Risk of HIV After Sex or Other Exposure
Post-exposure prophylaxis -- or PEP for short -- has long been
used to minimize the chance of HIV infection among healthcare
workers exposed to the virus (primarily through accidental
It is also generally available in the emergency room to sexual
"Prophylaxis" is treatment used for the prevention of disease.
For example, Bactrim or Septra is used as a prophylaxis against
PCP (a type of pneumonia).
For HIV, anti-HIV drugs are used.4
A combination of HIV drugs must be given within 72 hours (three
days) of exposure and taken for 28 days. PEP is not a cure -- it
is not guaranteed to prevent infection. Moreover, its use,
especially in the community (or non-occupational setting),
As wonderful as the concept sounds, anyone familiar with HIV
drugs can quickly see potential problems -- among them
toxicities and the costs of the medications. In 2001, it was
reported that a phlebotomist in Chicago had to undergo a liver
transplant two weeks after beginning a PEP regimen, due to one
of the HIV medications used. As for cost, a month's worth of
only one HIV drug will cost no less than $300, and insurance is
not likely to cover what is still an experimental treatment
strategy. PEP is not to be taken lightly.
At the same time, opportunities for extending the benefits of
PEP out to the community are to be welcomed. In January, as
Positively Aware prepared this article for press, the U.S.
Centers for Disease Control and Prevention (CDC) updated the
guidelines for PEP following sexual exposure.
As Dr. Ronald O. Valdiserri, the Deputy Director of the CDC's
National Center for HIV, STD and TB Prevention, said during a
press conference call introducing the guidelines, "Far too many
Americans are becoming infected every year. Prevention is the
most effective strategy, but the severity of the problem
requires that we use all available interventions."
This article will examine the concept of PEP and
non-occupational post-exposure prophylaxis (nPEP), its
advantages and its limitations, and will explore how nPEP may
eventually impact the spread of new HIV infections in the
Not "The Morning After" Pill
PEP is never a one-time pill. It is not the "morning after pill"
equivalent for HIV.6
Nor is it a cure for the spread of HIV infections in the United
Prevention efforts that protect against any possible exposures
to HIV are still the mainstays to prevent HIV transmission and
infection. The CDC guidelines state, "the most effective methods
for preventing ... HIV infection are those that protect against
exposure to HIV. Preventive behaviors include sexual abstinence,
sex only with an uninfected partner, consistent and correct
condom use, abstinence from injecting-drug use, and consistent
use of sterile equipment by those unable to cease injecting-drug
However, PEP is an interesting treatment concept for helping to
minimize the chances of HIV infection when a non-HIV infected
person has accidentally been exposed to HIV-containing blood or
bodily secretions (such as semen or vaginal secretions),4
especially after having taken precautions.8
In the healthcare setting, accidental exposures can occur when
the healthcare worker comes into blood-to-blood contact with
HIV-infected fluids. This often occurs as accidental
needle-stick exposures, or even as a result of human bites, from
a known HIV-positive person or someone at very high risk of HIV.
When PEP is properly administered, the risk of HIV infection has
been clinically shown to be reduced by greater than 80%, in the
It can be argued that the risks of HIV infection in healthcare
settings can be similar to the risks of HIV infection in
non-healthcare or community settings (such as in sexual contact,
intravenous drug use (IDU), or other exposures)4
despite limited data8
Table 1: Summary of HIV Transmission Risk by Type of
Type of exposure (from a source known to be HIV
Risk of HIV transmission per exposure
Accidental needlestick injury
Mucosal membrane exposure
Receptive oral sex
From 0 to 0.04%
Insertive vaginal sex
Insertive anal sex
Receptive vaginal sex
Receptive anal sex
IDUs sharing needle
Source: Euro-NONOPEP Project Group
The risk of HIV infection from an accidental needle stick
exposure is between 0.2%-0.4% per exposure for healthcare
workers. The risks of HIV infection in the community setting
range from 0.01% to less than 3% per exposure, depending on risk
It has been known, however, for infection to occur after a
An important difference between the healthcare setting and the
community setting is the timing or access to treatment and the
ability to confirm the HIV status of a highly suspected source
prior to treatment initiation.
In the healthcare setting, healthcare workers have instant
access to antiretroviral treatments (usually within one to two
hours) and have a unique ability to confirm the source patient's
HIV status prior to initiation of PEP. In the community setting,
the confirmation of serostatus may be very difficult to obtain.
