Prophylaxis After Occupational Exposure To
Human Immunodeficiency Virus (HIV)

Alexander G. Vandevelde, M.D.
Alexander Vandevelde, M.D. is Associate Professor of Medicine and Chief of the
Travel Medicine Section of the University of Florida Health Science Center / Jacksonville.
He is also Director of Infection Control for University Medical Center.

Without doubt, the shamen and healers of bygone eras must have known that during their ceremonies to restore health, they would run the risk of contracting some of the diseases of primitive man. The grotesque hoods with beak-like appendages that physicians wore in the Middle Ages during the plague epidemics were a vain attempt to avoid breathing the "ethereal vapors" that were supposed to emanate from the victims' body and transmit the disease. Our understanding of the chain of transmission of communicable diseases has grown to a point that we are able to protect the healthcare worker (HCW) under most circumstances. But, accidents happen!

Among the bloodborne pathogens that pose a risk to HCWs, the danger of contracting HIV is much lower than that of the hepatotropic viruses (less than 0.5% following a needlestick, less than 0.1% after mucosal exposure for HIV vs. approximately a 20% risk of hepatitis B following parenteral exposure).¹ Nevertheless, we are all extremely concerned about acquiring HIV. Occupational transmission has been reported after exposure to HIV-infected blood, not only through percutaneous inoculation, but also through contact of blood with mucous membranes and nonintact skin.²

Prevention

Preventing exposure of any type is an important element of workplace safety. Precautions formulated by the Occupational Safety and Health Administration (OSHA) for bloodborne pathogens are mandated, especially universal/standard precautions, gloving, safe handling of needles and the use of needleless infusion systems. (See Hospital Employee Health, May 1999, pp. 51-3.)

Postexposure Prophylaxis (PEP)

During the past decade, evidence has emerged that supports the notion that antiretroviral drugs are 80% effective in preventing HIV infection after occupational exposure to the virus.³ However, absolute proof does not exist yet.

In the sequence of events after an HIV exposure the dendritic/Langerhans macrophages play a pivotal role.⁴ These dendritic macrophages, located below the skin or mucosal surfaces, rapidly pick up the deposited HIV. Then, these cells very efficiently hand over the virus to susceptible T-lymphocytes (CD₄ cells).

Certain antiretrovirals, particularly zidovudine, not only inhibit HIV replication, but also block the handing-over of HIV from the dendritic cells to the susceptible T-lymphocytes. Subsequently, these virus-laden dendritic macrophages are eradicated by the host's cell-mediated immunity (CMI). The elimination processes are apoptosis and cytolysis induced by antiviral cytotoxic T-lymphocytes which belong to the CD₈ family of cells.⁵

There is no doubt that CMI plays an important role in the defense against HIV. In retroviral studies with mice, zidovudine (ZDV) works well only when CMI is intact. Exposed, but uninfected healthcare workers have interleukin-2-producing lymphocytes when exposed to HIV antigens. They also possess cytotoxic T-lymhocytes that respond with the production of cytolytic compounds when brought in contact with HIV envelope peptides.

Animal studies have taught us that chemoprophylactic therapy is efficacious in preventing retroviral infections under certain circumstances: 1) in small inoculum sizes; 2) in animals that possess a normal cell-mediated immunity; 3) when given relatively soon after the inoculation (<24 hours); and 4) when the duration of therapy is long enough (4 weeks).⁴

For ethical reasons, human studies to directly answer the question if PEP is efficient will never be done in a prospective, double-blinded and placebo-controlled protocol. However, the results of certain completed studies can be found relevant and extrapolated to the situation of the exposed HCW. Vertical transmission of HIV infection from mother to her newborn child has been greatly reduced by giving ZDV before birth and during labor, and also to the neonate for 6 weeks after birth. The ZDV given to the newborn is like treating an incubating infection by preemptive therapy.

One important retrospective study retraced the circumstances of how 33 HCWs contracted HIV infection on the job.^3,6 These were workers matched with 665 control HCWs who were also exposed to HIV, but were uninfected. Five factors were found to be associated with increased risk: 1) a deep injury; 2) visible blood of the source patient on the device; 3) a device that has been placed in the source patient's artery or vein, especially a hollow-bore needle; 4) terminal illness of the source-patient; and 5) lack of postexposure prophylaxis. From a practical point of view, a combination of 2 or more of these risk factors should be considered as a high-risk exposure. The authors felt that the administration of ZDV was associated with an 80% reduction of the risk for occupational HIV infection.

Definition Of A Dangerous Exposure

Since there is great emotional impact among HCWs after any type of exposure to HIV-tainted blood, one needs to define what is a high risk exposure (see previous paragraph). Any contact with HIV-infected blood or bloody body fluids is dangerous for transmission if it occurs by percutaneous inoculation, deposition of such blood upon a mucous membrane, or contact with skin surface made nonintact by abrasions, erosions or wounds. Short contacts involving blood, urine, feces, secretions or excretions with intact skin are not considered dangerous exposures.

