should be done 4-6 months after exposure. HCV-RNA may be performed at 4-6 weeks if earlier diagnosis of HCV infection is desired. A supplemental anti-HCV test should be performed to confirm the results of the positive testing. There are no guidelines for therapy during an acute HCV infection. When HCV infection is identified early, the worker should be referred 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

**Notes:**
Healthcare personnel exposed to hepatitis C-infected blood should refrain from donating blood, plasma, organs, tissue, or semen during the follow-up period. There is no need to modify sexual practices or refrain from becoming pregnant, or breastfeeding, or for special precautions to prevent secondary transmission.  The healthcare personnel should continue to follow recommended infection-control practices, including standard precautions and appropriate use of hand washing, protective barriers, and care in the use and disposal of needles and other sharp instruments. Additionally, there is no need to modify patient care responsibilities for the exposed person, even if the HCP is found to have HCV infection. 

## 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	  ----			12
- Health aide/attendant   			     1		      	15
- Housekeeper/maintenance worker 		     2	       		13
- Laboratory technician, clinical 			    16	      		17
- Laboratory technician, nonclinical		      3		               ----
- Nurse 					    24			34
- Physician, nonsurgical			      6			12
- Physician , surgical				   ----		  	  6
- Respiratory therapist 			      1		       	  2
- Technician, dialysis				      1		                  3
- Technician, surgical				      2		 	  2
- Technician/therapist, other than above		   ----			  9
- Other healthcare occupations			   ----		  	  4
**Total    ****	****	****	****	****	****     57****	****	****      ****	****137**

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

**Notes:**
This chart shows the number of U.S. healthcare personnel with documented and possible occupationally acquired AIDS/HIV infection reported to CDC, by occupation, as of June 2001. Fifty-seven workers had documented HIV seroconversion temporally associated with an occupational exposure. An additional 137 episodes are considered possible occupational HIV transmissions. These workers report a history of occupational exposure to blood, other infectious body fluids, or laboratory solutions containing HIV, and report no other risk for HIV infection, but HIV seroconversion after a specific exposure was not documented. The occupational group with the most documented and possible transmissions is nurses. 

## Exposures Resulting in Occupational HIV Transmission*

**June 2001**

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

**Notes:**
Forty-eight infected healthcare personnel sustained 49 percutaneous exposures (one worker sustained two percutaneous injuries from HIV-infected patients within a 10-day period). Two other healthcare personnel had concurrent percutaneous and mucocutaneous exposures. Five healthcare personnel had mucocutaneous exposures. Two workers had an unknown route of exposure; one of these handled concentrated HIV.

## Sharp Objects Associated with 51 Percutaneous Injuries Resulting in HIVSeroconversion in 50 Healthcare Personnel*June 2001

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

**Notes:**
For the 50 documented cases of HIV infection associated with the 51 percutaneous injuries from the previous slide, the types of sharp objects implicated are shown on this pie chart. The largest portion of the pie, in red, represents hollow-bore needles. Other sharp objects represented on this chart include scalpels, in peach, and broken vials, in green. The purple slice represents cases where the sharp object causing the injury was unknown.

## Average Risk of HIV Infection to Healthcare Personnel by Exposure Route

- Percutaneous			 0.3%
- Mucous membrane	 	0.09%
- Non-intact skin			<0.1%

**Notes:**
In prospective studies of healthcare personnel, the average risk of HIV transmission after a percutaneous exposure to HIV-infected blood has been estimated to be approximately 0.3% and after a mucous membrane exposure, approximately 0.09%. Although HIV transmission after non-intact skin exposure has 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.

## 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 needle			4.3 (1.7-12)
-   placed in artery or vein
- Terminal 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.

**Notes:**
In a retrospective case-control study of healthcare personnel who had percutaneous exposure to HIV-infected blood, an increased risk for HIV infection was associated with exposure to a larger quantity of blood from the source person as indicated by deep injury, visible blood on the device, or a procedure involving a needle placed in an artery or vein. An increased risk was also associated with exposure to blood from source persons with terminal illness, possibly reflecting either a higher titer of HIV in blood late in the course of AIDS or other factors. Postexposure use of zidovudine was associated with a decreased risk of HIV transmission. 