Also, access to treatment may take longer, especially if the
post-exposure patient does not have an established healthcare
provider, or a healthcare provider comfortable with prescribing
antiretroviral treatments, plus knowledge of a pharmacy able to
provide antiretrovirals at a moment's notice. Studies have
demonstrated the median time to access PEP treatment is
approximately 33 hours from time of exposure,8
even when established PEP resources for treatment are already in
There have been many studies showing the advantages of PEP.
Initial studies occurred in animals. Research performed in both
mice and primates have demonstrated the effects of PEP in
minimizing the chances for HIV infection.2,9
In these studies, we have learned that antiretrovirals provide
their protective effects by helping to block the uptake of HIV
from dendritic cells in the body, thus helping to prevent their
uptake into the lymphatic system. This effect usually occurs in
the first 24 to 48 hours of HIV infection.1,9
In animal studies, it was learned most of the protective effects
of PEP occurred if administered within the first 24 to 48 hours,
but also showed the effects diminish if given after 72 hours
from time of exposure. Also, these studies have demonstrated
that antiretroviral therapy needs to be administered for not
less than four weeks of treatment.1,2
From early on in the use of PEP, AZT (Retrovir, also called
zidovudine) used by itself has shown a greater than 80%
reduction in minimizing the chances of HIV infection in
This has been the basis for PEP in the healthcare setting.
Studies have shown the additional benefits in reducing the
chances of HIV infection with antiretrovirals during pregnancy.
Studies have clearly demonstrated HIV infection can be prevented
after birth in babies born to HIV-infected mothers (known as
vertical transmission), with treatment initiated in the first
few days of life. This further supports the notion that it is
possible to prevent HIV transmission in humans after potential
Recent data performed in the community setting has shown a
benefit in reducing the chances of HIV infection with PEP. In
California, the San Francisco PEP study looked at the effects of
antiretroviral combination therapy in minimizing the rates of
HIV seroconversion in mostly gay males having been exposed or
potentially exposed to HIV after a high risk sexual or injection
drug use exposure.
The nPEP regimen consisted of either lamivudine (3TC, Epivir)
and zidovudine (AZT, Retrovir) in the fixed dose combination
pill (Combivir), alone or in combination with the protease
inhibitor Viracept (nelfinavir mesylate). Viracept was only used
when the source partner's HIV status was known, or highly
suspected, to be positive and with a detectable, or
uncontrolled, viral load. Also, as a secondary measure,
lamivudine (3TC, Epivir) and stavudine (d4T, Zerit) or stavudine
and didanosine (ddI, Videx) were allowed as combination therapy
if participants were not tolerating Combivir well. The study
showed a 1% risk of seroconversion when treatments were
administered within 72 hours of exposure and when adhered to for
a 4-week treatment regimen.8
Controversies Surrounding PEP in the Community Setting
If we had treatments which could decrease the chances of HIV
infection in the community setting, would this be a license for
people to practice unsafe, high-risk sex? Data from the San
Francisco PEP study showed that the likelihood for gay men to
practice unsafe, high-risk sex was not increased when
participants were given nPEP. Only 12% of those having received
an initial course of nPEP returned for a second round of nPEP
These rates have also been demonstrated similarly in other
The majority of nPEP participants who practiced unsafe sex or IV
drug use reported a momentary lapse in judgment when requiring
their initial nPEP treatment. However, are the community
programs for HIV prevention and awareness different in San
Francisco than in other parts of the country? Many believe they
are, with California having unique prevention and outreach
programs already in place.5,8
Also, many critics of PEP in the community setting feel there is
simply not enough information to use nPEP as an effective tool
for HIV prevention.4,5,7
When used appropriately, it has been demonstrated that nPEP,
along with behavioral modifications of sexual or other high-risk
practices, can decrease the chances of HIV infection when
momentary lapses in judgment have occurred.8
And what about the cost of rolling out such programs? With
combination antiretroviral therapies ranging from approximately
$800-$2,400 per month of treatment, would community HIV PEP
place too much of a strain on already dwindling resources?
A theoretical analysis of 96 metropolitan cities nationwide was
conducted using the information gained from the San Francisco
PEP study. In the analysis, it was determined that the cost of
administering a course of nPEP treatments to minimize the
chances of seroconversion when sexual precautions were already
in place or when momentary lapses in judgment occurred during
high-risk behaviors, nPEP was more cost effective than a
lifetime cost of antiretroviral treatments and medical costs
incurred if seroconversion did occur.5
However, when looking at the costs of rolling out an nPEP
program in the community setting, it is also important to look
at the resources available for such a program. Unlike San
Francisco, many cities may not have resources in place to ensure
participants can receive care within 72 hours from time of
exposure. The San Francisco PEP study also demonstrated the
importance of combining different areas of medical care to
achieve maximum outcomes.
