Risks and recommendations for HIV occupational exposures.

The Public Health Service recently updated its recommendations for chemoprophylaxis after exposure to HIV. These recommendations correlate the use of antiretroviral agents with the risk of infection, which is determined by evaluating the exposure and the potential for transmission from the source patient.

Information on the treatment for patients infected with HIV has changed rapidly over the past several years, and recommendations for the prevention of HIV transmission after occupational exposures are no exception. In May 1998, updated recommendations on the prevention of occupational transmission of HIV were published as a result of new information, Food and Drag Administration approval of new antiretroviral agents, and a meeting of experts convened by the Centers for Disease Control and Prevention. Presented here are the Public Health Service recommendations for the use of these antiretroviral agents for postexposure prophylaxis (PEP). The Public Health Service recommendations for PEP are intended to provide guidance to physicians. They can be modified by local experts on a case-by-case basis. When possible, expert consultation is recommended.

Epidemiology of occupational exposures

Transmission of bloodborne pathogens is an occupational hazard for healthcare workers. Nationally, as of June 30, 1997, 52 healthcare workers became infected with HIV as a result of an occupational exposure. Twenty-four of these workers developed AIDS. The 52 healthcare workers include 21 nurses, 19 laboratory technicians, 6 physicians, 2 surgical technicians, 1 dialysis technician, 1 housekeeper/maintenance worker, 1 health aide/attendant, and 1 respiratory therapist[2] (see also "Needlesticks: Who pays the price when costs are cut on safety?" MLO, July 1998, p. 30).

The most common route of exposure for occupational HIV transmission is percutaneous (needlestick or other penetrating sharps-related event). Forty-five of the seroconversions occurred as a result of a percutaneous exposure, five occurred through a mucocutaneous exposure (mucous membrane and/or skin exposure), one occurred through a combined percutaneous and mucocutaneous exposure, and one route of exposure was unknown. Forty-six employees were exposed to HIV-infected blood, three were exposed to concentrated virus in the laboratory, one was exposed to visibly bloody body fluid, and one was exposed to an unspecified fluid. The objects involved in the percutaneous exposures include a hollow-bore needle (41), a broken glass vial (2), a scalpel (1), and an unknown sharp object.[2]

Workplace safety: How to protect yourself

Workplace safety includes the incorporation of infection control precautions, also known as standard precautions, into daily practice to prevent exposure to blood. These precautions include the appropriate use of personal protective equipment (e.g., gloves, eye protection, gowns) when contact with blood and other body fluids is anticipated. Needlestick and other sharps injuries may be prevented by changes in technique that eliminate the need for needles/sharps and/or by the use of safer devices. Needles should not be bent, recapped, or broken. Needles/sharps should be placed in a puncture resistant container to minimize the risk of exposure.[3,4]

The Occupational Safety and Health Administration requires that primary methods to decrease occupational risk include engineering controls.[5] A six-hospital study conducted by the CDC indicated that safety devices for phlebotomy, such as vacuum-tube blood collection devices and winged steel needles, significantly reduced the risk of percutaneous injury.[6]

New technology to obtain specimens for HIV testing may also decrease the risk of occupational exposure. An oral test kit received FDA approval in 1996 and a urine test was approved in 1998 (see News Worthy, MLO, August 1998, p. 10). These tests obviate the need to draw blood to test for HIV. Because no phlebotomy is required, and the patient can obtain the specimen, the risk of occupational exposure during specimen collection is less than with obtaining the classic blood specimen.[7]

What is an occupational exposure?

