Much of the work we do in HIV prevention is aimed at trying to stop people from engaging in behaviours that could expose them to HIV and potentially lead to infection. But what happens if someone thinks they may have already been exposed to HIV? Is there a way we can stop them from getting infected? Post-exposure prophylaxis, or PEP, could be an option.
What is post-exposure prophylaxis?
With PEP, an HIV-negative person who may have been exposed to HIV takes anti-HIV drugs prescribed by a doctor to prevent infection. These are the same drugs that people living with HIV take. PEP involves taking two or three of these drugs for a period of one month. To effectively reduce a person’s risk of becoming HIV-positive, PEP must be taken within 72 hours of possible exposure to HIV but ideally as early as possible.
In the world of PEP, exposure to HIV is often divided into two categories: occupational exposure and non-occupational exposure. “Occupational” exposure refers to exposure to HIV at work, in a healthcare setting. For example, a healthcare provider could be exposed to HIV through a needlestick injury at work. “Non-occupational” exposure refers to exposure to HIV through sex or drug use, for example, when a person shares a needle or has sex without a condom.
What is the rationale for PEP?
In the first one to three days following exposure to HIV, there is a ‘window of opportunity’ when taking PEP might prevent an HIV infection from occurring. During this ‘window of opportunity,’ the virus is busy infecting cells at the site of exposure (such as in the anus, penis or vagina). Once the virus is inside a cell, it starts replicating to produce more HIV (also known as virions). After a few days, these new HIV virions start to spread throughout the body; once this happens, infection is permanent. The theory is that if PEP is given to a person early enough, it can stop the virus from replicating at the initial site of exposure, preventing virions from spreading throughout the body – stopping the infection from becoming permanent. The cells that initially became infected would eventually die out and the virus would not be able to replicate.
What is the evidence on PEP?
There is some evidence that suggests that providing PEP after a potential exposure to HIV can help reduce a person’s risk of HIV infection. However, we also know that PEP is not 100% effective, meaning that it will not prevent all HIV infections.
Learn more about the evidence on PEP
Primate (monkey) studies
Monkeys and other primates are closely related to human beings, which is why we conduct research on them. It helps us understand how an intervention or medication may work on humans. While monkey studies are useful, we should be cautious when interpreting the results because they are not always able to accurately predict what the effect will be in humans. Primates cannot be infected by HIV; however, they can be infected by monkey viruses that are very similar to HIV.
In monkey studies, taking PEP for one month protected almost all of the monkeys against infection by HIV-like viruses., However, when monkeys were given anti-HIV drugs for only 10 days, half of them became infected and when they were given PEP for only three days, all of the monkeys became infected.
In two monkey studies, initiating PEP within 36 hours of exposure provided more benefit than if anti-HIV drugs were started 72 hours after exposure to HIV-like viruses.,
The longer the wait to start PEP after initial exposure to the virus, the less able PEP was to prevent HIV infection. Based on the ‘window of opportunity’ theory, we can anticipate that for humans, PEP would also need to be started soon after exposure.
In monkeys, higher doses of anti-HIV drugs were associated with higher levels of protection against infection. However, similar to HIV treatment in humans, figuring out the optimal dose of anti-HIV drugs must be a trade-off between maximizing the effectiveness of PEP and minimizing the side effects.
Mother-to-child transmission
The prevention of mother-to-child transmission is one of the success stories in HIV prevention. Giving anti-HIV drugs to an HIV-positive mother during pregnancy, labour and birth and to the baby after birth has proven to significantly reduce the risk of HIV transmission from the mother to the child. There are three ways anti-HIV drugs protect the baby from becoming HIV-positive:
When a pregnant woman living with HIV takes anti-HIV drugs, it is likely that her viral load will be low. This means that her unborn baby will be exposed to less HIV while in the womb.
Anti-HIV drugs are able to cross the placental barrier. This provides PEP protection to the fetus. (It also provides protection before exposure to HIV which is called pre-exposure prophylaxis, or PrEP. The topic of PrEP will be covered in an upcoming issue of Prevention in Focus.)