## Biological  plausibility
Indirect scientific  evidence  of efficacy
 animal models
 human studies
Safety
Feasibility

- Indirect scientific  evidence  of efficacy
-  animal models
-  human studies
- Safety
- Feasibility

**Criteria  to  Establish  HIV PEP as  a Standard of  Care****  **

**Notes:**
Criteria for the establishment of the use of HIV PEP as the standard of care include the biological plausibility that infection can be prevented or ameliorated by using antiretroviral drugs, the indirect scientific evidence of efficacy from animal models and human studies, the safety of using these agents, and the feasibility of providing PEP regimens which are easily accessible, affordable, and well-tolerated. 

## 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

**Notes:**
Animal studies of HIV postexposure prophylaxis have been difficult to interpret and extrapolate to humans, but provide encouraging evidence of postexposure prophylaxis efficacy.  Larger viral inocula decreased prophylactic efficacy, as did delaying time to treatment, shortening the duration, or decreasing the dose of treatment. 

## 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.)***

**Notes:**
There are limited data on the efficacy of HIV postexposure prophylaxis for humans with occupational exposures.  This is difficult to study because the infrequency of seroconversion after occupational exposure would require enrolling large numbers of healthcare personnel.  One source of data on PEP efficacy in humans come from the CDC case-control study, described earlier.   Healthcare personnel from the U.S., France, the UK, and Italy who sustained percutaneous exposures to HIV were compared to healthcare personnel with similar exposures but who did not seroconvert. Use of zidovudine, or ZDV, was associated with an 81% decrease in the risk for HIV transmission. However, this study was limited by the small number of cases, and the fact that cases and controls came from different cohorts. 

## 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.)

**Notes:**
The only other data on HIV postexposure prophylaxis in humans have come from studies of perinatal transmission.   ZDV administered to HIV-infected women during pregnancy, labor, and delivery reduced transmission to infants by 67%. This protective effect was only partially explained by reduction in the maternal viral load. A reduction, though smaller, was also observed when ZDV was given only to the newborn within the first 48-72 hours after birth.

## 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

**Notes:**
However, any protection provided by HIV postexposure prophylaxis is not absolute. Worldwide, there have been 21 documented failures in healthcare personnel. Five of these cases followed use of combination postexposure prophylaxis drug regimens. Despite the failure of postexposure prophylaxis, there was no delay in time to seroconversion, and no adverse effects on natural history. Some potential explanations for these failures include delay in treatment, a prophylaxis dose that was too low, a resistant virus, high inoculum exposure, or a treatment duration that was too short. 

## Reported Failures of Combination HIV PEP*

- 		**Source on**_** **_
**Injury              ****	****Regimen         ****	****Antiretroviral?**
- Biopsy needle	ZDV, ddI	yes
- Hollow needle	ZDV, ddI	no
- Large-bore
-   hollow needle	3 drugs	yes (not resistant)
- Hollow needle	ZDV, 3TC, 	yes (resistant)
- 	ddI, IDV
- Unknown sharp	ddI, d4T, NVP	yes (resistant)

- All HCP seroconverted within 100 days

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

**Notes:**
Shown here are the five reported failures of combination HIV postexposure prophylaxis, which were referenced in the previous slide. The first two failures involved a 2-drug regimen of zidovudine (ZDV) and didanosine (ddI), while the last three involved regimens with three or more drugs. The 3-drug regimens included zidovudine (ZDV), lamivudine (3TC), didanosine (ddI), indinavir (IDV), stavudine (d4T), and nevirapine (NVP). Two of the three failures that involved a 3-plus-drug regimen resulted in transmission of resistant strains of HIV.  All five healthcare personnel started PEP within 2 hours of exposure and all seroconverted within 100 days.

## 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

**Notes:**
Elements of postexposure management for HIV include baseline evaluation and testing of the exposed person; consideration of treatment, including when it is appropriate to give treatment, what to give, and issues of pregnancy in the exposed person; and 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

**Notes:**
For baseline HIV testing of the exposed person, enzyme immunoassay, or EIA, is the standard test. Direct virus assays such as the p24 antigen or polymerase chain reaction (PCR) for HIV RNA are not recommended. 

## 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

**Notes:**
HIV exposures should be regarded as urgent medical concerns, and, if indicated after evaluating the source patient status and type and severity of the injury, postexposure prophylaxis should be initiated as soon as possible after exposure, i.e. within hours rather than days. The interval after which postexposure prophylaxis is no longer likely to be effective in humans is unknown. Initiating postexposure prophylaxis days or weeks after an exposure might be considered if warranted for a higher exposure risk.