An occupational exposure is defined as skin, eye, mucous membrane, or parenteral contact with blood or other potentially infectious material. Parenteral contact includes piercing mucous membranes or the skin barrier through such events as a needlestick, human bite, cut, or abrasion. Blood is defined as human blood, human blood components, and products made from human blood. The other potentially infectious materials include the following human body fluids: semen, vaginal secretions, amniotic fluid, cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, saliva in dental procedures, any body fluid that is visibly contaminated with blood, and all body fluids in situations where it is difficult or impossible to differentiate between body fluids. Any unfixed tissue or organ (other than intact skin) from a human (living or dead); HIV-containing cell or tissue cultures, organ cultures, and culture medium or other solutions; and blood, organs, or other tissues from experimental animals with HIV-infection are also included in the category of other potentially infectious material.[5]

What is the risk of occupational exposures?

The CDC has been tracking occupational exposure to HIV. The average risk of HIV infection from all types of percutaneous exposures to HIV-infected blood is 0.3%.[8] The CDC conducted a case-control study to determine the risk of HIV infection from different types of percutaneous exposures. This case-control study showed that the risk of HIV infection exceeded 0.3% for exposures that involved one of the following: (1) a deep injury to the healthcare worker, (2) visible blood on the device that caused the injury, (3) if the device had been placed in the source patient's vascular system (e.g., a needle used for phlebotomy), or (4) if the source patient died as a result of AIDS within 60 days after exposure.(9)

The increased risk associated with these scenarios may be related to exposure to larger volumes of blood or to blood containing a higher titer of the HIV virus. However, the utility of viral load measurements from the source patient to estimate the risk of transmission based on the vital titer is unknown. Plasma vital load reflects only the level of cell-free virus in the blood. It does not reflect the level of cell-associated virus in the blood or the amount of virus present in compartments, such as lymphatic tissue. HIV transmission from persons with a viral load below detectable limits has been reported in the seroconversion of one healthcare worker and in instances of mother-to-infant transmission.[1,10,11]

The average risk of HIV infection after a mucous membrane or skin exposure is less than the risk associated with a percutaneous exposure. The average risk of HIV infection after a mucous membrane exposure is 0.1%. The average risk of HIV infection after a skin exposure is less than 0.1%. The risk for skin exposure may be increased if skin contact is prolonged, contact involves an extensive area of the skin, the integrity of the skin is not intact, and/or if the exposure involves a higher titer of HIV.[1]

Follow-up for occupational exposures

Employers need to provide healthcare workers with a system for prompt evaluation, counseling, and follow-up after an occupational exposure that may place the employee at risk for HIV infection. First aid should be administered immediately after an exposure. Puncture wounds and other cut injuries should be washed with soap and water. Exposure to oral and nasal mucosa should be decontaminated by flushing with water. Eyes should be irrigated with clean water and saline or sterile irrigants designed for flushing eyes. The exposure should be reported to the person or department (e.g., employee health, infection control) responsible for managing exposures.

Workers with occupational exposures to HIV should receive follow-up counseling and medical evaluation. HIV antibody tests should be performed at baseline and periodically for at least 6 months after exposure (e.g., 6 weeks, 12 weeks, and 6 months). The employee should be counseled on precautions to prevent secondary transmission of HIV.[12]

In some instances, appropriate postexposure management also includes the use of antiretroviral agents for PEP. If PEP is used, drug toxicity monitoring should be included in the medical management and follow-up of the employee. Although it is the employer's responsibility to offer PEP when it is appropriate, the employee can refuse it.

Postexposure prophylaxis: Does it work?

A multi-national study found that PEP with zidovudine (AZT, ZDV) may reduce the risk of HIV infection. The use of zidovudine PEP was shown to decrease the risk of HIV infection after a percutaneous exposure by 81%.[13] However, as with chemoprophylaxis measures for other infectious diseases, failures have occurred with zidovudine PEP.[5] The reason(s) zidovudine PEP failed to prevent HIV infection in at least 14 cases is not known; however, in one case, the virus was noted to be partially resistant to zidovudine.

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Recommendations for PEP have changed with the development and FDA approval of new antiretroviral agents, but other aspects of postexposure management (e.g., reporting exposures, counseling, and testing of both the exposed healthcare worker and source patient) have not changed.[9]

When should PEP start?

