November 1996
Volume 60 |
Number 11
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| Occupational Exposure
to HIV: Chemoprophylaxis Reconsidered |
Samuel C. Hughes, M.D., Chair
Task Force on Infection Control
Committee on Occupational Health of Operating Room Personnel
Human immunodeficiency virus (HIV) was unknown and unnamed in
1981, when the report appeared of four cases of Pneumocystis
carinii in homosexual men.[1] By the
end of 1995, however, 74,180 cases of acquired immunodeficiency
syndrome (AIDS) were reported for that year alone in the United
States, with women representing approximately 19 percent of the
total.[2] From 1981 through 1995, there have
been 513,486 cases of AIDS reported to the Centers for Disease
Control and Prevention (CDC) and 315,928 deaths through December
1995.
Unfortunately, AIDS is here to stay and is arguably the most
serious occupational risk faced by anesthesiologists, even though
the actual incidence of work-related infection is extremely low.
Through the end of 1995, there were 49 documented occupational
transmissions (six physicians) and 102 possible occupational transmissions
(10 physicians) of HIV, according to the CDC. These figures represent
all health care workers (HCWs) and the total cases since the epidemic
began. However, preventing occupationally acquired HIV remains
vital. Given the large number of HIV-infected patients nationwide
estimated to be as high as 1.5 million, it is difficult to imagine
a practice in which occupational exposure does not exist to some
extent.
Recent data concerning the risk of occupationally acquired HIV
infection and recommendations from the Public Health Service for
the potential of chemoprophylaxis have significant implications
for anesthesiologists and other HCWs.[3]
The Task Force on Infection Control of the ASA Committee on Occupational
Health of Operating Room Personnel felt that an early notice of
these events would be beneficial to anesthesiologists. The revised
recommendations suggest the use of multidrug (two to three drugs)
antiretroviral prophylaxis after occupational exposure in certain
circumstances.[4]
Background
Preventing blood exposure is the primary means of reducing the
risk for occupationally acquired HIV infection. Blood exposure
by the anesthesiologist can and should be minimal if standard
preventative techniques are used. These techniques are outlined
and discussed in ASA's "Recommendations for Infection Control
for the Practice of Anesthesiology." However, exposure to
blood can and does occur. The potential of chemoprophylaxis to
prevent HIV infection after accidental occupational exposure has
been controversial, but new information suggests that zidovudine
(ZDV), formerly known as AZT, postexposure prophylaxis (PEP) may
reduce the risk of HIV infection.
Data collected from multiple centers demonstrated that ZDV PEP
was associated with a decrease of nearly 80 percent in the risk
for HIV seroconversion after percutaneous exposure to HIV-infected
blood.[3] This concept is also supported
by the effective use of ZDV prophylaxis in the parturient to reduce
newborn HIV infection. A 67-percent reduction in perinatal HIV
transmission was observed. These results have prompted the Public
Health Service interagency group comprised of representatives
from the CDC, the Food and Drug Administration (FDA), the Health
Resources and Service Administration and the National Institutes
of Health (NIH) to update its recommendations on the management
of occupational exposure to HIV and PEP.
How Did the Changes Come About?
The results of the case control study suggested that "the
risk for HIV infection among HCWs who used ZDV (as prophylaxis
after occupational HIV exposure) was reduced by approximately
79 percent."[3] While the study is not
without flaws, it also better established risk factors for HIV
infection. The risk was increased if the exposure was characterized
by:
- a deep injury to an HCW;
- visible blood on the device causing injury;
- a device previously placed in the source patient's vein or
artery (e.g., a catheter stylet needle); or
- a source patient presumed to have a high HIV titer (as in
late stages of the disease).
The risk of an HIV infection after mucous membrane or skin exposure
to HIV-infected blood is approximately 0.1 percent. The risk goes
up with prolonged contact and if skin integrity is broken. The
recommendations that follow are based on the summation of the
new data in an attempt to quantify the risks. That is, percutaneous
exposure to blood, especially a deep wound with a visibly bloody
hollow-bore needle, would be in the very high risk category, and
multidrug antiretroviral prophylaxis would be recommended. In
contrast, percutaneous exposure to urine would entail very low
risk, and drug therapy would not be offered.
Why Not Give Drugs to Everyone With Any Exposure?
The answer to this question is not simple. All drugs have risks
of adverse reactions, and little is really known about the use
of multiple AIDS drugs in the healthy patient. Also, the risk
of HIV infection with certain exposures appears to be extremely
low even if no chemoprophylaxis is used (consider the small number
of HCWs who have been infected in the epidemic to date). Therefore,
the risk of drug therapy must be weighed with the likelihood of
HIV seroconversion after exposure. This is obviously a hard issue
to weigh objectively.
In currently recommended doses, ZDV PEP is usually well-tolerated
by HCWs. The toxicity includes gastrointestinal symptoms, fatigue
and headache. Regimes for HCWs who chose to take ZDV in the past
were generally 1,000 mg/day for three to four weeks, while the
current multidrug regime includes ZDV at 200 mg, three times each
day (600 mg/day). It is believed that lamivudine (3TC) and ZDV
together have greater antiretroviral activity than ZDV alone and
may be particularly useful against ZDV-resistant HIV strains with
minimally increased toxicity.
The coming of age of protease inhibitors has led to the use of
triple therapy with indinavir (IDV) as the protease inhibitor
of choice. IDV may be more potent than saquinavir and have fewer
adverse effects than ritonavir. Again, it must be stressed that
there is little to no information about long-term effects in healthy
patients taking these drugs. We do know that in HIV-infected patients,
3TC causes gastrointestinal symptoms and rarely pancreatitis (0.5
percent). IDV also has gastrointestinal symptoms and mild hyperbilirubinemia
(10 percent) and kidney stones (4 percent). During a four-week
course of IDV (suggested prophylactic course), the incidence of
kidney stones was 0.8 percent, according to unpublished data from
Merck Research Laboratories.