The risk of each exposure varies. A hollow-bore needle is more dangerous than a solid suture needle. The greater the amount of inoculated blood, the greater the risk of HIV transmission. Blood of a source patient suffering from terminal AIDS with a high HIV viral load in plasma poses a greater risk than patients responding well to antiretroviral therapy and who are asymptomatic.

Management After Exposure

The first order of business after first aid¹ to the exposure site is duely reporting and documenting the incident with all the necessary information, including date and time, name of the source patient, the involved device, the exposure fluid with an estimate of the amount and the circumstances.

Second, the healthcare worker must be evaluated without delay, that is to say within 2 hours, by employee health clinic personnel or by stand-in designated persons during off-hours and in clinics without a structured employee health division. These services should be available for 24 hours per day and all personnel involved should be trained and be familiar with the established standard operating procedures. An initial evaluation should retrace the details of the exposure, as mentioned above, and a decision should be made if that particular exposure qualifies as a risky exposure.

Third, if the exposure carries a certain risk of HIV transmission, then antiretroviral therapy should be offered and highly recommended if the risk is high (Table 1). This postexposure prophylaxis (PEP) includes the nucleoside reverse transcriptase inhibitors zidovudine (ZDV) and lamivudine (3TC) as a basic regimen; if the regimen has to be expanded one should add a protease inhibitor (indinavir or nelfinavir). In our institution, we usually prescribe a three-drug regimen. These drugs should be taken for 4 weeks, and the HCW is counseled about the side-effects of the medications (Table 2). Follow-up visits are necessary to evaluate signs of drug toxicity. If other choices of antiretroviral agents are contemplated, ZDV should always be included in all regimens because it is the only agent with proven efficacy. Although the long-term side-effects of the antiretroviral drugs can be significant, such side-effects are usually not encountered when the drugs are only given for 4 weeks.⁶ Combination therapy has also been well tolerated to a point that most HCWs on PEP have been able to finish their 4-week course.

Table 1. Recommendations For Chemoprophylaxis After Occupational Exposure To HIV  (Adapted from Reference 7)

Type of Exposure

Source Material

Antiretroviral Prophylaxis¹

Antiviral Regimen²

Highest risk
Increased risk
Some risk

Fluid with visible blood, other potentially infectious fluid⁵, or tissue

Other non-infectious body fluid, e.g. urine

Recommended
Recommended
Offered

Offered

Not offered

ZDV + 3TC + a PI
ZDV + 3TC + a PI
ZDV + 3TC + a PI ⁴

ZDV + 3TC + a PI ⁴

^{-----------------------}

Fluid containing visible blood, other potentially infectious fluid⁵ or tissue

Other non-infectious body fluid, e.g. urine

Offered

Not offered

ZDV + 3TC

^{-----------------------}

Fluid containing visible blood, other potentially infectious fluid⁵ or tissue

Other non-infectious body fluid, e.g. urine

Offered

Not offered

ZDV + 3TC

^{--------------------------}

1. Explanation of terms: Recommended means that postexposure prophylaxis (PEP) should be recommended with counseling. Offered connotes that PEP should be offered with counseling. With not offered, PEP should not be offered because these are not occupational exposures to HIV.
2. Regimens: Zidovudine (ZDV) (300 mg bid); lamivudine (3TC) (150 mg bid) with or without a protease inhibitor (PI). Initially, the Center for Disease Control and Prevention (CDC) recommended indinavir (800 mg tid) and this recommendation still stands. However, the CDC now also recommends nelfinavir (750 mg tid) as an alternate PI. Other regimens can be used, but they should be reviewed on a case-by-case basis for HCWs who cannot tolerate the recommended regimens and when possible resistant HIV strains are involved. However, we do not know the impact of resistant strains.
3. Risk assessment: Highest risk for HIV transmission is seen in exposures involving both a large volume of blood and blood with a high HIV titer. The most common accident is a deep injury with a large-diameter hollow needle previously used in the source patient's vein or artery, especially when the penetration involves an injection of source patient's blood. Increased risk is encountered either with exposure to a large volume of blood (visible blood) or to blood with a high titer of HIV. There is some risk when the exposure involves a small volume of blood with a low HIV titer, e.g. a solid suture needle injury through a glove from a source patient with asymptomatic HIV infection.
4. Possible toxicity of additional drug may not be warranted.
5. Infectious fluids include semen, vaginal secretions, cerebrospinal, synovial, peritoneal, pericardial, and amniotic fluids. Breast milk, presumably also contaminated in patients with HIV, has not been involved with these types of accidents.
6. For skin, risk is increased for exposures involving a high titer of HIV, prolonged contact, an extensive area, or an area where skin integrity is visibly compromised. For skin exposures without increased risk, the risk for drug toxicity outweighs the benefit of PEP.