## 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

**Notes:**
Re-evaluation of the exposed person should be considered within 72 hours, as additional information about the source person may become available. If the source person has a negative HIV antibody test, postexposure prophylaxis should be stopped.

## 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

**Notes:**
It is important to remember that determining which and how many agents to use for postexposure prophylaxis is largely empiric. Professional judgement should be used when determining postexposure prophylaxis, based on local knowledge and experience in treating HIV. Additionally, the regimen chosen should be tolerable to the exposed person.

## Considerations When Using PEP 

**Risk of Transmission**

**Considerations When Using PEP**

**PEP**

**Notes:**
Ultimately, the decision to use postexposure prophylaxis must balance the risk of transmission against the risk of adverse effects associated with the use of prophylaxis.

## Postexposure Management: HIV PEP Basic Regimen

- _Basic Regimen_
- 	Zidovudine (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

**Notes:**
Most HIV exposures will warrant a two-drug regimen with two nucleoside analogues, as shown on this slide. The standard “basic” regimen consists of 200 milligrams of ZDV taken three times a day (tid) or 300 milligrams taken orally two times a day, in conjunction with 150 milligrams of 3TC taken two times a day (bid).   In addition, two alternate basic regimens also may be considered. 

## 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 bid
- 	Efavirenz (EFV):	600 mg daily
- 	Abacavir (ABC):	300 mg bid

**Notes:**
The addition of a third drug to the two-drug regimen should be considered for exposures that pose an increased risk for transmission. Agents to consider as a third drug include indinavir (800 milligrams taken every 8 hours), nelfinavir, efavirenz, and abacavir.  The choice of drug should take into account the advantages and disadvantages of each drug, including the complexity of the regimen, serious toxicity, and the possibility of drug interaction with other drugs which the exposed person may already be taking.

## Recommended HIV PEP for Percutaneous Injuries

**Exposure Type**
- Less Severe
- More Severe

- HIV positive,
- class 1
- Recommend
- basic PEP
- Recommend
- expanded PEP

- HIV positive,
- class 2
- Recommend
- expanded PEP
- Recommend
- expanded PEP

- HIV status
- unknown
- 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

**Notes:**
The recommended HIV postexposure prophylaxis for a percutaneous injury is based on the infection status of the source and the exposure type. A basic regimen for postexposure prophylaxis is recommended if the source is HIV positive, but asymptomatic or has a known low viral load AND the exposure was less severe (class 1). However, if the exposure was more severe, OR if the source is symptomatic, has AIDS, or has a known high viral load (class 2), regardless of the severity of the exposure, an expanded postexposure prophylaxis regimen is recommended. If the source’s HIV status is unknown, generally no postexposure prophylaxis is warranted, however, a basic 2-drug postexposure prophylaxis regimen could be considered in settings where exposure to HIV-infected persons is likely.

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

**Type**
- Small Volume
- (e.g., few drops)
- Large Volume
- (e.g., major blood splash)

- HIV positive,
- class 1
- Consider
- basic PEP
- Recommend
- basic PEP

- HIV positive,
- class 2
- Recommend
- basic PEP
- Recommend
- expanded PEP

- HIV status
- unknown
- 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**

**Notes:**
The basic regimen of postexposure prophylaxis is recommended for mucous membrane and non-intact skin exposures, regardless of the volume of the exposure, if the source is HIV positive but asymptomatic or has a known low viral load (class 1), OR if the volume of exposure was small AND the source is symptomatic, has AIDS or has a known high viral load (class 2).  However, if the volume of exposure was large AND the source is symptomatic, has AIDS or has a known high viral load (class 2), an expanded postexposure prophylaxis regimen is recommended. Generally, if the source’s HIV status is unknown, regardless of the volume of exposure, no postexposure prophylaxis is warranted.

## 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

**Notes:**
There are some situations where postexposure prophylaxis is rarely if ever warranted, including intact skin contact with  blood and potentially infectious body fluids, exposure to an unknown source in populations where HIV prevalence is low, and a low-risk exposure to an 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

**Notes:**
Expert consultation for HIV postexposure prophylaxis is advised when resistance of the source virus to antiretroviral agents is known or suspected, the exposed person is known or suspected to be pregnant, or the person taking postexposure prophylaxis experiences toxicity on the initial regimen.  Additional details about these situations are provided in the following slides.

