| 2006 AIDS HIV UPDATE
Objective |
HIV (human immunodeficiency virus) is the virus that causes AIDS. This virus is passed from one person to another through blood-to-blood and sexual contact. In addition, infected pregnant women can pass HIV to their baby during pregnancy or delivery, as well as through breast-feeding. People with HIV have what is called HIV infection. Most of these people will develop AIDS as a result of their HIV infection.
These body fluids have been proven to spread HIV:
These are additional body fluids that may transmit the virus that health care workers may come into contact with:
What is AIDS? What causes AIDS?
AIDS stands for acquired immunodeficiency syndrome. An HIV-infected person receives a diagnosis of AIDS after developing one of the CDC-defined AIDS indicator illnesses. An HIV-positive person who has not had any serious illnesses also can receive an AIDS diagnosis on the basis of certain blood tests (CD4+ counts).
A positive HIV test result does not mean that a person has AIDS. A diagnosis of AIDS is made by a physician using certain clinical criteria (e.g., AIDS indicator illnesses).
Infection with HIV can weaken the immune system to the point that it has difficulty fighting off certain infections. These types of infections are known as "opportunistic" infections because they take the opportunity a weakened immune system gives to cause illness.
Many of the infections that cause problems or may be life-threatening for people with AIDS are usually controlled by a healthy immune system. The immune system of a person with AIDS is weakened to the point that medical intervention may be necessary to prevent or treat serious illness.
Today there are medical treatments that can slow down the rate at which HIV weakens the immune system. There are other treatments that can prevent or cure some of the illnesses associated with AIDS. As with other diseases, early detection offers more options for treatment and preventative care.
Where did HIV come from?
We do not know. Scientists have different theories about the origin of HIV, but none have been proven. The earliest known case of HIV was from a blood sample collected in 1959 from a man in Kinshasha, Democratic Republic of Congo. (How he became infected is not known.) Genetic analysis of this blood sample suggests that HIV-1 may have stemmed from a single virus in the late 1940s or early 1950s.
We do know that the virus has existed in the United States since at least the mid- to late 1970s. From 1979-1981 rare types of pneumonia, cancer, and other illnesses were being reported by doctors in Los Angeles and New York among a number of gay male patients. These were conditions not usually found in people with healthy immune systems.
In 1982 public health officials began to use the term "acquired immunodeficiency syndrome," or AIDS, to describe the occurrences of opportunistic infections, Kaposi's sarcoma, and Pneumocystis carinii pneumonia in previously healthy men. Formal tracking (surveillance) of AIDS cases began that year in the United States.
The cause of AIDS is a virus that scientists isolated in 1983. The virus was at first named HTLV-III/LAV (human T-cell lymphotropic virus-type III/lymphadenopathy- associated virus) by an international scientific committee. This name was later changed to HIV (human immunodeficiency virus).
US Statistics
AIDS cases and annual rates per 100,000 population, by area and age group, reported through June 1999, United States
How long does it take for HIV to cause AIDS?
Since 1992, scientists have estimated that about half the people with HIV develop AIDS within 10 years after becoming infected. This time varies greatly from person to person and can depend on many factors, including a person's health status and their health-related behaviors.
Today there are medical treatments that can slow down the rate at which HIV weakens the immune system. There are other treatments that can prevent or cure some of the illnesses associated with AIDS, though the treatments do not cure AIDS itself. As with other diseases, early detection offers more options for treatment and preventative health care.
How can I tell if I'm infected with
HIV?
What are the symptoms?
The only way to determine for sure whether you are infected is to be tested for HIV infection. You cannot rely on symptoms to know whether or not you are infected with HIV. Many people who are infected with HIV do not have any symptoms at all for many years.
The following may be warning signs of infection with HIV:
However, no one should assume they are infected if they have any of these symptoms. Each of these symptoms can be related to other illnesses. Again, the only way to determine whether you are infected is to be tested for HIV infection.
Similarly, you cannot rely on symptoms to establish that a person has AIDS. The symptoms of AIDS are similar to the symptoms of many other illnesses. AIDS is a medical diagnosis made by a doctor based on specific criteria established by the CDC.
What are rapid HIV tests?
A rapid test for detecting antibody to HIV is a screening test that produces very quick results, usually in 5 to 30 minutes. In comparison, results from the commonly used HIV antibody screening test, the EIA (enzyme immunoassay), are not available for 1-2 weeks.
The availability of rapid HIV tests may differ from one place to another. The rapid HIV test is considered to be just as accurate as the EIA.
Both the rapid test and the EIA look for the presence of antibodies to HIV. As is true for all screening tests (including the EIA), a reactive rapid HIV test result must be confirmed before a diagnosis of infection can be given.
Using rapid HIV tests to provide results on the day of testing can increase the number of persons who learn their HIV status and also reduce the field efforts necessary to locate and counsel HIV-positive persons who do not return. But providing the result of a single rapid test also has disadvantages, because some reactive test results will be false positives. For counseling and testing programs, the first step in deciding whether to use rapid HIV tests is to determine the potential effects, such as the number of persons who would receive results and the number of false-positive test results at their testing site. These effects can be estimated from the test site's history of the number of persons tested, the number who have tested positive, and the percentage of persons who currently return to receive their HIV test results.
What has been the routine test for HIV antibody testing?
The standard screening test for antibody to HIV is the enzyme immunoasssay (EIA), which is widely used in the United States and around the world. This test requires serum or plasma, so a blood specimen must be drawn from a vein. Because EIA requires specialized equipment, the specimen must be sent to a laboratory, and test results are usually available several days to several weeks later. A negative screening test means a person is not infected with HIV, and does not require further testing. However, a diagnosis of HIV infection cannot be based on a reactive screening test alone. Thus, a reactive EIA is repeated, and repeatedly reactive EIA results are confirmed by a supplemental HIV antibody test --Western blot or immunofluorescence assay (IFA).
Until now, testing required two visits. During the first visit, a client
receives pretest counseling, and blood is drawn for HIV testing. During the
second visit, test results are communicated to the client, additional counseling
is provided, and clients who need them are given referrals for additional
services.
What is rapid HIV testing?
A rapid test for detecting antibody to HIV is a screening test that produces
very quick results, usually in 5 to 30 minutes. Only one rapid HIV test is
licensed by the Food and Drug Administration (FDA) for use in the United
States.
What is the difference between a rapid HIV test and an EIA?
The rapid HIV test is easier to use and produces results more quickly than
the EIA does. The sensitivity and specificity of the rapid HIV test are just as
good as those of the EIA.
Who can be tested with a rapid HIV test?
Rapid HIV testing is suitable for testing any person who would be eligible
for HIV testing by EIA. However, the availability of rapid HIV tests may differ
from one place to another.
Does the rapid HIV test cost more than the EIA?
Yes. The individual kit is more costly then the per-test cost of the EIA. EIA
testing was designed for the automated processing of tests in batches (usually
using a plate that can process 96 specimens at one time.) However, an analysis
done in 1996 by Dr. Paul Farnham and his colleagues at CDC indicated that rapid
HIV testing is more cost-effective than the current EIA-based system, because of
the number of persons who actually learn their results. In other words, although
EIA is less expensive, it is a waste of money to perform lab tests if the person
tested never learns the test result, if two clinic visits are required to get
test results, or if the clinic has to send field staff to locate people for test
results. Since an EIA does not yield immediate results, most people must make a
second visit to learn their results. Experience at publicly funded testing sites
has shown that many persons (26% of those who tested positive for HIV and 33% of
those who tested negative in 1996) do not return for their test results.
Are rapid HIV tests more accurate or less accurate than
EIAs?
The rapid HIV test is just as accurate as an EIA. As is true of all screening
tests (including the EIA), a reactive rapid HIV test result must be confirmed.
Studies in countries where more than one type of rapid HIV test is available
show that specific combinations of two or more different rapid HIV tests can
provide results as reliable as those from an EIA and Western blot or IFA, the
combination that is currently used in the United States. A second rapid HIV test
for persons whose first rapid HIV test is reactive could significantly improve
the predictive value of rapid HIV testing.
What is predictive value?
Predictive value is the calculated probability that a test result predicts
whether a person is truly infected. This calculation produces a number that
counselors can use in explaining HIV test results to their clients. For example,
a higher predictive value means that a reactive test is more likely to indicate
the person is truly infected.
If a person receives a negative rapid HIV test result, is a confirmatory test needed?
A negative antibody test result, whether it is from a rapid HIV test or an
EIA, does not require a confirmatory test. However, a person may have been
tested too soon, before antibodies developed. The average time between infection
and the development of detectable antibodies is 25 days.
Does a negative rapid HIV test result mean that a person has nothing to worry about?
Not necessarily. For most people who are tested, a negative HIV antibody test
result does mean that they are not infected. However, in some cases a person may
have been tested too soon (before antibodies have developed, which requires an
average of 25 days). That is why it is important to assess specific risk
behaviors during counseling, and discuss ways to change risky behaviors.
What is a "reactive" HIV test result?
The term "reactive" is used to describe a test that has detected
the presence of antibodies to HIV. It is recommended that all reactive tests be
repeated immediately, by using the same test. Repeatedly reactive tests are then
further confirmed, by using a different test on the same blood specimen.
After a reactive rapid HIV test result, how long does a person have to wait for the confirmatory test result?
The confirmatory tests are usually sent to a laboratory for processing; results are generally available in 1 to 2 weeks.
If a confirmatory test is still needed, what is the
advantage to sexually transmitted disease (STD) clinics of using rapid HIV
testing?
The advantage to the clinic is that more people will receive their test
results without expensive field visits. Most of the clients at all U.S. publicly
funded testing sites, including STD clinics, test negative for HIV. For these
persons (approximately 2.1 million in 1996), the need to make a second visit
would be eliminated. Of all testing sites, STD clinics have had the lowest
proportion of persons who return for HIV test results. Thus, rapid HIV tests
have the potential to greatly increase the number of persons who learn their
results. In addition, persons who test HIV-positive by the rapid HIV test can be
advised immediately of their screening test result, and counseled about the need
to take precautions to prevent the possibility of transmitting HIV. These
persons of course need to return for their confirmatory test result.
What is the advantage to clients of using rapid HIV
testing?
Interviews with persons being tested indicate that most persons prefer rapid
HIV testing, and most persons who receive a positive HIV screening test result
return on their own to learn the confirmed result (unlike the situation with
current testing, in which many persons learn their test results only as a result
of outreach). This also means that persons who are truly HIV-positive will learn
of their infection sooner. This may help prevent infections that might otherwise
have occurred between the time the person was tested and the time the person
received results (sometimes as long as several weeks.)
Will people who have progressed to the late stages of
AIDS continue to test positive on the rapid HIV tests?
