Lowering the 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 needlestick injuries).1-3 It is also generally available in the emergency room to sexual assault survivors.

"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), remains controversial.

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 community setting.

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 States.

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 use."4,7

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 healthcare setting.2

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 (see Table 1).

Table 1: Summary of HIV Transmission Risk by Type of Non-Occupational Exposure
Type of exposure (from a source known to be HIV positive)Risk of HIV transmission per exposure
Accidental needlestick injury0.2%-0.4%
Mucosal membrane exposure0.1%
Receptive oral sexFrom 0 to 0.04%
Insertive vaginal sex<0.1%
Insertive anal sex<0.1%
Receptive vaginal sex0.01%-0.15%
Receptive anal sex<3%
IDUs sharing needle0.7%
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 behaviors.1,2,4 It has been known, however, for infection to occur after a single exposure.

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 place.

Research Findings

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 healthcare workers.2 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 exposure.2

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 treatment.

These rates have also been demonstrated similarly in other studies.3,7,8 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 setting.

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 transmission.1,10-12 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 Table 1.)

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 Table 27).

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 www.aidsinfo.nih.gov.

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 which occurred.

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 nPEP treatments.

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 the medications.

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 taken.

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 behavioral counseling.8 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.

Be Informed

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. E-mail: thosey@chronimed.com.


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Additional Information6

National Resources

For physicians who are willing to provide nPEP:

AIDS Survival Project

HIV/AIDS Treatment Information Service

National AIDS Hotline

National HIV PEP Registry
1-877-HIV-1PEP (medical providers only)

Local Resources

nPEP is offered at:

Whitman-Walker Clinic, Washington, DC

Fenway Community Health Center, Boston, MA

San Francisco City Clinic, San Francisco, CA

Beth Israel Medical Center, New York City, NY

Howard Brown Health Center, Chicago, IL

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