Such areas of medical care consisted of psychosocial services to
modify and instill safe sex behaviors among participants and to
reduce high-risk behaviors. Also, in-depth educational services
on antiretroviral therapy and adherence to antiretroviral
therapy were given to all participants in the PEP study.
Constant and consistent monitoring to prevent or decrease side
effects and minimize toxicities to antiretroviral therapy were
also administered. The costs of having such medical resources
available may be too much for many cities across the country.
And what of the success rate of the PEP program itself? In the
San Francisco study, approximately 700 participants were
studied, with 1% of participants seroconverting. Would those
numbers increase with an increase in study enrollment? Would
those same numbers be achieved in other geographic areas outside
of California? These and many more questions have yet to be
answered regarding the true benefits of PEP in the community
Currently, there are studies being conducted across the country
and internationally looking at the benefits of using nPEP as a
secondary HIV prevention tool. With more information about using
PEP in the community setting, we may gain more insight into the
potential benefits of PEP in reducing HIV transmission.
Making it Work
In order to make nPEP work, many resources need to be available.
As research has illustrated, access to PEP needs to be readily
available. People seeking PEP need access to medical providers
within the first 72 hours after potential high-risk exposure.
After that, it may be harmful to start PEP treatment, as
antiretroviral therapy at this stage may blunt cellular
responses the body may invoke against HIV infection.1,9
Not only do people need to seek help from medical providers, but
the healthcare workers need to have an active working expertise
in HIV. Due to the unknown risks involved with PEP, an educated
HIV provider is the best resource to navigate any potential
dangers associated with PEP therapy. This in and of itself may
present some additional barriers to PEP in some cities.
Knowing the behaviors that are associated with an increased risk
for HIV exposure is also important for the person seeking nPEP.
Not all behaviors carry the same risks for possible HIV
Also, the risks associated with potential HIV transmission from
a known HIV-positive source are only estimates based on per
exposure data. These risks may increase as the number of
exposures increase. (See
Also the risks do not account for differences in the status or
stage of HIV infection of the known source. Factors such as high
viral load, low CD4 T-cells, present opportunistic infections,
or even additional sexually transmitted diseases may
exponentially increase the risks associated with the per
exposure risk of HIV transmission shown above.10-12
Because of these factors, and the unpredictable nature of HIV
transmission, it is essential for all precautions to be taken
prior to any sexual or other high-risk acts, to eliminate the
potential for HIV transmission. Remember, HIV transmissions
have been documented to occur from a one time, single exposure.
Therefore, any act stated above or otherwise that presents the
potential risk to HIV transmission, no matter how small of a
risk, with a known or unknown HIV-positive source, is considered
a high-risk behavior.4,10
Which Meds to Take
The new CDC guidelines highlight the study data we currently
have and also make suggestions on the antiretrovirals medical
providers may wish to use for nPEP treatments.7
The antiretrovirals used in nPEP are to be given either as a two
or a three-drug combination (see
For a free copy, write to AIDSinfo, P.O. Box 6303, Rockville, MD
0849-6303 or call 1-800-HIV-0440 (1-800-448-0440). Visit
The CDC points out that each course of PEP or nPEP prescribed
should be a decision between the prescriber and the patient, and
determined on a case-by-case basis.7
This means that each regimen prescribed should be individualized
according to the needs of the patient as well as the situation
Two-drug combinations may be prescribed if the known or
suspected HIV-infected source has an undetectable viral load. A
three-drug regimen should be prescribed if the source has a
detectable or uncontrolled viral load, especially if
experiencing while on a protease-based regimen.
However, there is no medical evidence that a three-drug regimen
is any more effective than a two-drug regimen from the available
information on nPEP we have to date.7,8
The rationale for using a three-drug regimen is based on the
assumption that a triple-combo highly active antiretroviral
regimen (HAART) is more suppressive to HIV replication.
Also, the cost and complexity of the regimen prescribed should
be considered, to ensure that the individual will be able to
successfully complete the course prescribed. Again, there is
toxicity and cost for the individual to weigh. Potential
barriers to treatment should be addressed before starting PEP or
Because the antiretrovirals used as treatments in nPEP are the
same antiretrovirals used in treating HIV, the side effects and
the adherence issues are the same. Therefore, when people are
seeking nPEP, it is important to know what to expect when taking
Potential side effects common to antiretrovirals include nausea,
vomiting, diarrhea, and increases in cholesterol and blood
glucose. Liver impairments, rare allergic reactions and other
serious side effects may occur when HIV antiretrovirals are
All the Pills, All the Time
Also of importance is the way in which the antiretrovirals need
to be taken. Many antiretrovirals need to be taken in doses of
multiple pills taken multiple times a day, rarely just one pill,
once a day. This means that following and completing the course
exactly as prescribed (called "adherence") may be difficult for
some to accomplish. However, strict adherence is required to
ensure the maximal response to diminish the chance of HIV
infection from occurring.