When PEP is indicated, it should be initiated promptly, preferably within 1-2 hours after the exposure. There are several reasons why PEP may not be started immediately, such as when an employee refuses the therapy. The interval after which PEP is not effective is unknown, however. Initiating PEP after a longer interval (e.g., 1-2 weeks) may be considered for exposures that represent an increased risk of transmission. Even if infection is not prevented, early treatment of HIV infection may be beneficial.[1]

The optimal duration of PEP is uncertain. The Public Health Services recommend 4 weeks of PEP because 4 weeks of zidovudine appeared protective in certain studies.[1,8]

The recommendations

Although these recommendations represent the most recent Public Health Service recommendations for PEP, they are always subject to change, PEP is not recommended for all types of occupational exposure to HIV because most occupational exposures do not result in HIV transmission. For many types of exposure, the risk of serious side effects may exceed the risk of HIV infection. Exposures with a lower risk of infection may not warrant the potential side effects of these agents. When discussing the use of PEP, the employee should be informed that: (1) knowledge about the efficacy and toxicity of PEP is limited; (2) for agents other than zidovudine, data are limited regarding toxicity in persons who are not HIV infected or who are pregnant; and (3) the employee can decline PEP.[1]

The risk from exposure. The first factor to consider is the exposure itself. Step 1 in the Figure shows how to determine the exposure code and its role in determining the PEP recommendations. Situations that pose a risk for bloodborne transmission and require further evaluation are:

1. Exposures to blood, fluid containing visible blood, or other potentially infectious fluid or tissue through a percutaneous injury or through contact with a mucous membrane.

2. Any direct contact (i.e., personal protective equipment either was not used or was ineffective in protecting skin or mucous membranes) with concentrated HIV in a research laboratory or production facility is considered an exposure that requires clinical evaluation to assess the need for PEP.[1]

3. For skin exposures, follow-up is indicated if it involves direct contact with a body fluid listed previously and if there is evidence of compromised skin integrity (e.g., dermatitis, abrasion, or open wound). However, if contact is prolonged or involves a large area of intact skin, postexposure follow-up may be considered on a case-by-case basis or when it is requested by the healthcare worker.[1]

4. For human bites, the clinical evaluation must consider possible exposure of both the bite recipient and the person who inflicted the bite. HIV transmission has rarely been reported by this route. If a bite results in blood exposure to either person involved, postexposure follow-up, including consideration of PEP, should be provided.[1]

Risk from the source patient. The second component in assessing the risk of transmission is to evaluate the source of the occupational exposure. Step 2 in the Figure shows how the information on the source patient is used to help determine the PEP recommendation. The source person should be evaluated for risk of HIV infection. This can be done through information available on the medical record at the time of the exposure (e.g., laboratory test results, admitting diagnosis, or medical history). Certain pieces of information from the source person may suggest or rule out possible HIV infection, such as prior HIV test results, results of past immunologic testing (e.g., CD4+ T-cell count), clinical symptoms (e.g., acute syndrome suggestive of HIV infection or undiagnosed immunodeficiency disease), and a history of possible HIV exposure (e.g., injection drug use, sexual contact with a known HIV-positive partner, unprotected sexual contact with multiple partners, or receipt of blood products prior to 1985).[1]

If the source is known to be infected with HIV, available information about the source's stage of infection (including asymptomatic or AIDS, CD4+ T-cell count, and viral load test results) as well as current and previous antiretroviral therapy should be considered when selecting PEP regimen. However, when PEP is indicated [ILLUSTRATION OMITTED], it should not be delayed while this information on infection status is being gathered. if necessary, changes in the PEP regimen can be made after it has been started.[1]

If the HIV status of the source person is unknown, the source person should be informed of the incident. If consent is obtained, testing should be done with appropriate pre- and post-test counseling. Confidentiality regarding the HIV status of the source person should be maintained at all times.[1]