Table 2. First-Line Drugs For HIV Post-Exposure Prophylaxis (PEP) (Adapted from Reference 1)

Fourth, the HCW should be tested for HIV on the day of the accident and again at 6 weeks, 3 months and 6 months. Some experts even recommend a last test at 12 months, especially after an expanded drug regimen, which may delay the appearance of antibodies to HIV.

Fifth, if the positive status of the source-patient is known, one should find out the T-helper status (CD₄ count), the HIV viral load and the stage of the HIV disease, especially in cases of terminal AIDS. Viral resistance towards antiretrovirals should be evaluated by reviewing the source patient medical record. The knowledge of these data will make the risk assessment easier. If the HIV status is not known, yet the patient seems to be at high risk for having HIV infection, blood of the source patient should be tested

after the patient has been informed about an exposure accident. The rules of confidentiality of our state should be observed. The patient should receive pre-test HIV counseling, after which the great majority of patients will give testing permission. If the patient does not give testing consent, plasma or serum obtained for non-HIV-related blood work may be considereed for testing. While all this data gathering about the source person is going on, one should not delay the start of drug prophylaxis. If it seems to be a high-risk exposure, start an expanded regimen. If after a few days it becomes clear that the risk was overestimated, one can always withdraw the protease inhibitor.

Lastly, the HCW involved in an exposure accident should have easy access to employee health resources. Many questions, some related to anxiety, will come up and should be answered immediately. Counseling about prognosis and side-effects of drugs, and coaching is necessary. Couples should refrain from intercourse or use condoms up to six months after exposure. Pregnancy is not a contraindication for PEP, but the decision to accept PEP should remain in the hands of the exposed worker. The older and recommended drugs have not caused discernible teratogenic effects. Pregnant HCWs need to be informed that zidovudine is the only antiretroviral proven to be effective for the protection of the fetus. However, on theoretical grounds, transmission of HIV can be inhibited more by a combination of drugs (zidovudine with lamivudine). Coaching a pregnant woman is warranted since the side-effects of the drugs can aggravate the nausea associated with pregnancy.

Remaining Problems

There is an underreporting of occupational exposures to blood. Underreporting may lead to limitation in possible workers' compensation benefits, or to failure of administering PEP.

There is the question of resistance of HIV of the source patient to the antiretrovirals used in PEP. We know that the ZDV is still effective in preventing vertical transmission despite the facts that in many pregnant women the virus was
resistant to ZDV. After consultation and case review, an agent from a class of drugs which the source patient has not received may be considered. However, the recommended regimens that have proven effective should remain a standard of care in most cases.

Conclusion

An exposure to HIV by a HCW is a medical as well as a psychological emergency. Within a matter of 1 to 2 hours, the type of exposure should be determined and after counseling and if indicated, PEP should be started without delay. Certain data have to be gathered from the source patient. The HCW needs to be tested for HIV seroconversion up to 6 months, possibly 12 months after the accident. Counseling and follow-up care for health care workers exposed to HIV should be available.

References

1. CDC. Public Health Service guidelines for the management of health-care worker exposures to HIV and recommendations for postexposure prophylaxis. MMWR. 1998; 47(Nr. RR-7):1-33.
2. Ippolito G, Puro V, Heptonstall J, Jagger J, De Carl G, Petrosillo N. Occupational human immunodeficiency virus infection in health care workers: worldwide cases through September 1997. Clin Infect Dis. 1999; 28:365-83.
3. Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R et al, and the Centers for Disease Control and Prevention Needlestick Surveillance Group. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. N Engl J Med. 1997; 337:1485-90.
4. Henderson DK. Grand rounds at the Clinical Center of the National Institutes of Health: Postexposure chemoprophylaxis for occupational exposures to human immunodeficiency virus. JAMA. 1999; 281:931-6.
5. Yang OO. CD8 T cells in HIV infection: mechanism of immunity. Hospital Practice. 1998; Nov 15:105-27.
6. Henderson DK. Editorials. Postexposure treatment of HIV: taking some risks for safety's sake. N Engl J Med. 1997; 337:1542-3.
7. CDC. Update: Provisional Public Health Service recommendations for chemoprophylaxis after occupational exposure to HIV. MMWR. 1996; 45:468-72.
8. Vandevelde AG and Amin BS. When drugs don't mix in HIV-1-infected patients: clinical pharmacology and drug interactions of agents used to treat HIV-1 infection. Jacksonville Med. 1998; 49:360-4.

August, 1999/ Jacksonville Medicine

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