Most prescribed antiretrovirals in an nPEP regimen would be
dosed either once every 24 hours, once every 12 hours, or a
combination of the two, depending on the medication(s)
prescribed. As with HIV treatment, it can be reasonably assumed
that treatment for prevention of possible infection should be
followed just as strictly (if not more so) with little room for
error in missing doses or even the timing of doses.
Not Just Pills
In addition to taking the antiretrovirals for nPEP treatment,
many studies have shown the true successes of nPEP treatment
come from the integration of both medical education and
Teamed together, medical education and behavioral counseling
techniques have shown to be detrimental not only for prevention
of the current exposure to HIV, but for preventing other
possible future exposures from occurring.
Most studies have shown accidental re-exposures to HIV to be
minimal; however, most studies have also included in-depth
education on both the prescribed medication regimen and
education on improving current behaviors to prevent another
accidental exposure from reoccurring.
Since antiretroviral regimens are complex, medication education
is a requirement. This helps ensure those taking antiretrovirals
are knowledgeable not only on how to incorporate taking the
medications into their daily lives, but also on managing the
side effects as they occur to help ensure adherence for the
entire course, to ensure maximal success in prevention.
As with any medical information, its important to know all the
facts and to be as prepared as you can be. HIV knowledge and
prevention is needed more now than ever before. HIV infection
rates have been on the rise worldwide with over 40,000 new HIV
infections occurring in the U.S. each year alone.
Arming ourselves with information on prevention and treatment
techniques are the only tools currently available to help
prevent the spread of infection.4,7
Post-exposure prophylaxis (either PEP or nPEP) is only to be
used when all other precautions to prevent HIV exposure in the
first place have failed.
When deciding to engage in sexual practices or other activities
which may place one at risk for HIV exposure, it is also
important to make the decision to be regularly tested for HIV.
Without regular HIV testing and knowledge on preventing
exposures to HIV, we may never prevent the spread of this virus
with currently available tools.
PREP -- Pills Before Sex
Another treatment concept in minimizing the chances of HIV
infection is PREP (pre-exposure prophylaxis). This is not to be
confused with PEP or nPEP.
PREP is the use of antiretroviral therapy prior to unintentional
or accidental exposures to HIV infection. Data from animal
studies used to support the therapeutic effects of PEP will be
put to the test in a large, placebo-controlled, multi-centered
international HIV prevention study sponsored by the CDC to test
the effects of using PREP.
Also known as Project T, this study in San Francisco will look
at using tenofovir (Viread) as a once-a-day treatment to prevent
or minimize the spread of new HIV infections. Participants as
well as researchers will both be blinded (meaning neither will
know who is receiving the actual drug or the placebo). For this
and many reasons, participants will be counseled on the
importance of practicing safe sex and using safer techniques to
minimize the chances of new HIV infections. Participants will
also be reminded that unless such practices are used, they may
not be protected from HIV infection.13
The effects of this study will not be known until the study is
completed a few years down the road. Until any results are
revealed, we will not have any answers on whether such a
treatment concept will even work. And until such results are in,
it will be important for people to understand this concept
should not be tried outside of a study.
nPEP is an interesting treatment concept in helping to reduce
the chances of HIV infection, particularly when all other
precautions have been taken. It is a concept that has been
studied in animals, has been shown to potentially work in
humans, and may one day be another tool in helping to prevent
the spread of new HIV infections.
However, to date, there is limited data to demonstrate the true
effects of PEP in the community or non-healthcare setting. PEP
is not a cure for the spread of HIV infections. It is not 100%
effective. It is not even a substitute for true prevention
measures, such as preventing the spread of HIV through
practicing behaviors that protect against exposure to HIV.
But when all other precautions have been taken, nPEP may be a
helpful tool to minimize the chances of HIV infection when an
accidental, high-risk exposure has occurred. Although promising,
without more data on PEP in the community setting, we do not
know the full impact of nPEP in helping to reduce the spread of
new HIV infections.
Tony Hosey, Pharm.D., is an HIV specialty pharmacist who serves
as the Pharmacy Manager for StatScript Pharmacy in Chicago and
on the Adjunct Faculty of the Chicago College of Pharmacy.
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