If the source agrees to HIV testing, the testing should be done as soon as possible. Physicians and infection control practitioners may request information from the laboratory regarding the most appropriate FDA-approved HIV antibody test to expedite these results. An FDA-approved rapid HIV antibody test should be considered for use in these situations, especially if enzyme immunoassay testing cannot be completed within 24-48 hours.[1]

If the source is HIV-seronegative and has no clinical evidence of AIDS or symptoms of HIV infection, no further testing of the source is indicated. It is unclear whether follow-up testing of a source who engaged in a high-risk behavior within the last 3 to 6 months is useful in the postexposure management of healthcare workers. Healthcare workers who become infected generally seroconvert before repeat testing of the source would normally be performed.[1]

If the exposure source is unknown, information about where and under what circumstances the exposure occurred should be assessed epidemiologically for the risk of transmission. Certain situations may suggest an increased or decreased risk of transmission. The prevalence of HIV in the population group (e.g., institution or community) is important. For example, an exposure that occurs in a geographic area where injection drug use is common or on an AIDS unit in a healthcare facility would be considered to have an epidemiologically increased risk for transmission than in a nursing home for the elderly where no known HIV-infected residents are present. Decisions regarding appropriate management should be individualized based on the risk assessment.[1]

HIV testing of needles or other instruments associated with an exposure, regardless of whether the source is known, is not recommended. The reliability and interpretation of findings in such circumstances are unknown.[1]

Medications used for PEP

After an occupational exposure, PEP should be recommended based on the risk presented by the exposure and information about the source. Most HIV exposures will warrant only a basic two-drug regimen, using two nucleoside reverse transcriptase inhibitors, usually zidovudine and lamivudine (3TC). The addition of a third drug as part of an expanded regimen, usually a protease inhibitor such as indinavir (IDV) or nelfinavir (NEL), should be considered for exposures that pose an increased risk of transmission or where resistance to other drugs used for PEP is known or suspected. Whenever possible, the regimens should be implemented in consultation with experts in antiretroviral therapy and HIV transmission. The Table describes the basic and expanded regimens.[1]

Zidovudine should be considered for all PEP regimens because it is the only agent for which data support the efficacy of PEP in a clinical setting. Lamivudine should usually be added to a regimen that includes zidovudine because it increases antiretroviral activity and activity against many zidovudine-resistant strains. A protease inhibitor should be added to the treatment regimen for exposures with a high risk of transmission. However, individual clinicians may prefer other combinations of drugs based on local knowledge and experience in treating HIV disease.[1]

Currently, the FDA has approved zidovudine, lamivudine, indinavir, and nelfinavir for the treatment of HIV infection, but not for PEP. However, physicians may prescribe any FDA-approved medication when, in their professional judgment, use of the medication is clinically indicated.

Monitoring and side effects

If PEP is used, drug toxicity monitoring needs to be performed. This should include a complete blood count and renal and hepatic chemical function tests at baseline and 2 weeks after starting PEP. Monitoring for hyperglycemia should be included for PEP regimens that include a protease inhibitor. If indinavir is included, monitoring for crystalluria, hematuria, hemolytic anemia, and hepatitis should also be performed. If subjective or objective toxicity is noted, dose reduction or drug substitution should be considered with expert consultation. Further diagnostic studies may be indicated. Healthcare workers who become infected with HIV should be counseled on and receive the appropriate medical care.

Side effects may make it difficult to remain on PEP. Preliminary information from healthcare workers taking zidovudine and lamivudine for PEP, with or without a protease inhibitor, suggests that 50-90% report subjective side effects. These side effects caused 24-36% of healthcare workers to stop PEP. Common symptoms associated with these medications are headache, malaise, fatigue, or insomnia. However, more serious side effects including kidney stones, hepatitis, and pancytopenia have been reported with combination PEP. In general, the frequency of these side effects has not been greater when these agents have been used in combination. The symptoms can frequently be managed without changing the regimen by prescribing antimotility, anti-emetic, or other medications that target specific symptoms. In other situations, modifying the dose interval (i.e., taking a lower dose more frequently during the day, as recommended by the manufacturer), may make it easier for people to stay on PEP.