Yes. The progression of HIV disease rarely affects the detection of HIV
antibody.
Can rapid HIV tests be performed on infants?
The result of any HIV antibody test performed on an infant less than 15
months of age may reflect the mother's HIV status, because the antibodies are
transferred from the mother to the baby. Until these antibodies disappear, only
specific virus detection tests can determine the infection status of an infant.
Can clinic staff batch rapid HIV tests?
Yes. Batching, or collecting several specimens before testing all of them at
the same time, can be done. This process can save money for a busy clinic,
because fewer control test kits are required. However, accumulating a sufficient
number of tests for a batch can result in excessive waiting time for the client,
reducing the main benefit of the rapid HIV test: rapid results.
How long does the rapid HIV test take after the lab receives the specimen?
The rapid HIV test usually takes 15 to 30 minutes. The waiting time depends
on how many clients are being tested and whether the clinic is testing
individual samples or batching them. Counseling can be performed while the test
is being done.
What does the counselor tell a client who has a reactive rapid HIV test?
One of the more challenging counseling issues is how to communicate reactive
rapid HIV test results to clients without the benefit of a same-day confirmatory
test result. Counselors should be able to discuss with the client the likelihood
of whether the rapid HIV test result means the client has HIV infection. This
discussion should be based on the prevalence of HIV among persons tested at that
clinic coupled with an assessment of the client's risk behaviors. In clinics
that usually experience a high prevalence of HIV infection among their clients,
a reactive rapid HIV test result is more likely to represent a true infection,
especially in persons who report risk behaviors for HIV. Any person whose rapid
HIV test is reactive should be counseled about the need to take precautions to
prevent any possibility of transmitting HIV infection until their infection
status has been determined by a confirmatory HIV test.
Do you start partner notification and referral services immediately upon receiving a reactive rapid HIV test result, or do you wait for the confirmatory test result?
Partner notification and referral services should not be initiated until the
reactive rapid HIV test result has been confirmed.
Should a physician prescribe antiretroviral treatment for a pregnant woman on the basis of rapid HIV test results (per the PHS Guidelines)?
A negative rapid HIV test of course means that antiretroviral treatment is
not necessary. Deciding what to do about therapy when the rapid HIV test is
reactive is more complicated. If the circumstances are not urgent, it would be
preferable to wait for the confirmatory test result. In other circumstances
(such as a rapid HIV test result for a woman in labor, for whom no other result
is available), physicians should base decisions about antiretroviral treatment
on the predictive value of the preliminary rapid HIV test results and an
assessment of the mother's HIV risk.
Are confirmatory tests necessary for a rapid HIV test result to be considered a diagnosis of HIV infection?
As is true of current EIA antibody procedure, an initial reactive rapid HIV test result should be confirmed by Western blot or IFA. For persons who test positive by confirmatory testing, CDC and the Association of State and Territorial Public Health Laboratory Directors recommend that the test sequence be repeated, by using a different sample, to be absolutely certain of the results.
This test is
Several factors, including temperature and centrifuge speed, can affect test results. Second-generation rapid HIV tests are being developed, and they may be licensed by the FDA in the future.
Second-Generation Rapid HIV Tests
Interpretation is the same as for any HIV screening test. Negative results
from a single rapid HIV test do not require confirmation. Reactive results must
be confirmed by a supplemental HIV antibody test. At this time, confirmation is
done with Western blot or IFA.
Are there other tests available?
The EIA (enzyme immunoassay) is the standard screening test used to detect the presence of antibodies to HIV. The EIA should be used with a confirmatory test such as the Western blot. Tests that detect other signs of HIV are available for special purposes, such as for additional testing of the blood supply and conducting research. Because some tests are expensive or require sophisticated equipment and specialized training, their use is limited. In addition to the EIA, other tests now available include:
How long after a possible exposure should I wait to get tested for HIV?
The tests commonly used to detect HIV infection actually look for antibodies produced by your body to fight HIV. Most people will develop detectable antibodies within 3 months after infection, the average being 25 days. In rare cases, it can take up to 6 months. For this reason, the CDC currently recommends testing 6 months after the last possible exposure (unprotected vaginal, anal, or oral sex or sharing needles). It would be extremely rare to take longer than 6 months to develop detectable antibodies. It is important, during the 6 months between exposure and the test, to protect yourself and others from further possible exposures to HIV.
How is HIV passed from one person to another?
HIV transmission can occur when blood, semen (including pre-seminal fluid, or "pre-cum"), vaginal fluid, or breast milk from an infected person enters the body of an uninfected person.
HIV can enter the body through a vein (e.g., injection drug use), the anus or rectum, the vagina, the penis, the mouth, other mucous membranes (e.g., eyes or inside of the nose), or cuts and sores. Intact, healthy skin is an excellent barrier against HIV and other viruses and bacteria.
These are the most common ways that HIV is transmitted from one person to another:
HIV also can be transmitted through transfusions of infected blood or blood clotting factors. However, since 1985, all donated blood in the United States has been tested for HIV. Therefore, the risk of infection through transfusion of blood or blood products is extremely low. The U.S. blood supply is considered to be among the safest in the world.
Some health-care workers have become infected after being stuck with needles containing HIV-infected blood or, less frequently, after infected blood contact with the worker's open cut or through splashes into the worker's eyes or inside their nose. There has been only one instance of patients being infected by an HIV-infected health care worker. This involved HIV transmission from an infected dentist to six patients.
Are health care workers at risk of getting HIV on the job?
The risk of health care workers getting HIV on the job is very low, especially if they carefully follow universal precautions (i.e., using protective practices and personal protective equipment to prevent HIV and other blood-borne infections). It is important to remember that casual, everyday contact with an HIV-infected person does not expose health care workers or anyone else to HIV. For health care workers on the job, the main risk of HIV transmission is through accidental injuries from needles and other sharp instruments that may be contaminated with the virus. Even this risk is small, however. Scientists estimate that the risk of infection from a needle jab is less than 1 percent, a figure based on the findings of several studies of health care workers who received punctures from HIV-contaminated needles or were otherwise exposed to HIV-contaminated blood.
Can I get HIV from kissing on the cheek?
HIV is not casually transmitted, so kissing on the cheek is very safe. Even if the other person has the virus, your unbroken skin is a good barrier. No one has become infected from such ordinary social contact as dry kisses, hugs, and handshakes.
Can I get HIV from open-mouth kissing?
Open-mouth kissing is considered a very low-risk activity for the transmission of HIV. However, prolonged open-mouth kissing could damage the mouth or lips and allow HIV to pass from an infected person to a partner and then enter the body through cuts or sores in the mouth. Because of this possible risk, the CDC recommends against open-mouth kissing with an infected partner.
One case suggests that a woman became infected with HIV from her sex partner through exposure to contaminated blood during open-mouth kissing. The July 11, 1997, Morbidity and Mortality Weekly Report contains an article on this case.
Can I get HIV from performing oral sex?
Yes, it is possible for you to become infected with HIV through performing oral sex. There have been a few cases of HIV transmission from performing oral sex on a person infected with HIV. While no one knows exactly what the degree of risk is, evidence suggests that the risk is less than that of unprotected anal or vaginal sex.
Blood, semen, pre-seminal fluid, and vaginal fluid all may contain the virus. Cells in the mucous lining of the mouth may carry HIV into the lymph nodes or the bloodstream. The risk increases
If you choose to have oral sex, and your partner is male,
Research has shown the effectiveness of latex condoms used on the penis to prevent the transmission of HIV. Condoms are not risk-free, but they greatly reduce your risk of becoming HIV-infected if your partner has the virus.
If you choose to have oral sex, and your partner is female,
The barrier reduces the risk of blood or vaginal fluids entering your mouth.
Can I get HIV from someone performing oral sex on me?
Yes, it is possible for you to become infected with HIV through receiving oral sex. If your partner has HIV, blood from their mouth may enter the urethra (the opening at the tip of the penis), the vagina, the anus, or directly into the body through small cuts or open sores. While no one knows exactly what the degree of risk is, evidence suggests that the risk is less than that of unprotected anal or vaginal sex.
If you choose to have oral sex,
Research has shown the effectiveness of latex condoms used on the penis for preventing the transmission of HIV. Condoms are not risk-free, but they greatly reduce your risk of becoming HIV-infected if your partner has the virus.
If you choose to have oral sex and you are female,
The barrier reduces the risk of blood entering the body through the vagina.
|
|
Can I get HIV from having vaginal sex?
Yes, it is possible to become infected with HIV through vaginal intercourse. In fact, it is the most common way the virus is transmitted in much of the world. HIV can be found in the blood, semen, pre-seminal fluid, or vaginal fluid of a person infected with the virus. The lining of the vagina can tear and possibly allow HIV to enter the body. Direct absorption of HIV through the mucous membranes that line the vagina also is a possibility.
The male may be at less risk for HIV transmission than the female through vaginal intercourse. However, HIV can enter the body of the male through his urethra (the opening at the tip of the penis) or through small cuts or open sores on the penis.
Risk for HIV infection increases if you or a partner has a sexually transmitted disease (STD).
If you choose to have vaginal intercourse, use a latex condom to help protect both you and your partner from the risk of HIV and other STDs. Studies have shown that latex condoms are very effective, though not perfect, in preventing HIV transmission when used correctly and consistently. If either partner is allergic to latex, plastic (polyurethane) condoms for either the male or female can be used.
Can I get HIV from anal sex?
Yes, it is possible for either sex partner to become infected with HIV during anal sex. HIV can be found in the blood, semen, pre-seminal fluid, or vaginal fluid of a person infected with the virus. In general, the person receiving the semen is at greater risk of getting HIV because the lining of the rectum is thin and may allow the virus to enter the body during anal sex. However, a person who inserts his penis into an infected partner also is at risk because HIV can enter through the urethra (the opening at the tip of the penis) or through small cuts, abrasions, or open sores on the penis.
Having unprotected (without a condom) anal sex is considered to be a very risky behavior. If people choose to have anal sex, they should use a latex condom. Most of the time, condoms work well. However, condoms are more likely to break during anal sex than during vaginal sex. Thus, even with a condom, anal sex can be risky. A person should use a water-based lubricant in addition to the condom to reduce the chances of the condom breaking.
Is there a connection between HIV and other sexually transmitted diseases?
Yes. Having a sexually transmitted disease (STD) can increase a person's risk of becoming infected with HIV, whether the STD causes open sores or breaks in the skin (e.g., syphilis, herpes, chancroid) or does not cause breaks in the skin (e.g., chlamydia, gonorrhea).
If the STD infection causes irritation of the skin, breaks or sores may make it easier for HIV to enter the body during sexual contact. Even when the STD causes no breaks or open sores, the infection can stimulate an immune response in the genital area that can make HIV transmission more likely.