Anti-HIV drugs provided to the newborns of HIV-positive women also provides additional PEP protection.
The dramatic success of the prevention of mother-to-child transmission with the use of anti-HIV drugs suggests that PEP may also protect against other routes of HIV exposure.
Human studies on PEP
Two studies that compared the number of HIV infections in people who took PEP to the number of infections in those who did not provide some evidence that taking PEP reduces the likelihood of humans becoming infected with HIV after a recent exposure. However, these studies show that PEP does not eliminate the risk of HIV infection.
One study examined the usefulness of PEP by looking at 712 healthcare workers in Europe and the US who were exposed to HIV in the workplace. The study compared two groups of healthcare workers: those who got HIV from a needlestick and those who did not get HIV despite a needlestick injury. The researchers looked to see how PEP use differed in these two groups. The study found that healthcare workers who used PEP were 81% less likely to become infected than those who did not use PEP. This means that while PEP appeared to have provided protection from HIV seroconversion, this protection was not 100%. Nine of the 256 healthcare workers became HIV-positive despite taking PEP.
The second study followed a group of high-risk gay men and other men who have sex with men who were provided access to PEP if and when they needed it. Over the course of the study, 68 men took PEP after a potential high-risk exposure to HIV while 86 men did not. Of the 68 men who took PEP, one person became infected; and of the 86 men who did not take PEP, 10 became infected. This means that there were 87% fewer infections among the men who used PEP; however, the authors did not perform a test to determine if the difference was real or due to chance. Even if they had, this was an observational study (and not a randomized control study), which makes it impossible to draw any real conclusions about the ability of PEP to prevent HIV infections!
In addition to these two studies, there are a number of other studies that looked for HIV infections in PEP users. However, these studies did not have a control group (a group who don’t use PEP), which means we can’t tell if there were fewer HIV infections in people who used PEP compared to people who didn’t use PEP. Therefore, these studies cannot be used to tell us if PEP is effective or not. However, these studies are still important as they show us that HIV infections continue to occur despite PEP use and they therefore confirm that PEP is not 100% effective.
What does someone need to know to access PEP?
People at risk need to know that PEP exists. If people are unaware of PEP, they won’t know that PEP is an option in the event of a high-risk behaviour that could result in being exposed to HIV. Very little research has been done to determine how many people are aware of PEP; however, based on the research that has been done, it seems that only a small proportion of gay and heterosexual men and women, even in cities with well-established PEP programs, are aware of PEP., , ,
People at risk need to know that time is of the essence. The later someone starts PEP, the less likely it is to prevent HIV infection. The best time to start PEP is immediately after exposure. However, PEP has some ability to prevent HIV infection up to 72 hours after infection.
People at risk need to know where to go. PEP must be prescribed by a doctor. Since time is of the essence, people need to be able to access services that are always open, such as emergency rooms. As a service provider, it may be important for you to know if there is a physician or healthcare facility in your area willing to prescribe PEP. If there isn’t, perhaps your organization can inform local clinicians of PEP and push for access to PEP for your clients.
Anyone accessing PEP will be tested for HIV. PEP is used to prevent HIV, not to treat it. People who go to a healthcare facility for PEP will be tested for HIV. They will still be prescribed PEP while the test results are pending; however, if the result is positive, PEP may either be discontinued or the anti-HIV drugs may be changed to HAART (highly active antiretroviral therapy) to treat the person’s HIV infection.
PEP can be costly and it may have to be paid for out of pocket. The cost of a full course of PEP is approximately $1100 to $1500. PEP may be covered by some private insurance plans and some public health insurance plans, depending on the province and the nature of the exposure. However, many at-risk individuals may not have access to any drug coverage and may not be able to afford it. There may be a need for advocacy in your area or province to fight for universal access to PEP.
People on PEP may experience side effects. Depending on the anti-HIV drugs prescribed, people may experience side effects from PEP, such as fatigue, nausea or diarrhea. This can cause people to stop taking their PEP drugs as prescribed, which can decrease the ability of the medications to prevent HIV infection and increase the likelihood of being infected with a drug-resistant strain of HIV.