All of the FDA-approved protease inhibitors have potentially serious drug interactions. Therefore, it is extremely important for healthcare workers to let their physicians know about all medications before a protease inhibitor is prescribed.

Voluntary registry for PEP

Currently, only limited data are available on the side effects and toxicity of antiretroviral agents in people who are not HIV-infected. To learn more about the safety and outcomes associated with PEP, healthcare providers are encouraged to enroll all workers who receive PEP in a voluntary, anonymous registry. The registry is a collaborative effort among the CDC, Glaxo Wellcome Inc., and Merck and Co., Inc. The specific information requested in the registry includes the exposure, the antiretroviral agents being taken, abnormal laboratory findings, and physical symptoms associated with using these antiretroviral agents. Healthcare workers and providers can learn more about the registry by calling 1-888-PEP4HIV (1888-737-4448).[9]

Additional information on healthcare worker occupational exposure

Information on HIV PEP is available from multiple sources. These include[9]:

1. The CDC's Web site at http://www.cdc.gov

2. The CDC's fax information service at 40+332-4565

3. The National AIDS Clearinghouse at 1-800-458-5231

4. The HIV/AIDS Treatment Information Service at 1-800-448-0440.

Clinicians can seek consultation on HIV PEP from the National Clinicians Postexposure Hotline at 1-888-448-4911.[1]

RELATED ARTICLE: Closing the transfusion loop: The Immucor I-TRAC System

INTRODUCTION/BACKGROUND

Over the last several years, numerous efforts have been directed at decreasing the risk of transmission of viruses through transfusion. The blood supply is safer due to the efforts of many scientists and policies to screen or reject high risk donors. ABO-related transfusion fatalities due to misidentification of patient crossmatch specimens or recipients has remained virtually constant over the last several decades. The reason for this is that the system for collecting a sample of blood, crossmatching RBC components, and delivering and administering the blood which incorporates checks and safeguards is dependent on human performance. The omission of one or more key safety steps can allow misidentification, and thus a transfusion accident to occur. Immucor, Inc., partnered with Healthcare-ID, has developed a solution that relies on electronic verification of the patient at the bedside before specimen collection or administration of blood or blood components rather than on human nature.

IMMUCOR SOLUTION:

The Immucor I-TRAC system:

* Manages from specimen collection through automated patient testing to administration of blood and blood components.

* Uniquely identifies each patient by using a bar coded patient name and medical record patient identification number.

* Uses hand-held portable terminals and portable printers to label specimens at the bedside and to electronically compare the patient wristband and the bar coded compatibility label on the unit of blood and/or component selected for the patient.

* Electronically allows for samples to be tested for group and screen using Immucor automation that has the ability to electronically download results to the laboratory information system.

* Electronically confirms that the unit number assigned by the donor center matches the unit number on the bar coded compatibility label.

* Performs electronic checks at the site of each transfusion and "flags" the transfusionists with the occurrence of mismatched information.

* Captures information on the transfusion episode and prints it at the patient bedside or allows for electronic transfer to the blood bank

* Provides a system for monitoring the entire process.

PROCESS

Sample Management and Testing

Step A. Portable data terminal (PDT) scans patient's wristband at the bedside. Specimen labels are printed or verified for patient sample and requisition at the bedside using a portable printer.

Step B. Immucor automated system (ABS2000) performs ABO/Rh and antibody screen on patient sample and electronically transfers results to Laboratory Information System.

Step C. Blood is selected for patient by technologist. Crossmatch is performed electronically, serologically, or on the Immucor ABS2000.