In addition, if an HIV-infected person also is infected with another STD, that person is three to five times more likely than other HIV-infected persons to transmit HIV through sexual contact.
How effective are latex condoms in preventing HIV?
Studies have shown that latex condoms are highly effective in preventing HIV transmission when used consistently and correctly. These studies looked at uninfected people considered to be at very high risk of infection because they were involved in sexual relationships with HIV-infected people. The studies found that even with repeated sexual contact, 98-100 percent of those people who used latex condoms correctly and consistently did not become infected.
Why is injecting drugs a risk for HIV?
At the start of every intravenous injection, blood is introduced into needles and syringes. HIV can be found in the blood of a person infected with the virus. The reuse of a blood-contaminated needle or syringe by another drug injector (sometimes called "direct syringe sharing") carries a high risk of HIV transmission because infected blood can be injected directly into the bloodstream.
In addition, sharing drug equipment (or "works") can be a risk for spreading HIV. Infected blood can be introduced into drug solutions by
"Street sellers" of syringes may repackage used syringes and sell them as sterile syringes. For this reason, people who continue to inject drugs should obtain syringes from reliable sources of sterile syringes, such as pharmacies. It is important to know that sharing a needle or syringe for any use, including skin popping and injecting steroids, can put one at risk for HIV and other blood-borne infections.
How can people who use injection drugs reduce their risk for HIV infection?
The CDC recommends that people who inject drugs should be regularly counseled to
For injection drug users who cannot or will not stop injecting drugs, the following steps may be taken to reduce personal and public health risks:
If new, sterile syringes and other drug preparation and injection equipment are not available, then previously used equipment should be boiled in water or disinfected with bleach before reuse.
Can I get HIV from getting a tattoo or through body piercing?
A risk of HIV transmission does exist if instruments contaminated with blood are either not sterilized or disinfected or are used inappropriately between clients. CDC recommends that instruments that are intended to penetrate the skin be used once, then disposed of or thoroughly cleaned and sterilized.
Personal service workers who do tattooing or body piercing should be educated about how HIV is transmitted and take precautions to prevent transmission of HIV and other blood-borne infections in their settings. If you are considering getting a tattoo or having your body pierced, ask staff at the establishment what procedures they use to prevent the spread of HIV and other blood-borne infections, such as hepatitis B virus. You also may call the local health department to find out what sterilization procedures are in place in the local area for these types of establishments.
Are patients in a dentist's or doctor's office at risk of getting HIV?
Although HIV transmission is possible in health care settings, it is extremely rare. Medical experts emphasize that the careful practice of infection control procedures, including universal precautions, protects patients as well as health care providers from possible HIV infection in medical and dental offices.
In 1990, the CDC reported on an HIV-infected dentist in Florida who apparently infected some of his patients while doing dental work. Studies of viral DNA sequences linked the dentist to six of his patients who were also HIV-infected. The CDC has as yet been unable to establish how the transmission took place.
Further studies of more than 22,000 patients of 63 health care providers who were HIV-infected have found no further evidence of transmission from provider to patient in health care settings.
Should I be concerned about getting infected with HIV while playing sports?
There are no documented cases of HIV being transmitted during participation in sports. The very low risk of transmission during sports participation would involve sports with direct body contact in which bleeding might be expected to occur.
If someone is bleeding, their participation in the sport should be interrupted until the wound stops bleeding and is both antiseptically cleaned and securely bandaged. There is no risk of HIV transmission through sports activities where bleeding does not occur
Can I get HIV from casual contact (shaking hands, hugging, using a toilet, drinking from the same glass, or the sneezing and coughing of an infected person)?
No. HIV is not transmitted by day-to-day contact in the workplace, schools, or social settings. HIV is not transmitted through shaking hands, hugging, or a casual kiss. You cannot become infected from a toilet seat, a drinking fountain, a door knob, dishes, drinking glasses, food, or pets.
A small number of cases of transmission have been reported in which a person became infected with HIV as a result of contact with blood or other body secretions from an HIV-infected person in the household. Although contact with blood and other body substances can occur in households, transmission of HIV is rare in this setting. However, persons infected with HIV and persons providing home care for those who are HIV-infected should be fully educated and trained regarding appropriate infection-control techniques.
HIV is not an airborne or food-borne virus, and it does not live long outside the body. HIV can be found in the blood, semen, or vaginal fluid of an infected person. The three main ways HIV is transmitted are
Can I get infected with HIV from mosquitoes?
No. From the start of the HIV epidemic there has been concern about HIV transmission of the virus by biting and bloodsucking insects, such as mosquitoes. However, studies conducted by the CDC and elsewhere have shown no evidence of HIV transmission through mosquitoes or any other insects -- even in areas where there are many cases of AIDS and large populations of mosquitoes. Lack of such outbreaks, despite intense efforts to detect them, supports the conclusion that HIV is not transmitted by insects.
The results of experiments and observations of insect biting behavior indicate that when an insect bites a person, it does not inject its own or a previously bitten person's or animal's blood into the next person bitten. Rather, it injects saliva, which acts as a lubricant so the insect can feed efficiently. Diseases such as yellow fever and malaria are transmitted through the saliva of specific species of mosquitoes. However, HIV lives for only a short time inside an insect and, unlike organisms that are transmitted via insect bites, HIV does not reproduce (and does not survive) in insects. Thus, even if the virus enters a mosquito or another insect, the insect does not become infected and cannot transmit HIV to the next human it bites.
There also is no reason to fear that a mosquito or other insect could transmit HIV from one person to another through HIV-infected blood left on its mouth parts. Several reasons help explain why this is so. First, infected people do not have constantly high levels of HIV in their blood streams. Second, insect mouth parts retain only very small amounts of blood on their surfaces. Finally, scientists who study insects have determined that biting insects normally do not travel from one person to the next immediately after ingesting blood. Rather, they fly to a resting place to digest the blood meal.
Informed Consent
In many states no medical professional can perform an HIV test without first obtaining informed consent. Consent includes an explanation of the purpose and limitations of the test, meaning of test results, measures for the prevention of exposure to and transmission of HIV, the benefits of partner notification, the availability of health care services, and confidentiality of test results.
The patient should be pre-test counseled and post test counseled by a Certified HIV Counselor or licensed physician. When a person is incompetent or under the age of majority, informed consent must be obtained from a legal guardian or other authorized person.
The following minors should be treated as adults:
Exceptions to HIV Informed Consent
An essential component of efforts to prevent new human immunodeficiency virus (HIV) infections in the United States is the use of voluntary HIV counseling and testing by persons at risk for HIV, especially members of underserved populations (1). To increase the number of persons at risk for HIV who receive voluntary HIV counseling and testing services, barriers to these services must be identified and removed. The stigmatization of persons infected with HIV and the groups most affected by HIV, including men who have sex with men and illicit drug users, is a barrier to testing (2,3). Measuring public attitudes and knowledge about HIV transmission to determine the prevalence and the correlates of stigmatizing attitudes is important for guiding efforts to remove barriers to HIV prevention. This report describes the results of a national public opinion survey conducted through the Internet to measure indicators of HIV-related stigma and knowledge of HIV transmission. The findings indicate that most persons do not have stigmatizing views.
During August--September 2000, Research Triangle Institute conducted an Internet-based, household survey in a sample of 7493 adults aged >18 years. The sample was proportionately selected from a nationally representative panel of approximately 45,000 households. To establish the panel, a sample of U.S. households obtained through random-digit--dialed telephone sampling was offered Internet access and equipment in exchange for participation in weekly surveys. Surveys were conducted using a standard television set connected to the Internet, and responses were entered using a remote control. A module on HIV-related stigma and knowledge of transmission was included in a larger survey on health and aging. This analysis is based on 5641 respondents (75.3%) who answered the question on HIV stigma.
The survey included one question that was considered a proxy indicator for a stigmatizing attitude. Participants were identified who strongly agreed or agreed with the statement "People who got AIDS [acquired immunodeficiency syndrome] through sex or drug use have gotten what they deserve." Although this question addresses only one element of HIV/AIDS stigma, for this report, these answers were considered a "stigmatizing" response. Two questions concerned knowledge about HIV transmission. Persons who responded that it was very unlikely or impossible to become infected through sharing a glass or being coughed or sneezed on were considered informed; those who stated that it was very likely, somewhat likely, or somewhat unlikely were classified as misinformed. Percentage estimates were weighted to provide representative estimates, and confidence intervals (CIs) and p-values were computed using SUDAAN.
Among the 5641 respondents, 40.2% (95% CI=38.8%--41.6%) responded that HIV transmission could occur (i.e., it was very likely, somewhat likely, or somewhat unlikely) through sharing a glass, and 41.1% (CI=39.7%--42.5%) responded that it could occur from being coughed or sneezed on by an HIV-infected person. A total of 18.7% responded that persons who acquired AIDS through sex or drug use have gotten what they deserve. Stigmatizing responses were more common among men (21.5%), whites (20.8%), persons aged >55 years (30.0%), those with only a high school education (22.1%), those with an income <$30,000 (23.4%), and those in poorer health compared with others (23.6%) (Table 1). For both transmission questions, approximately 25% of those who were misinformed gave stigmatizing responses, compared with approximately 14% who were informed (p<0.05).
Reported by: DA Lentine, JC Hersey, VG Iannacchione, GH Laird, K McClamroch, L Thalji, Research Triangle Institute, Research Triangle Park, North Carolina. Prevention Informatics Office, Office of the Director; Behavioral Intervention Research Br, Div of HIV/AIDS Prevention--Intervention Research and Support, National Center for HIV, STD, and TB Prevention, CDC.
The findings in this report suggest that most U.S. adults do not hold stigmatizing views about persons with HIV infection or AIDS. However, a substantial minority gave a response that suggests they may have stigmatizing attitudes about persons with HIV. The smallest proportion of respondents who gave this response was black, the racial/ethnic group with the highest rates of AIDS in the United States. Significantly more of the respondents who were misinformed about HIV transmission gave a stigmatizing response, suggesting that increasing understanding about behaviors related to HIV transmission may result in lower levels of stigmatizing beliefs about infected persons. However, many other factors are probably related to stigma.
Early HIV diagnosis and entry into health care have both individual and societal benefits: improved health and productivity, reduced hospitalization costs, and decreased transmission from persons who do not know their HIV status (1). Because most HIV-infected persons probably will adopt safer sexual behaviors after the diagnosis of HIV infection (4,5), increasing the number of infected persons who know their serostatus is an important prevention goal. However, HIV-infected persons who fear being stigmatized are typically reluctant to acknowledge risk behaviors, avoid seeking prevention information, and may experience real or perceived barriers to prevention and other health-care services (2,3). Therefore, public health measures that encourage access to HIV testing by reducing stigma (e.g., social marketing campaigns targeted to high risk, stigmatized populations; sexuality and cultural sensitivity training for health-care providers; and anonymous testing opportunities) strengthen HIV-prevention efforts.