## 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

**Notes:**
Resistance to antiretroviral postexposure prophylaxis drugs and transmission of resistant virus has been reported. Nevertheless, despite recent studies and case reports, the relevance of an exposure to a resistant virus is not understood. Because most HIV-infected patients take many drugs, it may be difficult to know to which drug(s) their viruses may be resistant. Resistance occurs with all the available antiretroviral agents, and cross-resistance within drug classes is frequent.

## 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

**Notes:**
It is recommended that drugs be selected 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 the exposure is not recommended because the results will not be available in time to influence the choice of the initial drug regimen. However, in cases where resistance is suspected, 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

**Notes:**
Pregnancy is not a contraindication for postexposure prophylaxis, and therefore, the exposed person should make an informed decision about postexposure prophylaxis. Choosing a regimen is, however, more complex for pregnant exposed women. Some drugs may exacerbate the physiologic changes in pregnancy.  Data are limited on the potential effects of antiretroviral drugs on the developing fetus or neonate. The short- and long-term effects on the fetus or newborn are unknown, and most of the data are for only one drug, zidovudine.  Some postexposure prophylaxis drugs are 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

**Notes:**
Some antiretroviral agents should not be used as postexposure prophylaxis during pregnancy.  Efavirenz is not recommended during pregnancy because of possible teratogenicity. Reports of fatal lactic acidosis in pregnant women treated with the combination of d4T and ddI have prompted warnings about using these drugs during pregnancy.  Indinavir should not be given shortly before delivery because of concerns about possible hyperbilirubinemia in the newborn

## 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

**Notes:**
Persons taking postexposure prophylaxis should be monitored for drug toxicity and side effects. The most commonly encountered side effects are listed in the following slides.  The package inserts include a more complete listing of the reported adverse effects of  the drugs recommended as HIV PEP.  Toxicities of drugs in the basic regimen are shown here.  For ZDV, the side effects are neutropenia, anemia, nausea, headache, insomnia, muscle pain, and weakness. For lamivudine, or 3TC, the side effects are abdominal pain, nausea, diarrhea, rash, and rarely pancreatitis. For the combination of ZDV and 3TC, the toxicity is 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

**Notes:**
Primary toxicities and side effect of drugs in the alternate basic regimens are shown here.  Didanosine (ddI) can cause pancreatitis, lactic acidosis, neuropathy, diarrhea, abdominal pain, and nausea.  Side effects for stavudine (d4T) include peripheral neuropathy, pancreatitis, increased liver function tests, anemia, neutropenia, headache, diarrhea, nausea, insomnia, and 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

**Notes:**
Drug interactions, toxicities, and side effects for expanded regimens should also be considered.  All protease inhibitors inhibit metabolism of non-sedating antihistamines and other hepatically metabolized drugs.  They also increase diabetes-related problems.  Indinavir may cause nausea, abdominal pain, and nephrolithiasis. The occurrence of nephrolithiasis may be limited by drinking at least 1.5 liters of fluid per 24-hour period.  Nelfinavir may accelerate the clearance of certain drugs, including oral contraceptives, and may cause diarrhea, nausea, abdominal pain, weakness, and 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

**Notes:**
Side effects for efavirenz include rash and nervous system problems, such as dizziness and insomnia.  Abacavir may cause nausea, diarrhea, anorexia, abdominal pain, fatigue, headache, insomnia, and 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

**Notes:**
Nevirapine is generally not recommended for use as HIV postexposure prophylaxis because of concerns about toxicity. Fulminant liver failure (one requiring a liver transplant) and hypersensitivity reaction were reported in healthcare personnel taking nevirapine. Including these case reports, the FDA has received 22 reports of serious adverse events related to nevirapine taken for postexposure prophylaxis. These adverse events were hepatotoxicity, skin rash, and rhabdomyloysis.  