Step D. A bar coded compatibility label is produced using the Immucor bar code print program or LIS and attached to the blood or blood component.

Step E. Blood or blood component is issued from the blood bank to the patient.

Administration of Blood and Blood Components

Step I. Portable data terminal (PDT) scans the patient's wristband and the bar coded compatibility label at the bedside. Verification is made of the following:

* Patient's identification (wristband) and bar coded compatibility label (patient ID number).

* Patient's identification (wristband) and bar coded compatibility label (patient name).

* Blood or blood component identification (unit ID number) and bar coded compatibility label (unit ID number).

Step II. PDT records start and completion date/time of transfusion and evidence of transfusion reaction.

Step III. Transfusion event details are documented on a report and printed at the bedside using the portable printer. Details can be transmitted to the blood bank.

(Note: I-TRAC Plus captures vital signs.)

CONCLUSION

* The I-TRAC system is the first integrated system that verifies and tracks from specimen collection through testing (via blood bank automation) and administration of blood and blood components to "dose the transfusion loop."

* Use of the I-TRAC system will improve safety of transfusion and should reduce avoidable ABO fatal transfusion fatalities due to misidentification of the sample, the unit, or the recipient.

References

1. Centers for Disease Control and Prevention. Public Health Service guidelines for the management of healthcare worker exposures to HIV and recommendations for postexposure prophylaxis. MMWR. 1998; 47(RR-7):1-33.

2. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report. 1997;7(9): 15.

3. Hospital Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. Guideline for isolation precautions in hospitals, Part II. Recommendations for isolation precautions in hospitals. Am J Infect Control. 1996;24: 32-45.

4. Garner JS. Guideline for isolation precautions in hospitals. Infect Control Hosp Epidemiol. 1996;17:53-80.

5. Occupational Safety and Health Administration. Occupational exposure to bloodborne pathogens: Final rule. Federal Register 1991 ;56:64004-64182.

6. Centers for Disease Control and Prevention. Evaluation of safety devices for preventing percutaneous injuries among healthcare workers during phlebotomy procedures: Minneapolis-St. Paul, New York City, and San Francisco, 1993-1995. MMWR. 1997;46:21-25.

7. Gallo D, George JR, Fitchen JH, Goldstein AS, Hindahl MS. Evaluation of a system using oral mucosal transudate for HIV-1 antibody screening and confirmatory testing. JAMA. 1997;277:254-258.

8. Tokars JI, Marcus R, Culver DH, et al. Surveillance of HIV infection and zidovudine use among healthcare workers after occupational exposure to HIV infected blood. Ann Intern Med. 1993;118:913-919.

9. Centers for Disease Control and Prevention. Case-control study of HIV seroconversion in healthcare workers after percutaneous exposure to HIV-infected blood: France, United Kingdom, and United States, January 1988-August 1994. MMWR. 1995; 44:929-933.

10. Sperling RS, Shapiro DE, Coombs RW, et al. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. N Engl J Med. 1996;335: 1621-1629.

11. Ippolito G, Puro V, De Carli G, The Italian Study Group on Occupational Risk of HIV Infection. The risk of occupational human immunodeficiency virus infection in healthcare workers. Arch Intern Med. 1993; 153:1451-1458.

12. Centers for Disease Control and Prevention. Public Health Service statement on management of occupational exposure to human immunodeficiency virus, including considerations regarding zidovudine post exposure use. MMWR. 1990;39(RR-1): 1-14.

13. Cardo DM, Culver DH, Cieselski CA, et al. A case-control study of HIV seroconversion in healthcare workers after percutaneous exposure. N Engl J Med. 1997; 337:1485-1490.

Sindy Paul is medical director, Samuel Costa is program manager HIV/AIDS surveillance, and Leah Ziskin is deputy commissioner. All authors are employed at the New Jersey Department of Health and Senior Services, Division of AIDS Prevention and Control, Trenton, NJ.