The findings in this report are subject to at least two limitations. First, the results are based on only one question about stigma, which comprises a range of attitudes, beliefs, and behaviors. Second, the survey did not include persons who do not own a telephone, persons in institutions, the transient or homeless, and those living on military installations. Despite these limitations, the sampling methods eliminated the main bias in earlier Internet samples (i.e., a lack of universal access to the Internet) while preserving the advantages of Internet surveys. In addition, the panel closely matched the overall U.S. population with respect to age, race/ethnicity, sex, education, and income.
Stigma includes prejudice and active discrimination directed toward persons either perceived to be or actually infected with HIV and the social groups and persons with whom they are associated (3). Overcoming stigma is an important step in persons seeking to know their HIV status. Measurements such as those conducted in this study help to direct and assess efforts to overcome these barriers.
Objectives:
This report updates and consolidates all previous PHS recommendations for the management of health-care workers (HCWs) who have occupational exposure to blood and other body fluids that may contain human immunodeficiency virus (HIV); it includes recommendations for HIV postexposure prophylaxis (PEP) and discusses the scientific rationale for PEP. The decision to recommend HIV postexposure prophylaxis must take into account the nature of the exposure (e.g., needlestick or potentially infectious fluid that comes in contact with a mucous membrane) and the amount of blood or body fluid involved in the exposure. Other considerations include pregnancy in the HCW and exposure to virus known or suspected to be resistant to antiretroviral drugs. Assessments of the risk for infection resulting from the exposure and of the infectivity of the exposure source are key determinants of offering PEP. Systems should be in place for the timely evaluation and management of exposed HCWs and for consultation with experts in the treatment of HIV when using PEP.
Recommendations for PEP have been modified to include a basic 4-week regimen of two drugs (zidovudine and lamivudine) for most HIV exposures and an expanded regimen that includes the addition of a protease inhibitor (indinavir or nelfinavir) for HIV exposures that pose an increased risk for transmission or where resistance to one or more of the antiretroviral agents recommended for PEP is known or suspected. An algorithm is provided to guide clinicians and exposed health-care workers in deciding when to consider PEP.
Occupational exposures should be considered urgent medical concerns to ensure timely administration of PEP. Health-care organizations should have protocols that promote prompt reporting and facilitate access to postexposure care. Enrollment of HCWs in registries designed to assess side effects in HCWs who take PEP is encouraged.
INTRODUCTION
Although preventing blood exposures is the primary means of preventing occupationally acquired human immunodeficiency virus (HIV) infection, appropriate postexposure management is an important element of workplace safety. In January 1990, CDC issued a statement on the management of HIV exposures that included considerations for zidovudine (ZDV) use for postexposure prophylaxis (PEP) (1). At that time, data were insufficient to assess the efficacy of ZDV as a prophylactic agent in humans or the toxicity of this drug in persons not infected with HIV. Although there are still only limited data to assess safety and efficacy, additional information is now available that is relevant to this issue.
In December 1995, CDC published a brief report of a retrospective case-control study of health-care workers (HCWs) from France, the United Kingdom, and the United States exposed percutaneously to HIV; the study identified risk factors for HIV transmission and documented that the use of ZDV was associated with a decrease in the risk for HIV seroconversion (2). This information, along with data on ZDV efficacy in preventing perinatal transmission (3) and evidence that PEP prevented or ameliorated retroviral infection in some studies in animals (4), prompted a Public Health Service (PHS) interagency working group *, with expert consultation (5), in June 1996 to issue provisional recommendations for PEP for HCWs after occupational HIV exposure (6).
Since the provisional recommendations were released, several new antiretroviral drugs have been approved by the Food and Drug Administration (FDA), and more information is available about the use and safety of antiretroviral agents in exposed HCWs (7-10). In addition, questions have been raised about the use of chemoprophylaxis in situations not fully addressed in the 1996 recommendations, including when not to offer PEP, what to do when the source of exposure or the HIV status of the source person is unknown, how to approach PEP in HCWs who are or may be pregnant, and considerations for PEP regimens when the source person's virus is known or suspected to be resistant to one or more of the antiretroviral agents recommended for PEP.
In May 1997, a meeting of expert consultants, convened by CDC to consider the new information, prompted a PHS interagency working group ** decision to issue updated recommendations. This document addresses the management of occupational exposure to HIV, including guidance in assessing and treating exposed HCWs, updates previous recommendations for occupational postexposure chemoprophylaxis, and updates and replaces all previous PHS guidelines and recommendations for occupational HIV exposure management for HCWs. Included in this document is an algorithm to guide decisions regarding the use of PEP for HIV exposures. The algorithm and these recommendations together address most issues that may be encountered during postexposure follow-up. As relevant information becomes available, updates of these recommendations will be published. Recommendations for nonoccupational (e.g., sexual or pediatric) exposures are not addressed in these guidelines.
DEFINITIONS OF HEALTH-CARE WORKERS AND EXPOSURE
In this report, "health-care worker" (HCW) is defined as any person (e.g., an employee, student, contractor, attending clinician, public-safety worker, or volunteer) whose activities involve contact with patients or with blood or other body fluids from patients in a health-care or laboratory setting. An "exposure" that may place an HCW at risk for HIV infection and therefore requires consideration of PEP is defined as a percutaneous injury (e.g., a needlestick or cut with a sharp object), contact of mucous membrane or nonintact skin (e.g., when the exposed skin is chapped, abraded, or afflicted with dermatitis), or contact with intact skin when the duration of contact is prolonged (i.e., several minutes or more) or involves an extensive area, with blood, tissue, or other body fluids. Body fluids include a) semen, vaginal secretions, or other body fluids contaminated with visible blood that have been implicated in the transmission of HIV infection (11,12); and b) cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids, which have an undetermined risk for transmitting HIV (11). In addition, any direct contact (i.e., without barrier protection) to concentrated HIV in a research laboratory or production facility is considered an "exposure" that requires clinical evaluation and consideration of the need for PEP.
Although one nonoccupational episode of HIV transmission has been attributed to contact with blood-contaminated saliva (13), this incident involved intimate kissing between sexual partners and is not similar to contact with saliva that may occur during the provision of health-care services. Therefore, in the absence of visible blood in the saliva, exposure to saliva from a person infected with HIV is not considered a risk for HIV transmission; also, exposure to tears, sweat, or nonbloody urine or feces does not require postexposure follow-up. ***
Human breast milk has been implicated in perinatal transmission of HIV. However, occupational exposure to human breast milk has not been implicated in HIV transmission to HCWs. Moreover, the contact HCWs may have with human breast milk is quite different from perinatal exposure and does not require postexposure follow-up.
BACKGROUND
The rationale is provided here for the postexposure management and prophylaxis recommendations given at the end of the document. Additional details concerning the risk for occupational HIV transmission to HCWs and management of occupational HIV exposures are available elsewhere (16-18).
Risk for Occupational Transmission of HIV to HCWs
Prospective studies of HCWs have estimated that the average risk for HIV transmission after a percutaneous exposure to HIV-infected blood is approximately 0.3% (95% confidence interval {CI}=0.2%-0.5%) (16) and after a mucous membrane exposure is 0.09% (95% CI=0.006%-0.5%) (19). Although episodes of HIV transmission after skin exposure have been documented (20), the average risk for transmission by this route has not been precisely quantified because no HCWs enrolled in prospective studies have seroconverted after an isolated skin exposure. The risk for transmission is estimated to be less than the risk for mucous membrane exposures (21). The risk for transmission after exposure to fluids or tissues other than HIV-infected blood also has not been quantified.
As of June 1997, CDC has received reports of 52 U.S. HCWs with documented HIV seroconversion temporally associated with an occupational HIV exposure. An additional 114 episodes in HCWs are considered possible occupational HIV transmissions; these workers reported that their infection was occupationally acquired and no other risk for HIV infection was identified, but transmission of infection after a specific exposure was not documented (22). Of the 52 documented episodes, 47 HCWs were exposed to HIV-infected blood, one to a visibly bloody body fluid, one to an unspecified fluid, and three to concentrated virus in a laboratory. Forty-five exposures were percutaneous, and five were mucocutaneous; one HCW had both a percutaneous and a mucocutaneous exposure. The route of exposure for one person exposed to concentrated virus is uncertain. Of the percutaneous exposures, the objects involved included a hollow-bore needle (41), a broken glass vial (two), a scalpel (one), and an unknown sharp object (one) (CDC, unpublished data, 1998).
Epidemiologic and laboratory studies suggest that several factors may affect the risk for HIV transmission after an occupational exposure. The one retrospective case-control study of HCWs who had percutaneous exposure to HIV found that the risk for HIV transmission was increased with exposure to a larger quantity of blood from the source patient as indicated by a) a device visibly contaminated with the patient's blood, b) a procedure that involved a needle placed directly in a vein or artery, or c) a deep injury (23). (A laboratory study that demonstrated that more blood is transferred by deeper injuries and hollow-bore needles lends further support for the observed variation in risk related to blood quantity {24}). The risk also was increased for exposure to blood from source patients with terminal illness, possibly reflecting either the higher titer of HIV in blood late in the course of AIDS or other factors (e.g., the presence of syncytia-inducing strains of HIV). It was estimated that the risk for HIV transmission from exposures that involve a larger volume of blood, particularly when the source patient's viral load is probably high, exceeds the average risk of 0.3% (23).
The utility of viral load measurements from a source patient as a surrogate for estimating the viral titer for assessing transmission risk is not known. Plasma viral load measurement (e.g., HIV RNA) reflects only the level of cell-free virus in the peripheral blood. This measurement does not reflect the level of cell-associated virus in the peripheral blood or the level of virus in other body compartments (e.g., lymphatic tissue). Although a lower viral load, or results that are below the limits of viral quantification, in the peripheral blood probably indicates a lower titer exposure, it does not rule out the possibility of transmission; HIV transmission from persons with a plasma viral load below the limits of viral quantification (based on the assay used at the time) has been reported in instances of mother-to-infant transmission (25,26) and in one HCW seroconversion (J.L. Gerberding, San Francisco General Hospital, unpublished data, May 1997).
There is some evidence that host defenses also may influence the risk for HIV infection. In one small study, HIV-exposed but uninfected HCWs demonstrated an HIV-specific cytotoxic T-lymphocyte (CTL) response when peripheral blood mononuclear cells were stimulated in vitro with HIV mitogens (27). Similar CTL responses have been observed in other populations with repeated HIV exposure without resulting infection (28-33). Among several possible explanations for this observation, one is that the host immune response sometimes may be able to prevent establishment of HIV infection after a percutaneous exposure; another is that the CTL response simply may be a marker for exposure.