## 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

**Notes:**
Follow-up testing of the exposed person may be appropriate. If the source was HIV positive, HIV testing of the exposed person should be performed at 6 weeks, 3 months, and 6 months postexposure. EIA is the standard test, and direct virus assays such as p24 antigen and PCR for HIV RNA are not recommended. Extending the follow-up testing to 12 months postexposure is recommended for healthcare personnel who become infected with HCV following an exposure to a source who is co-infected with HIV and HCV because of possible delay in HIV seroconversion, but is 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

**Notes:**
Besides follow-up serologic testing, additional monitoring for PEP toxicity is needed if postexposure prophylaxis is taken. A complete blood count and renal and hepatic profiles should be done at baseline and 2 weeks after starting PEP.  Additional follow-up testing should be performed if the PEP regimen includes a protease inhibitor. For example, exposed persons on indinavir should be monitored for hypoglycemia, crystalluria, hematuria, hemolytic anemia, and hepatitis.  The regimen should be discontinued or modified if toxicity is noted.  Expert consultation is encouraged if postexposure prophylaxis toxicity develops.

## 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*

**Notes:**
Postexposure counseling is recommended for the HIV-exposed person.  Information about the side effects of the postexposure prophylaxis drugs, and the signs and symptoms of acute HIV infection, such as fever, rash, and flu-like illness, should be provided.  In addition, the prevention of secondary transmission through sexual abstinence or use of condoms, and avoiding blood or tissue donation should be emphasized.  Finally, transmission of HIV and/or drugs through breast milk and postexposure prophylaxis drug risks should be discussed if the exposed person is breastfeeding. No work restriction is 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

**Notes:**
In summary, the updated recommendations for occupational HIV exposure management provide guidance on the use of new antiretroviral drugs and new combinations of drugs, and provide stronger statements regarding the unnecessary use of postexposure prophylaxis. The use of rapid testing for source patients is encouraged, and the use of direct virus assays for follow-up of exposed personnel is discouraged. Finally, follow-up evaluation is encouraged 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

**Notes:**
Practice recommendations to assist healthcare facilities implement the PHS guidelines for managing occupational exposures to bloodborne pathogens are summarized here.  They include the establishment of a bloodborne pathogen management policy, implementation of such policies (including training, hepatitis B vaccination, exposure reporting, and access to postexposure prophylaxis), establishment of laboratory capacity for bloodborne virus testing and the selection and use of appropriate postexposure prophylaxis 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)

**Notes:**
In addition, healthcare facilities should provide counseling for exposed personnel, monitor for adverse effects of postexposure prophylaxis and seroconversion, and monitor the exposure management programs, including elements such as the time between exposure and evaluation, testing of source persons, and completion of follow-up by exposed personnel.

## 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

**Notes:**
In conclusion, occupational exposure management is complex. Prevention is best, through hepatitis B immunization and avoiding occupational blood exposures. Additionally, the Division of Healthcare Quality Promotion (DHQP) invites all healthcare personnel and healthcare facilities to join in the challenge of eliminating needlestick injuries.

## Sources of Additional Information

- Division of Healthcare Quality Promotion
-    Phone: 800-893-0485
- 	Homepage:  http://www.cdc.gov/ncidod/hip/
- Hepatitis Hotline
- 	Phone: 888-443-7232
- 	Homepage: http://www.cdc.gov/hepatitis
- Needlestick!
- 	Homepage:http://www.needlestick.mednet.ucla.edu

**Notes:**
Additional information about the management of occupational exposures to bloodborne pathogens may be obtained at the websites listed here and/or by telephoning the Division of Healthcare Quality Promotion and the Division of Viral Hepatitis, both at CDC.  In addition, the Needlestick website, sponsored in part by CDC, is an interactive site to assist in the management and documentation of occupational exposures. 

## 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 website
- 	http://www.osha-slc.gov/SLTC/bloodbornepathogens/index.html

**Notes:**
Additional sources of information also include the National Institute for Occupational Safety and Health’s bloodborne pathogens website and the Occupational Safety and Health Administration’s bloodborne pathogens website.

## 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*

**Notes:**
Finally, a joint program of  the University of California at San Francisco, the Health Resources and Services Administration, and CDC is a national clinicians’ postexposure prophylaxis hotline called PEPline.  PEPline provides free consultation to clinicians treating occupational exposures to bloodborne pathogens. Its services are available 24 hours a day, 7 days a week.

## PREVENTION  IS PRIMARY!

*Protect patients...protect healthcare personnel...*
*promote quality healthcare!*

**Notes:**
Prevention is Primary.