[Table of Contents]

Volume: 23S2 • March 1997

AN INTEGRATED PROTOCOL TO MANAGE HEALTH CARE WORKERS EXPOSED TO BLOODBORNE PATHOGENS

Appendix

Post-Exposure Chemoprophylaxis Guidelines for Occupational Exposure to HIV

Background

Until recently, the information available on the post-exposure use of chemoprophylactic agents such as zidovudine (ZDV) has not been sufficient to either recommend or discourage their use as part of the exposure protocol in Canada ⁽⁸⁾ or the United States ⁽¹⁶⁾. The decision to use ZDV has been left to the discretion of the patient and the treating physician, taking into consideration the details of the exposure, side effects, and uncertain efficacy of ZDV. A number of centres with extensive experience in the area of occupational exposure, for example the San Francisco General Hospital, have encouraged the use of ZDV for massive exposures and definite parenteral exposures, and also for probable parenteral exposures especially if the source patient has AIDS ^(17,18).

A recent case-control study identified three categories of factors associated with seroconversion among occupational exposures to HIV: a group of variables related to volume of blood injected (deep injury, procedure involving a needle placed directly into source patient's vein or artery, and visible contamination of sharp with patient's blood); terminal HIV illness in source patient; and non-use of ZDV post-exposure prophylaxis ⁽¹⁹⁾. This study illustrates the importance of the specific circumstances of the exposure in determining the risk of transmission and supports the efficacy of ZDV for post-exposure prophylaxis. Although transmission has been known to occur despite ZDV post-exposure prophylaxis (PEP) ⁽²⁰⁾, the case-control study suggests that ZDV PEP reduces the risk of HIV seroconversion, following percutaneous exposure, by about 80%. ZDV has also been shown to reduce the rate of transmission from mother to infant by 67% when given to HIV-infected pregnant women and their infants ⁽²¹⁾ , although it is not clear how much of this effect is due to a direct PEP-like effect on the infant. Some animal studies also show that PEP with ZDV or other nucleosides can prevent retroviral infection ^(22,23).

There are no data on the effectiveness or side effects of other anti-retroviral agents or combined therapy for PEP. However, it is tempting to make an analogy with the treatment of HIV-infected patients where data show that combination therapies are more effective than ZDV alone in reducing viral load ^(24,25). Combination therapy could also be useful in situations where drug resistance is present. The use of combination therapy for PEP therefore has some biologic plausibility. However, it is not known if the side-effects of these drugs seen in HIV-infected patients will be the same in HIV-uninfected patients. The potential benefits and risks of PEP must be carefully considered. The appeal of implementing post-exposure treatment immediately, i.e. to err on the side of caution, must be tempered by the facts that the toxicities of these new drugs in the post-exposure setting are not yet well understood and that most exposures do not result in the transmission of HIV (average risk of infection after percutaneous exposure to HIV-infected blood is 0.3%) ⁽²⁰⁾.

The provisional recommendations noted below for PEP are fairly general and will need to be updated periodically as new data become available. Their general nature will allow needed flexibility in their implementation since regions of the country differ in the availability and use of the various antiretroviral agents. These guidelines should be implemented in consultation with local or regional experts in the care and treatment of HIV disease.

Provisional Recommendations for HIV Post-Exposure Chemoprophylaxis

The use of PEP for occupational exposure to HIV is either recommended, offered, or not offered depending on the circumstances of the exposure and the characteristics of the source.

PEP is recommended for the following exposures that carry an increased risk for transmission of HIV:

• percutaneous, mucous membrane, or non-intact skin (see Section 2.2) exposure to concentrated virus in a research laboratory or similar facility; or

• percutaneous exposures to potentially infectious blood or body fluids (see Section 2.1) which involve deep injury, injection of source patient's blood or body fluid, a needle placed directly in source patient's blood vessel, or source patient with high viral titre (as in acute retroviral illness or terminal HIV disease).

PEP is offered (not actively recommended) to the HCW, with appropriate counselling for situations that involve less risk of transmission of HIV, for the following categories of exposures to potentially infectious blood or body fluids (see Section 2.1):

• percutaneous exposures that do not involve deep injury, injection of source patient's blood or body fluid, a needle placed directly in source patient's blood vessel, or source patient with high viral titre as in acute retroviral or terminal illness. (An example would be a superficial injury from a solid suture needle used in a source patient with asymptomatic HIV infection.); or

• mucous membrane or non-intact skin exposures. (The larger the area of skin exposed and the longer the duration time of exposure, the more important it is to verify that all the relevant skin area is intact).

The optimal regimen for PEP is controversial and may vary with local circumstances and the changing availability and use of antiretroviral drugs. However, ZDV should be included in all PEP regimens because there are data to support its efficacy and its side effects are well known. The suggested ZDV regimen is 200 mg three times a day for 4 weeks. At least one other agent should be added to the PEP regimen to take advantage of the possibly greater antiretroviral activity of drug combinations and to address the possibility of a ZDV-resistant strain of HIV in the source patient.

The specific drug to be added to ZDV will depend on local availability and expert clinical advice. Possibilities include another nucleoside reverse transcriptase inhibitor, such as lamivudine (3TC) or zalcitibine (ddC); non-nucleoside reverse transcriptase inhibitors, such as nevirapine or delavirdine; or protease inhibitors, such as indinavir or saquinavir. For example, the United States Centers for Disease Control and Prevention (CDC) recommends lamivudine as the second drug to be added (150 mg two times a day for 4 weeks) due to the demonstrated effect of this combination on viral load and the relatively few side effects in HIV-infected patients ⁽²⁶⁾. The addition of a third drug may be considered for certain exposure situations, such as very high-risk exposure or cases where the patient has been on multiple, long-term therapy and multi-drug resistance is considered likely. For example, CDC recommends adding indinavir (800 mg three times a day for 4 weeks) as the third drug for percutaneous exposures that involve both a large volume of blood and a source patient with high HIV viral titre ⁽²⁶⁾. The International AIDS Society suggests the use of two drugs that have not been used in the source patient ⁽²⁵⁾.

It is recognized, however, that PEP guidelines cannot be rigid at this time of rapidly evolving information; flexibility must be maintained on a case-by-case basis, regionally, and over time. These guidelines for post-exposure prophylaxis for HIV will be modified and updated as new information becomes available. At present, combination therapy with at least two drugs is recommended for PEP, but local expert advice should be sought regarding the potential risks and benefit of a two-drug versus a three-drug regimen and the specific drug choices. Expert advice should also be sought regarding frequency of medical follow-up for cases using PEP to monitor for drug tolerances and toxicities.

It is recommended that each institution give consideration to establishing a specific regimen based on local drug availability and resistance patterns. Since maximum benefit is likely to be obtained when prophylaxis is started immediately, it is further recommended that institutions consider making standard prophylaxis kits readily available for use in occupational HIV exposures.

[Previous] [Table of Contents] [Next]