HIV Seroconversion in HCWs
Data on the timing and clinical characteristics of seroconversion in HIV-exposed HCWs are limited by the infrequency of infection following occupational exposure, variations in postexposure testing intervals, and differences over time in the sensitivity of HIV-antibody testing methods. Among the HCWs with documented seroconversions reported to CDC for whom data are available, 81% experienced a syndrome compatible with primary HIV infection a median of 25 days after exposure (CDC, unpublished data, 1998). In a recent analysis of 51 seroconversions in HCWs, the estimated median interval from exposure to seroconversion was 46 days (mean: 65 days); an estimated 95% seroconverted within 6 months after the exposure (34). These data suggest that the time course of HIV seroconversion in HCWs is similar to that in other persons who have acquired HIV through nonoccupational modes of transmission (35).
Three instances of delayed HIV seroconversion occurring in HCWs have been reported; in these instances, the HCWs tested negative for HIV antibodies greater than 6 months postexposure but were seropositive within 12 months after the exposure (36,37; J.L. Gerberding, San Francisco General Hospital, unpublished data, May 1997). DNA sequencing confirmed the source of infection in one instance. Two of the delayed seroconversions were associated with simultaneous exposure to hepatitis C virus (HCV) (37; J.L. Gerberding, San Francisco General Hospital, unpublished data, May 1997). In one case, co-infection was associated with a rapidly fatal HCV disease course (37); however, it is not known whether HCV directly influences the risk for or course of HIV infection or is a marker for other exposure-related factors.
Rationale for PEP
Considerations that influence the rationale and recommendations for PEP include the pathogenesis of HIV infection, particularly the time course of early infection; the biologic plausibility that infection can be prevented or ameliorated by using antiretroviral drugs and direct or indirect evidence of the efficacy of specific agents used for prophylaxis; and the risk/benefit of PEP to exposed HCWs. The following discussion considers each of these issues.
Role of Pathogenesis in Considering Antiretroviral Prophylaxis
Information about primary HIV infection indicates that systemic infection does not occur immediately, leaving a brief "window of opportunity" during which postexposure antiretroviral intervention may modify viral replication. Data from studies in animal models and in vitro tissue studies suggest that dendritic cells in the mucosa and skin are the initial targets of HIV infection or capture and have an important role in initiating HIV infection of CD4+ T-cells in regional lymph nodes (38). In a primate model of simian immunodeficiency virus (SIV) infection, infection of dendritic-like cells occurred at the site of inoculation during the first 24 hours following mucosal exposure to cell-free virus. During the subsequent 24-48 hours, migration of these cells to regional lymph nodes occurred, and virus was detectable in the peripheral blood within 5 days (39). HIV replication is rapid (generation time: 2.5 days) and results in bursts of up to 5,000 viral particles from each replicating cell (40; M.S. Saag, University of Alabama, personal communication, September 1997). The exponential increase in viral burden continues unless controlled by the immune system or other mechanisms (e.g., exhaustion of available target CD4+ T-cells). Theoretically, initiation of antiretroviral PEP soon after exposure may prevent or inhibit systemic infection by limiting the proliferation of virus in the initial target cells or lymph nodes.
Efficacy of Antiretrovirals for PEP
Studies in animals and humans provide direct and indirect evidence of the efficacy of antiretroviral drugs as agents for postexposure prophylaxis. In human studies and in most animal studies, ZDV was the antiretroviral agent used for prophylaxis (26,41-54). However, in more recent animal studies, newer agents also have been reported to be effective (55,56).
Data from animal studies have been difficult to interpret, in part because of problems identifying a comparable animal model for humans. Most studies use a higher inoculum for exposure than would be expected in needlestick injuries. Among the animal studies, differences in controlled variables (e.g., choice of viral strain {based on the animal model used}, inoculum size, route of inoculation, time of prophylaxis initiation, and drug regimen) make attempts to apply these results to humans difficult. In the animal studies that showed efficacy of pre-exposure and/or postexposure prophylaxis, reported outcomes (4,57) have included
suppression of viremia or delayed antigenemia (41-47); b) drug-facilitated vaccine-type response (i.e., chemoprophylaxis sufficiently inhibited viral replication to permit formation of a long-lasting, protective cellular immune response) (48-56); and c) definitive prevention of infection (i.e., chemoprophylactic efficacy) (41,52-54). More recent refinements in methodology have enabled studies more relevant to humans; in particular, the viral inocula used in animal studies have been reduced to levels more analogous to human exposures (54,56). The results of these studies provide additional evidence of postexposure chemoprophylactic efficacy.
In studies of HIV-2 or SIV in nonhuman primates in which ZDV or 3'-fluorothymidine was used, suppression or delay of antigenemia was the most common outcome; prevention of infection was infrequent (43,52,58-60). However, two other antiretroviral agents, 2',3'-dideoxy-3'-hydroxymethyl cytidine (BEA-005) and (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA), used to study PEP in primates have been more effective in preventing infection. When PMPA was administered 48 hours before, 4 hours after, or 24 hours after intravenous SIV inoculation to long-tailed macaques, a 4-week regimen prevented infection in all treated animals (55). A 3-day regimen of BEA-005 prevented SIV infection in 12 of 12 pigtailed macaques when administered 1-8 hours after intravenous inoculation; infection also was prevented in four of four animals that received 3 days of BEA-005 within 10 minutes after HIV-2 inoculation (56).
Animal studies have demonstrated that early initiation of PEP and small inoculum size are correlates of successful PEP. ZDV initiated 1 hour or 24 hours after intravenous exposure to a rapidly lethal variant of SIV in pigtailed macaques prevented infection in one of three animals and modified SIV disease in three of six animals, respectively; PEP initiated at 72 hours had no effect (54). In macaques administered ZDV or BEA-005 1 to 72 hours after SIV intravenous challenge, earlier initiation of PEP was correlated with delayed onset and peak of antigenemia, decreased duration of antigenemia, and reduction in SIV serum titer; the most potent effect was evident when PEP was initiated within 8 hours of exposure (43,56). Studies in primates and murine and feline animal models have demonstrated that larger inocula decrease prophylactic efficacy (47,48,53,60). In addition, delaying initiation, shortening the duration, or decreasing the antiretroviral dose of PEP, individually or in combination, decreased prophylactic efficacy (42,43,45,47,50,55).
There is little information with which to assess the efficacy of PEP in humans. Seroconversion is infrequent after an occupational exposure to HIV-infected blood; therefore a prospective trial would need to enroll many thousands of exposed HCWs to achieve the statistical power necessary to directly demonstrate PEP efficacy. During 1987-1989, the Burroughs-Wellcome Company sponsored a prospective placebo-controlled clinical trial among HCWs to evaluate 6 weeks of ZDV prophylaxis; however, this trial was terminated prematurely because of low enrollment (61). Because of current indirect evidence of PEP efficacy, it is unlikely that a placebo-controlled trial in HCWs would ever be feasible.
In the retrospective case-control study of HCWs, after controlling for other risk factors for HIV transmission, the risk for HIV infection among HCWs who used ZDV as PEP was reduced by approximately 81% (95% CI=43%-94%) (23). In addition, in a randomized, controlled, prospective trial (AIDS Clinical Trial Group {ACTG} protocol 076) in which ZDV was administered to HIV-infected pregnant women and their infants, the administration of ZDV during pregnancy, labor, and delivery and to the infant reduced transmission by 67% (3). Only 9%-17% (depending on the assay used) of the protective effect of ZDV was explained by reduction of the HIV titer in the maternal blood, suggesting that ZDV prophylaxis in part involves a mechanism other than the reduction of maternal viral burden (26).
The limitations of all of these studies must be considered when reviewing evidence of PEP efficacy. The extent to which data from animal studies can be extrapolated to humans is largely unknown, and the exposure route for mother-to-infant HIV transmission is not similar to occupational exposures; therefore these findings may not reflect a similar mechanism of ZDV prophylaxis in HCWs. Although the results of the retrospective case-control study of HCWs suggest PEP efficacy, the limitations of that study include the small number of cases studied and the use of cases and controls from different cohorts.
Failure of ZDV PEP to prevent HIV infection in HCWs has been reported in at least 14 instances (62-64; G. Ippolito, AIDS Reference Center, Rome, Italy, and J. Heptonstall, Communicable Disease Surveillance Center, London, United Kingdom, personal communication, 1997). Although eight of the 13 source patients had taken ZDV, laboratory assessment for ZDV resistance of the virus from the source patient was performed in only three instances, two of which demonstrated reduced susceptibility to ZDV. In addition to possible exposure to a ZDV-resistant strain of HIV, other factors that may have contributed to the apparent failures in these instances may include a high titer and/or large inoculum exposure, delayed initiation and/or short duration of PEP, and possible factors related to the host (e.g., cellular immune system responsiveness) and/or to the source patient's virus (e.g., presence of syncytia-forming strains) (62).
Antiretroviral Agents for PEP
Several antiretroviral agents from at least three classes of drugs are available for the treatment of HIV disease. These include the nucleoside analogue reverse transcriptase inhibitors (NRTIs), nonnuceloside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) (See Appendix). Among these drugs, ZDV (an NRTI) is the only agent shown to prevent HIV transmission in humans (2,3). Although there are theoretical concerns that the increased prevalence of resistance to ZDV may diminish its utility for PEP (65), no data are available to assess whether this is a factor for consideration. Clinical data from the ACTG protocol 076 study documented that despite genotypic evidence of maternal ZDV resistance, ZDV prevented perinatal transmission (66). Thus, based on the available information, it is still reasonable that ZDV should continue to be the first drug of choice for PEP regimens.
There are no data to directly support the addition of other antiretroviral drugs to ZDV to enhance the effectiveness of the PEP regimen. However, in HIV-infected patients, combination regimens have proved superior to monotherapy regimens in reducing HIV viral load (67,68). Thus, theoretically a combination of drugs with activity at different stages in the viral replication cycle (e.g., NRTIs with a PI) could offer an additive preventive effect in PEP, particularly for occupational exposures that pose an increased risk for transmission.
Determining which agents and how many agents to use or when to alter a PEP regimen is largely empiric. Guidelines for the treatment of early HIV infection recommend the use of three drugs (two NRTIs and a PI) (69); however, the applicability of these recommendations to PEP remains unknown. In addition, the routine use of three drugs for all occupational HIV exposures may not be needed. Although the use of a highly potent regimen can be justified for exposures that pose an increased risk for transmission, it is uncertain whether the potential additional toxicity of a third drug is justified for lower-risk exposures. For this reason, the recommendations at the end of this report provide guidance for two- and three-drug PEP regimens that are based on the level of risk for HIV transmission represented by the exposure.