Clearly, the potential side effects of these drugs must be considered
if they are taken for PEP, and appropriate monitoring by a knowledgeable
physician must be in place.
Recommendations
The Public Health Service recently published "Recommendations
for Chemoprophylaxis After Occupational Exposure to HIV,"[5]
copies of which will be available through June 7, 1997, from the
CDC National AIDS Clearinghouse, P.O. Box 6003, Rockville, MD
20849-6003; telephone: (800) 458-5231 or (301) 217-0023. The reader
is advised to review the document for more specific details. In
many hospitals, the local infection control staff/committee already
has reviewed this material, and there may be a hotline or a procedure
in place to respond quickly to a needlestick incident.
The recommendations are summarized below:
1. Under certain circumstances (see
Table 1), chemoprophylaxis should be recommended to exposed
workers. The recommendations vary with the degree of risk for
HIV infection. The HCW must understand, however, that the knowledge
of efficacy and toxicity of PEP is limited, and any and all drugs
for PEP may be declined by the exposed HCW.
2. Since ZDV has been used for many years for treatment of HIV,
it has the most data to support its efficacy. However, multidrug
therapy including 3TC and possibly IDV is now recommended because
it is believed to have greater antiretroviral activity (data lacking).
The PEP regimen may vary if the viral strain is known, taking
into account the HIV patient's present drug therapy and the exposed
HCW's tolerance of PEP.
3. PEP should be started within two hours of exposure (if possible).
PEP may not be effective if withheld 24 to 36 hours postexposure,
but this is not certain. However, after a very high risk exposure,
even a delay of one to two weeks may not preclude some benefit
of PEP. The optimal duration of PEP is unknown, but four weeks
of therapy is suggested, if tolerated by the exposed HCW.[4,5]
4. Knowledge about the source patient should help guide PEP decisions.
One basic consideration is the likelihood that the source patient
is in a high-risk group for HIV infection.
5. After occupational exposure to HIV, the HCW should receive
follow-up counseling and medical evaluation. This would include
an HIV test for a baseline and repeat testing for at least six
months (at six weeks, 12 weeks and six months). If PEP is undertaken,
there must be careful medical evaluation and follow-up. Expert
consultation should be sought.
6. An anonymous registry developed by the CDC, Glaxo Wellcome
Inc. and Merck and Co. was developed (July 15, 1996), and HCWs
receiving PEP are encouraged to enroll by calling (888) 737-4448.
If severe toxicity results, the FDA should be informed at (800)
332-1088. As information becomes available, the CDC will update
its recommendations via publications and its Web site, <http://www.cdc.gov>.
The HCW is best advised to seek information through local experts
as well and should be aware of the various sources of new information
in this rapidly changing field of medicine. San Francisco General
Hospital has protocol information readily available for PEP for
HCWs exposed to HIV and can be contacted by e-mail at <protocol@epi-center.ucsf.edu>.
Conclusion
The present data suggest that chemoprophylaxis after occupational
exposure to HIV can be extremely beneficial. While it must be
carefully considered on a case-by-case basis, a multidrug, antiretroviral
regimen for a four-week time period is "recommended"
or "offered" after numerous types of exposure to HIV.
This is a dramatic change from the previous recommendations that
were vague and extremely uncertain. However, the results of a
collaborative, multicenter, multinational, retrospective case-control
study that used data from national surveillance systems have led
the Public Health Service (in consultation with experts from the
CDC, FDA, NIH and other organizations) to recommend PEP in many,
and specific, situations to the HCW exposed to HIV.
This area of medicine is under constant review, and the reader
is urged to consult with local experts when considering PEP. It
is best if a policy is in place locally and the many issues have
been considered by a local infection control committee. Since
PEP should be started ideally within one to two hours after exposure
to HIV, the route to access the appropriate information and drugs
must be clear and procedures in place before an exposure
occurs. There may not be time to consider this topic thoughtfully
and obtain the appropriate drugs after an exposure has occurred.
Of course, prevention of exposure to blood must be the first
line of defense. The recommendations on infection control suggested
by the CDC as well as ASA's specific "Recommendations for
Infection Control for the Practice of Anesthesiology" should
be reviewed and followed. The provisional recommendations of the
Public Health Service concerning chemoprophylaxis are new and
may change. Caution is expressed throughout the document. The
extremely low rate of occupational infection must be kept in mind.
The reader is urged to review the original documents from the
CDC and consider this vital topic so that a truly considered opinion
can be reached.
References:
1. Centers for Disease Control and Prevention.
Pneumocystis pneumonia -- Los Angeles. MMWR. 1981; 30:250-252.
2. Centers for Disease Control and Prevention.
HIV/AIDS surveillance report. MMWR. 1995; 7:2-39.
3. Centers for Disease Control and Prevention.
Case-control study of HIV seroconversion in health-care workers
after percutaneous exposure to HIV-infected blood -- France, United
Kingdom and United States, January 1988 - August 1994. MMWR.
1995; 44:929-933.
4. Gerberding JL. Prophylaxis
for occupational exposure to HIV. Ann Intern Med. 1996;
125:497-501.
5. Centers for Disease Control and Prevention.
Update: Provisional Public Health Service recommendations for
chemoprophylaxis after occupational exposure to HIV. MMWR.
1996; 45(22):468-472.
Samuel C. Hughes, M.D., is Professor of
Anesthesia, San Francisco General Hospital and University of California-San
Francisco School of Medicine, San Francisco, California.
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