NRTIs that can be considered for use with ZDV for PEP are lamivudine (3TC), didanosine (ddI), and zalcitabine, each of which has been included in recommended regimens that include ZDV (69). In previous CDC recommendations, 3TC was recommended as a second agent for PEP based on greater antiretroviral activity of the ZDV/3TC combination and its activity against many ZDV-resistant HIV strains without substantially increased toxicity (6). Also, data suggest that ZDV-resistant mutations develop more slowly in patients receiving the ZDV/3TC combination than those receiving ZDV alone (70), and in vitro studies indicate that the mutation associated with 3TC resistance may be associated with reversal of ZDV phenotypic resistance (71). No additional information has emerged to warrant altering the original recommendation of 3TC as the second agent for PEP. In addition, because ZDV and 3TC are available in a combination formulation (CombivirTM, manufactured by Glaxo Wellcome, Inc., Research Triangle Park, NC), the use of 3TC may be more convenient for HCWs. However, individual clinicians may prefer other NRTIs or combinations of other antiretroviral agents based on local knowledge and experience in treating HIV infection and disease.
The addition of a PI as a third drug for PEP following high-risk exposures is based on the site of activity in the replication cycle (i.e., after viral integration has occurred) and demonstrated effectiveness in reducing viral burden. Previously, indinavir (IDV) was recommended as the PI for PEP because of its increased bioavailability when compared with saquinavir and its more favorable immediate toxicity profile compared with ritonavir (72). In addition, requirements for dose escalation when initiating ritonavir make it less practical for use in PEP. Since the 1996 PEP recommendations were published, nelfinavir (NEL) was approved for use by FDA and is now included in regimens recommended for the treatment of primary HIV infection (69). Also, FDA recently approved a soft-gel formulation of saquinavir (FortovaseTM, manufactured by Hoffmann-LaRoche, Inc., Nutley, New Jersey) that has improved bioavailability relative to its hard-gel formulation (InviraseTM, manufactured by Hoffmann-LaRoche, Inc.). However, the recommended dose of soft-gel saquinavir (1200 mg three times a day) is twice that of the hard-gel formulation (600 mg three times a day) and necessitates taking 18 pills a day, a factor that may influence HCW compliance if used for PEP. Based on these considerations, either IDV or NEL is recommended as first choice for inclusion in an expanded PEP regimen. If saquinavir is preferred by the prescribing physician, the soft-gel formulation (FortovaseTM) should be used. Also, differences in the side effects associated with IDV and NEL, discussed below, may influence which of these agents is selected in a specific situation.
The NNRTIs (i.e., nevirapine and delavirdine) have not been included in these recommended regimens for PEP. As a class of antiretroviral agents, the NNRTIs are fast-acting and very potent, making them appealing in concept for PEP. In addition, there is some evidence of prophylactic efficacy (73). However, concerns about side effects and the availability of alternative agents argue against routinely using this class of drugs for initial PEP, although with expert consultation, an NNRTI might be considered.
Side Effects and Toxicity of Antiretroviral Agents
An important goal of PEP is to encourage and facilitate compliance with a 4-week PEP regimen. Therefore, the toxicity profile of antiretroviral agents, including the frequency, severity, duration, and reversibility of side effects, is a relevant consideration. All of the antiretroviral agents have been associated with side effects (See Appendix). However, studies of adverse events have been reported primarily for persons with advanced disease (and longer treatment courses) and therefore may not reflect the experience of persons with less advanced disease or those who are uninfected (74). Side effects associated with many of the NRTIs (e.g., ZDV or ddI) are chiefly gastrointestinal (e.g., nausea or diarrhea), and in general the incidence of adverse effects has not been greater when these agents are used in combination (72).
All of the approved PIs may have potentially serious drug interactions when used with certain other drugs, requiring careful evaluation of concomitant medications being used by an HCW before prescribing a PI and close monitoring for toxicity when an HCW is receiving one of these drugs (See Appendix). PIs may inhibit the metabolism of nonsedating antihistamines and other hepatically metabolized drugs; NEL and ritonavir may accelerate the clearance of certain drugs, including oral contraceptives (requiring alternative or additional contraceptive measures for women taking these drugs). The use of PIs also has been associated with new onset of diabetes mellitus, hyperglycemia, diabetic ketoacidosis, and exacerbation of pre-existing diabetes mellitus (75-77). Nephrolithiasis has been associated with IDV use (including in HCWs using the drug for PEP) (8); however, the incidence of this potential complication may be limited by drinking at least 48 oz (1.5 L) of fluid per 24-hour period (e.g., six 8 oz glasses of water throughout the day) (72). Rare cases of hemolytic anemia also have been associated with the use of IDV. NEL, saquinavir, and ritonavir have been associated with the development of diarrhea; however, this side effect usually responds to treatment with antimotility agents that can be prescribed for use, if necessary, at the time any one of these drugs is prescribed for PEP. The manufacturer's package insert should always be consulted for questions about potential drug interactions.
Among HCWs receiving ZDV PEP, usually at doses of 1,000-1,200 mg per day (i.e., higher than the currently recommended dose), 50%-75% reported one or more subjective complaints and approximately 30% discontinued the drug because of symptoms (7,78,79). Common symptoms included nausea, vomiting, malaise or fatigue, headache, or insomnia. Mild decreases in hemoglobin and absolute neutrophil count also were observed. All side effects were reversed when PEP was discontinued.
Preliminary information about HCWs receiving combination drugs for PEP (usually ZDV plus 3TC with or without a PI) suggests that approximately 50%-90% of HCWs report subjective side effects that caused 24%-36% to discontinue PEP (8-10). One study documented that combination regimens that included ZDV at a lower dose (600 mg per day) were better tolerated than high-dose ZDV used alone (1,000-1,200 mg per day) (10). However, serious side effects, including nephrolithiasis, hepatitis, and pancytopenia, have been reported with the use of combination drugs for PEP (9,80; J.L. Gerberding, San Francisco General Hospital, personal communication, May 1997).
Resistance to Antiretroviral Agents
Known or suspected resistance of the source virus to antiretroviral agents, particularly to one or more agents that might be included in a PEP regimen, is a concern for those making decisions about PEP. Resistance of HIV has been reported with all available antiretroviral agents (65). However, the relevance of exposure to a resistant virus is not understood. Although transmission of resistant strains has been reported (81-85), in the perinatal clinical trial that studied vertical HIV transmission (ACTG protocol 076), ZDV prevented perinatal transmission despite genotypic resistance of HIV to ZDV in the mother (66). In addition, patients generally take more than one antiretro-viral drug and, unless testing is performed, often it is difficult to know to which drug(s) resistance exists. The complexity of this issue is further compounded by the frequency of cross-resistance within drug classes.
Resistance should be suspected in source patients when there is clinical progression of disease or a persistently increasing viral load and/or a decline in CD4 T-cell count despite therapy, or a lack of virologic response to a change in therapy. Nevertheless, in this situation it is unknown whether a modification in the PEP regimen is necessary or will influence the outcome of an occupational exposure.
Antiretroviral Drugs in Pregnancy
Considerations for the use of antiretroviral drugs in pregnancy include their potential effect on the pregnant woman and on her fetus or neonate. The pharmacokinetics of antiretroviral drugs has not been completely studied in pregnant women. Some of the antiretroviral drugs are known to cross the placenta, but data for humans are not yet available for others (particularly the PIs). In addition, data are limited on the potential effects of antiretroviral drugs on the developing fetus or neonate (86). Decisions on the use of specific drugs in pregnancy also are influenced by whether a drug has specific adverse effects or might further exacerbate conditions associated with pregnancy, (e.g., drugs that cause nausea may be less tolerated when superimposed on the nausea normally associated with pregnancy).
There are data on both ZDV and 3TC from clinical trials in HIV-infected pregnant women. The most extensive experience has been with the use of ZDV after 14 weeks of gestation in pregnant HIV-infected women in phase I studies and the perinatal ACTG protocol 076 (4,87). The dose of ZDV for pregnant women is the same as that in nonpregnant persons, and ZDV appears safe and well tolerated in both women and their infants who have had a follow-up period of several years (88-90). Data from the Antiretroviral Pregnancy Registry have not documented an increased risk for birth defects in infants with in utero exposure to ZDV (91). There are limited data on use of 3TC alone or in combination with ZDV in late gestation in pregnant HIV-infected women. As with ZDV, the pharmacokinetics and dose of 3TC appear to be similar to those for nonpregnant persons. The drug appears safe during pregnancy for women and infants, although long-term safety is not known (92,93).
Carcinogenicity and/or mutagenicity is evident in several in vitro screening tests for ZDV and all other FDA-licensed nucleoside antiretroviral drugs. In some in vivo rodent studies, high-dose lifetime continuous ZDV exposure (94) or very high dose in utero ZDV exposure has been associated with the development of tumors in adult females or their offspring (95,96). The relevance of these animal data to humans is unknown. However, in 1997 an independent panel reviewed these data and concluded that the known benefits of ZDV in preventing perinatal transmission, where the risk for transmission without ZDV is 25%-30%, outweigh the hypothetical concerns about transplacental carcinogenesis (97).
No data are available regarding pharmacokinetics, safety, or tolerability of any of the PIs in pregnant women. The use of PIs in HIV-infected persons has been associated with hyperglycemia; it is unknown whether the use of these agents during pregnancy will exacerbate the risk for pregnancy-associated hyperglycemia. Therefore, close monitoring of glucose levels and careful instruction regarding symptoms related to hyperglycemia are recommended for pregnant HCWs receiving a PI for PEP. IDV is associated with infrequent side effects in adults (i.e., hyperbilirubinemia and renal stones) that could be problematic for the newborn. As the half-life of IDV in adults is short, these concerns may be relevant only if the drug is administered shortly before delivery.
RECOMMENDATIONS FOR THE MANAGEMENT OF POTENTIALLY EXPOSED HCWs
Health-care organizations should make available to their workers a system that includes written protocols for prompt reporting, evaluation, counseling, treatment, and follow-up of occupational exposures that may place HCWs at risk for acquiring any bloodborne infection, including HIV. Employers also are required to establish exposure-control plans, including postexposure follow-up for their employees, and to comply with incident reporting requirements mandated by the Occupational Safety and Health Administration (15). Access to clinicians who can provide postexposure care should be available during all working hours, including nights and weekends. Antiretroviral agents for PEP should be available for timely administration (i.e., either by providing access to PEP drugs on site or creating links with other facilities or providers to make them available offsite). Persons responsible for providing postexposure counseling should be familiar with evaluation and treatment protocols and the facility's procedures for obtaining drugs for PEP.
HCWs should be educated to report occupational exposures immediately after they occur, particularly because PEP is most likely to be effective if implemented as soon after the exposure as possible (41,55,56). HCWs who are at risk for occupational exposure to HIV should be taught the principles of postexposure management, including options for PEP, as part of job orientation and ongoing job training.
Exposure Report
If an occupational exposure occurs, the circumstances and postexposure management should be recorded in the HCW's confidential medical record (usually on a form the facility designates for this purpose). Relevant information includes
date and time of exposure;
details of the procedure being performed, including where and how the exposure occurred, and if the exposure was related to a sharp device, the type of device and how and when in the course of handling the device the exposure occurred;
details of the exposure, including the type and amount of fluid or material and the severity of the exposure (e.g., for a percutaneous exposure, depth of injury and whether fluid was injected; or for a skin or mucous-membrane exposure, the estimated volume of material and duration of contact and the condition of the skin {e.g., chapped, abraded, or intact});
details about the exposure source (i.e., whether the source material contained HIV or other bloodborne pathogen{s}), and if the source is an HIV-infected person, the stage of disease, history of antiretroviral therapy, and viral load, if known; and
details about counseling, postexposure management, and follow-up.
Exposure Management
Treatment of an Exposure Site
Wounds and skin sites that have been in contact with blood or body fluids should be washed with soap and water; mucous membranes should be flushed with water. There is no evidence that the use of antiseptics for wound care or expressing fluid by squeezing the wound further reduces the risk for HIV transmission. However, the use of antiseptics is not contraindicated. The application of caustic agents (e.g., bleach) or the injection of antiseptics or disinfectants into the wound is not recommended.
Assessment of Infection Risk
After an occupational exposure, the source-person and the exposed HCW should be evaluated to determine the need for HIV PEP. Follow-up for hepatitis B virus and hepatitis C virus infections also should be conducted in accordance with previously published CDC recommendations (98,99).
Evaluation of exposure. The exposure should be evaluated for potential to transmit HIV based on the type of body substance involved and the route and severity of the exposure. Exposures to blood, fluid containing visible blood, or other potentially infectious fluid (including semen; vaginal secretions; and cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids) or tissue through a percutaneous injury (i.e., needlestick or other penetrating sharps-related event) or through contact with a mucous membrane are situations that pose a risk for bloodborne transmission and require further evaluation (
Figure_1 and Figure_1C). In addition, 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.For skin exposures, follow-up is indicated if it involves direct contact with a body fluid listed above and there is evidence of compromised skin integrity (e.g., dermatitis, abrasion, or open wound). However, if the contact is prolonged or involves a large area of intact skin, postexposure follow-up may be considered on a case-by-case basis or if requested by the HCW.
For human bites, the clinical evaluation must consider possible exposure of both the bite recipient and the person who inflicted the bite. HIV transmission only rarely has been reported by this route (100,101; CDC, unpublished data, 1998). If a bite results in blood exposure to either person involved, postexposure follow-up, including consideration of PEP, should be provided.
Evaluation and testing of an exposure source. The person whose blood or body fluids are the source of an occupational exposure should be evaluated for HIV infection. Information available in the medical record at the time of exposure (e.g., laboratory test results, admitting diagnosis, or past medical history) or from the source person may suggest or rule out possible HIV infection. Examples of information to consider when evaluating an exposure source for possible HIV infection include laboratory information (e.g., prior HIV testing results or results of immunologic testing {e.g., CD4+ count}), clinical symptoms (e.g., acute syndrome suggestive of primary HIV infection or undiagnosed immunodeficiency disease), and history of possible HIV exposures (e.g., injecting-drug use, sexual contact with a known HIV-positive partner, unprotected sexual contact with multiple partners {heterosexual and/or homosexual}, or receipt of blood or blood products before 1985).
If the source is known to have HIV infection, available information about this person's stage of infection (i.e., asymptomatic or AIDS), CD4+ T-cell count, results of viral load testing, and current and previous antiretroviral therapy, should be gathered for consideration in choosing an appropriate PEP regimen. If this information is not immediately available, initiation of PEP, if indicated, should not be delayed; changes in the PEP regimen can be made after PEP has been started, as appropriate.
If the HIV serostatus of the source person is unknown, the source person should be informed of the incident and, if consent is obtained, tested for serologic evidence of HIV infection. If consent cannot be obtained (e.g., patient is unconscious), procedures should be followed for testing source persons according to applicable state and local laws. Confidentiality of the source person should be maintained at all times.
HIV-antibody testing of an exposure source should be performed as soon as possible. Hospitals, clinics, and other sites that manage exposed HCWs should consult their laboratories regarding the most appropriate test to use to expedite these results. An FDA-approved rapid HIV-antibody test kit should be considered for use in this situation, particularly if testing by enzyme immunoassay (EIA) cannot be completed within 24-48 hours. Repeatedly reactive results by EIA or rapid HIV-antibody tests are considered highly suggestive of infection, whereas a negative result is an excellent indicator of the absence of HIV antibody. Confirmation of a reactive result by Western blot or immunofluorescent antibody is not necessary for making initial decisions about postexposure management but should be done to complete the testing process.
If the source is HIV seronegative and has no clinical evidence of acquired immunodeficiency syndrome (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 is HIV negative at the time of exposure, but recently (i.e., within the last 3-6 months) engaged in behaviors that pose a risk for HIV transmission, is useful in postexposure management of HCWs; HCWs who become infected generally seroconvert before repeat testing of a source would normally be performed.
If the exposure source is unknown, information about where and under what circumstances the exposure occurred should be assessed epidemiologically for risk for transmission of HIV. Certain situations, as well as the type of exposure, may suggest an increased or decreased risk; an important consideration is the prevalence of HIV in the population group (i.e., institution or community) from which the contaminated source material is derived. For example, an exposure that occurs in a geographic area where injecting-drug use is prevalent or on an AIDS unit in a health-care facility would be considered epidemiologically to have a higher risk for transmission than one that occurs in a nursing home for the elderly where no known HIV-infected residents are present. In addition, exposure to a blood-filled hollow needle or visibly bloody device suggests a higher-risk exposure than exposure to a needle that was most likely used for giving an injection. Decisions regarding appropriate management should be individualized based on the risk assessment.
HIV testing of needles or other sharp instruments associated with an exposure, regardless of whether the source is known or unknown, is not recommended. The reliability and interpretation of findings in such circumstances are unknown.
Clinical Evaluation and Baseline Testing of Exposed HCWs
Exposed HCWs should be evaluated for susceptibility to bloodborne pathogen infections. Baseline testing (i.e., testing to establish serostatus at the time of exposure) for HIV antibody should be performed. If the source person is seronegative for HIV, baseline testing or further follow-up of the HCW normally is not necessary. If the source person has recently engaged in behaviors that are associated with a risk for HIV transmission, baseline and follow-up HIV-antibody testing (e.g., 3 and/or 6 months postexposure) of the HCW should be considered. Serologic testing should be made available to all HCWs who are concerned that they may have been exposed to HIV.
For purposes of considering HIV PEP, the evaluation also should include information about medications the HCW may be taking and any current or underlying medical conditions or circumstances (i.e., pregnancy, breast feeding, or renal or hepatic disease) that may influence drug selection. Pregnancy testing should be offered to all nonpregnant women of childbearing age whose pregnancy status is unknown.
HIV PEP
The following recommendations apply to situations where an HCW has had an exposure to a source person with HIV or where information suggests that there is a likelihood that the source person is HIV-infected. These recommendations are based on the risk for HIV infection after different types of exposure and limited data regarding efficacy and toxicity of PEP. Because most occupational HIV exposures do not result in the transmission of HIV, potential toxicity must be carefully considered when prescribing PEP. When possible, these recommendations should be implemented in consultation with persons having expertise in antiretroviral therapy and HIV transmission.
Explaining PEP to HCWs
Recommendations for chemoprophylaxis should be explained to HCWs who have sustained occupational HIV exposures (Figure_1 and Figure_1C). For exposures for which PEP is considered appropriate, HCWs should be informed that a) knowledge about the efficacy and toxicity of drugs used for PEP are limited; b) only ZDV has been shown to prevent HIV transmission in humans; c) there are no data to address whether adding other antiretroviral drugs provides any additional benefit for PEP, but experts recommend combination drug regimens because of increased potency and concerns about drug-resistant virus; d) data regarding toxicity of antiretroviral drugs in persons without HIV infection or in pregnant women are limited for ZDV and not known regarding other antiretroviral drugs; and e) any or all drugs for PEP may be declined by the HCW. HCWs who have HIV occupational exposures for which PEP is not recommended should be informed that the potential side effects and toxicity of taking PEP outweigh the negligible risk of transmission posed by the type of exposure.
Factors in Selection of a PEP Regimen
Selection of the PEP regimen should consider the comparative risk represented by the exposure and information about the exposure source, including history of and response to antiretroviral therapy based on clinical response, CD4+ T-lymphocyte counts, viral load measurements, and current disease stage. Most HIV exposures will warrant only a two-drug regimen, using two NRTIs, usually ZDV and 3TC. The addition of a third drug, usually a PI (i.e., IDV or NEL), should be considered for exposures that pose an increased risk for transmission or where resistance to the other drugs used for PEP is known or suspected.
Timing of PEP Initiation
PEP should be initiated as soon as possible. The interval within which PEP should be started for optimal efficacy is not known. Animal studies have demonstrated the importance of starting PEP within hours after an exposure (43,54,56). To assure timely access to PEP, an occupational exposure should be regarded as an urgent medical concern and PEP started as soon as possible after the exposure (i.e., within a few hours rather than days). If there is a question about which antiretroviral drugs to use, or whether to use two or three drugs, it is probably better to start ZDV and 3TC immediately than to delay PEP administration. Although animal studies suggest that PEP probably is not effective when started later than 24-36 hours postexposure (42,55,56), the interval after which there is no benefit from PEP for humans is undefined. Therefore, if appropriate for the exposure, PEP should be started even when the interval since exposure exceeds 36 hours. Initiating therapy after a longer interval (e.g., 1-2 weeks) may be considered for exposures that represent an increased risk for transmission; even if infection is not prevented, early treatment of acute HIV infection may be beneficial (69). The optimal duration of PEP is unknown. Because 4 weeks of ZDV appeared protective in HCWs (2), PEP probably should be administered for 4 weeks, if tolerated.
PEP if Serostatus of Source Person is Unknown
If the source person's HIV serostatus is unknown at the time of exposure (including when the source is HIV negative but may have had a recent HIV exposure), use of PEP should be decided on a case-by-case basis, after considering the type of exposure and the clinical and/or epidemiologic likelihood of HIV infection in the source (Figure_1 and Figure_1C). If these considerations suggest a possibility for HIV transmission and HIV testing of the source is pending, it is reasonable to initiate a two-drug PEP regimen until laboratory results have been obtained and later modify or discontinue the regimen accordingly.
PEP if Exposure Source is Unknown
If the exposure source is unknown, use of PEP should be decided on a case-by-case basis. Consideration should include the severity of the exposure and the epidemiologic likelihood that the HCW was exposed to HIV.
PEP for Pregnant HCWs
If the HCW is pregnant, the evaluation of risk and need for PEP should be approached as with any other HCW who has had an HIV exposure. However, the decision to use any antiretroviral drug during pregnancy should involve discussion between the woman and her health-care provider regarding the potential benefits and potential risks to her and her fetus.
Follow-up of HCWs Exposed to HIV
Postexposure Testing
HCWs with occupational exposure to HIV should receive follow-up counseling, postexposure testing, and medical evaluation regardless of whether they receive PEP. HIV-antibody testing should be performed for at least 6 months postexposure (e.g., at 6 weeks, 12 weeks, and 6 months). It is unclear whether an extended follow-up period (e.g., 12 months) is indicated in certain circumstances. Although rare instances of delayed HIV seroconversion have been reported (36,37, J.L. Gerberding, San Francisco General Hospital, unpublished data, May 1997), the infrequency of this occurrence does not warrant adding to HCWs' anxiety by routinely extending the duration of postexposure follow-up. Circumstances for which extending the duration of follow-up have been suggested include the use of highly potent antiretroviral regimens (i.e., more than two drugs) because of theoretical concerns that HIV seroconversion could be delayed, or simultaneous exposure to HCV. Data are insufficient for making a general recommendation in these situations. However, this should not preclude a decision to extend follow-up in an individual situation based on the clinical judgement of the HCW's health-care provider. HIV testing should be performed on any HCW who has an illness that is compatible with an acute retroviral syndrome, regardless of the interval since exposure. HIV-antibody testing using EIA should be used to monitor for sero-conversion. The routine use of direct virus assays (e.g., HIV p24 antigen EIA or polymerase chain reaction for HIV RNA) to detect infection in exposed HCWs generally is not recommended (34). Although direct virus assays may detect HIV infection a few days earlier than EIA, the infrequency of HCW seroconversion and increased costs of these tests do not warrant their routine use in this setting. Also, HIV RNA is approved for use in established HIV infection; its reliability in detecting very early infection has not been determined.
Monitoring and Management of PEP Toxicity
If PEP is used, drug-toxicity monitoring should be performed at baseline and again 2 weeks after starting PEP. Clinical judgment, based on medical conditions that may exist in the HCW and any toxicity associated with drugs included in the PEP regimen, should determine the scope of testing. Minimally these should include a complete blood count and renal and hepatic chemical function tests. Monitoring for evidence of hyperglycemia should be included for HCWs whose regimen includes any PI; if the HCW is receiving IDV, monitoring for crystalluria, hematuria, hemolytic anemia, and hepatitis also should be included. If toxicity is noted, modification of the regimen should be considered after expert consultation; further diagnostic studies may be indicated.
HCWs who fail to complete the recommended regimen often do so because of the side effects they experience (e.g., nausea and diarrhea). These symptoms often can be managed without changing the regimen by prescribing antimotility and antiemetic agents or other medications that target the specific symptoms. In other situations, modifying the dose interval (i.e., administering a lower dose of drug more frequently throughout the day, as recommended by the manufacturer), may help promote adherence to the regimen.
Counseling and Education
Although HIV infection following an occupational exposure occurs infrequently, the emotional impact of the exposure often is substantial (102,103). In addition, HCWs are given seemingly conflicting information. Although HCWs are told that there is a low risk for HIV transmission, a 4-week regimen of PEP is recommended and they are asked to commit to behavioral measures (i.e., sexual abstinence or condom use) to prevent secondary transmission, all of which influence their lives for several weeks to months (102). Therefore, access to persons who are knowledgeable about occupational HIV transmission and who can deal with the many concerns an HIV exposure may raise for the HCW is an important element of postexposure management.
HIV-exposed HCWs should be advised to use the following measures to prevent secondary transmission during the follow-up period, especially during the first 6-12 weeks after the exposure when most HIV-infected persons are expected to seroconvert: use sexual abstinence or condoms to prevent sexual transmission and to avoid pregnancy; and refrain from donating blood, plasma, organs, tissue, or semen. If the exposed HCW is breastfeeding, she should be counseled about the risk for HIV transmission through breast milk, and discontinuation of breastfeeding should be considered, especially following high-risk exposures. If the HCW chooses to receive PEP, temporary discontinuation of breastfeeding while she is taking PEP should be considered to avoid exposing the infant to these agents. NRTIs are known to pass into breast milk; it is not known whether this also is true for PIs.
There is no need to modify an HCW's patient-care responsibilities to prevent transmission to patients based solely on an HIV exposure. If HIV seroconversion is detected, the HCW should be evaluated according to published recommendations for HIV-infected HCWs (104).
Exposed HCWs should be advised to seek medical evaluation for any acute illness that occurs during the follow-up period. Such an illness, particularly if characterized by fever, rash, myalgia, fatigue, malaise, or lymphadenopathy, may be indicative of acute HIV infection but also may be due to a drug reaction or another medical condition.
Exposed HCWs who choose to take PEP should be advised of the importance of completing the prescribed regimen. Information should be provided about potential drug interactions and the drugs that should not be taken with PEP, the side effects of the drugs that have been prescribed (See Appendix), measures to minimize these effects, and the methods of clinical monitoring for toxicity during the follow-up period. They should be advised that the evaluation of certain symptoms should not be delayed (e.g., back or abdominal pain, pain on urination or blood in the urine, or symptoms of hyperglycemia {i.e., increased thirst and/or frequent urination}).
RECOMMENDATIONS FOR THE SELECTION OF DRUGS FOR PEP
The selection of a drug regimen for HIV PEP must strive to balance the risk for infection against the potential toxicity of the agent(s) used. Because PEP is potentially toxic, its use is not justified for exposures that pose a negligible risk for transmission (Figure_1 and Figure_1C). Also, there is insufficient evidence to recommend a highly active regimen for all HIV exposures. Therefore, two regimens for PEP are provided (Table_1): a "basic" two-drug regimen that should be appropriate for most HIV exposures and an "expanded" three-drug regimen that should be used for exposures that pose an increased risk for transmission (Figure_1 and Figure_1C) or where resistance to one or more antiretroviral agents is known or suspected. When possible, the regimens should be implemented in consultation with persons having expertise in antiretroviral treatment and HIV transmission.
Situations That Require Special Consideration
Resistance of the Source Virus to Antiretroviral Drugs
It is unknown whether drug resistance influences transmission risk; however, transmission of drug-resistant HIV has been reported (81,82) and is therefore a theoretical concern when choosing PEP regimens. If the source-person's virus is known or suspected to be resistant to one or more of the drugs included in the PEP regimen, the selection of drugs to which the source person's virus is unlikely to be resistant is recommended (69). If the resistance is to one class of antiretroviral drugs, the addition to the basic PEP regimen of a drug from another class might be considered (e.g., addition of a PI when a source patient has not been treated with a PI but has virus resistant to one or more NRTIs). It is strongly recommended that PEP be started regardless of the resistance status in the source virus; if resistance is known or suspected, a third or fourth drug may be added to the regimen until consultation with a clinical expert in the treatment of HIV infection or disease can be obtained.
Known or Suspected Pregnancy in the HCW
Pregnancy should not preclude the use of optimal PEP regimens, and PEP should not be denied to an HCW solely on the basis of pregnancy. However, as discussed previously, an occupationally exposed pregnant HCW must be provided with full information about what is known and not known regarding the potential benefits and risks associated with use of the antiretroviral drugs to her and her fetus for her to make an informed decision regarding the use of PEP. The choice of antiretroviral drugs to use for PEP in pregnant HCWs is complicated by the potential need to alter dosing because of physiologic changes associated with pregnancy and the potential for short- or long-term effects on the fetus and newborn. Thus, considerations that should be discussed with a pregnant HCW include the potential risk for HIV transmission based on the type of exposure; the stage of pregnancy (the first trimester being the period of maximal organogenesis and risk for teratogenesis); and what is known about the pharmacokinetics, safety, and tolerability of the drug or combination of drugs in pregnancy.
POSTEXPOSURE REGISTRIES
Health-care providers in the United States are encouraged to enroll HCWs who receive PEP in a confidential registry developed by CDC, Glaxo Wellcome Inc., and Merck & Co., Inc., to assess toxicity; telephone (888) 737-4448 ({888} PEP-4HIV), or write the HIV PEP Registry, 1410 Commonwealth Drive, Suite 215, Wilmington, NC 28405. Unusual or serious and unexpected toxicity from antiretroviral drugs should be reported to the manufacturer and/or FDA, telephone (800) 332-1088.
Health-care providers also should report instances of prenatal exposure to antiretroviral agents to the Antiretroviral Pregnancy Registry. The registry is an epidemiologic project to collect observational, nonexperimental data on antiretroviral drug exposure during pregnancy to assess potential teratogenicity. Referrals should be directed to the Antiretroviral Pregnancy Registry, 1410 Commonwealth Drive, Suite 215, Wilmington, NC 28405; telephone (800) 258-4263 or (800) 722-9292, ext. 39437; fax (800) 800-1052.
A protocol has been developed to evaluate HIV seroconversion in an HCW who received PEP. These events can be reported to CDC, telephone (404) 639-6425.
RESOURCES FOR CONSULTATION
Clinicians who seek consultation on HIV PEP for assistance in managing an occupational exposure should access local experts in HIV treatment as much as possible. In addition, the "National Clinicians' Post-Exposure Prophylaxis Hotline (PEP-Line)" has been created to assist clinicians with these issues; telephone (888) 448-4911. Other resources and registries include the HIV Postexposure Prophylaxis Registry, the Antiretroviral Pregnancy Registry, FDA, and CDC (Table_2).
ADMINISTRATIVE CONSIDERATIONS
Effective implementation of the elements of postexposure management detailed in these recommendations may require various types of expertise. The assessment of the severity of an exposure generally requires clinical training and experience (i.e., medical or nursing). However, the assessment of HIV infection risk and initiation of a basic PEP regimen necessitates knowledge or experience in clinical epidemiology, infection control, occupational health, or the clinical treatment of HIV. Decisions about HIV PEP are particularly complex if PIs are used or there is concern about drug-resistant virus. Thus, expert consultation when prescribing PEP is strongly encouraged. PEP protocols should list the names of readily available resources for consultation and could include policies that require infectious disease evaluation before prescribing an expanded antiretroviral regimen. However, these efforts should not delay initial implementation of PEP where it is appropriate.
TABLE 1. Basic and expanded postexposure prophylaxis regimens