People on PEP have to be monitored by a doctor. Testing for toxicity will be required to make sure the drugs are not causing harm to the body. The type of tests may differ depending on the anti-HIV drugs that are prescribed but would likely include liver and kidney tests.
PEP can fail to prevent HIV infection if someone doesn’t take the anti-HIV drugs as prescribed. Taking the anti-HIV drugs exactly as prescribed (also known as adherence) is central to the success of PEP. If someone doesn’t take their PEP as prescribed, then HIV infection could occur. There are two issues with adherence:
Some people might start PEP but stop using it early (before the four weeks are over). In research studies 24% to 78% of people who started PEP stopped taking it early.
Some people may not take their PEP exactly as prescribed. For example, some people may occasionally forget doses, or take only every second dose.
Drug resistance can develop if a person doesn’t take the anti-HIV drugs as prescribed. If a person becomes HIV-positive due to non-adherence, they may develop drug resistance. When someone does not take PEP as prescribed, the amount of anti-HIV drugs in the blood can be too low to suppress the HIV, which can allow the virus to evolve and develop resistance. It is important to understand that infection with a drug-resistant strain of HIV limits a person’s future treatment options. If a person with a drug-resistant strain of HIV subsequently infects someone else with HIV, drug resistance spreads within the community.
Community agencies can provide adherence support for people on PEP by providing ongoing consultation and encouragement to help people take PEP exactly as prescribed and to complete their treatment.
PEP may fail to prevent HIV infection due to drug resistance. If a person is exposed to a drug-resistant strain of HIV and the person is prescribed the drug they are resistant to, as part of their PEP regime, then PEP may fail to prevent HIV infection. Unfortunately, there is no way to know within the first one to three days if someone has been exposed to drug-resistant HIV.
Using PEP inappropriately
Some policy makers are concerned that promoting PEP may have a negative effect on people’s behaviour. They worry that PEP may lead to more people participating in risky sex or injection practices, and that we could end up with more HIV infections than before. The other issue is that PEP does not protect against hepatitis B or C, or other sexually transmitted infections. Any increase in risky behaviours could lead to an increase in these as well.
This stems from a fear that people may look at PEP like the ‘morning after pill’ – a quick fix to any behaviour that could result in their getting HIV. However, PEP is far from a quick fix. As we already know, PEP is not 100% effective and it can be difficult to tolerate due to its potential side effects.
The research done to date has found no increase in risk behaviours among those who have accessed PEP., Furthermore, there is little evidence that people continue to use PEP after their first use. This may be because all of the PEP programs that were researched had strong risk-reduction counselling services. This could explain why risky behaviours didn’t increase among PEP users. It also highlights the need for risk reduction counselling for all people who access PEP.
What are the guidelines for PEP in Canada?
The Joint United Nations Programme on HIV/AIDS (UNAIDS) has guidelines for universal access to PEP, as do many countries in the developed world, including the US, UK, France and Australia. Surprisingly, there are no national guidelines for PEP use in Canada. The Canadian STI guidelines mention PEP for occupational exposure; however, these make no mention of PEP use for non-occupational exposure. It is important for us to push for the development of national guidelines that stress universal access to PEP similar to those of the US and many other countries.
Some provinces in Canada have their own guidelines, some for occupational exposure, some for both occupational and non-occupational exposure (and some for specific types of non-occupational exposure, such as sexual assault). Even if your province has guidelines, they may not be followed in your area, because the decision about offering PEP often lies with local healthcare providers, such as hospital emergency rooms. To find out about access to PEP in your area, try contacting your local hospital, infectious disease doctor and/or family physician that provides HIV care in your area. Ask them whether they provide PEP for non-occupational exposure to HIV and what they would suggest you tell your clients about accessing PEP.
Cost-effectiveness
Cost-effectiveness is a way of determining if the benefits gained by an intervention are worth the costs required to provide it. This kind of analysis is often used to guide public health decision making. In the field of HIV prevention, an intervention is generally considered to be cost-effective if the cost of preventing one infection is lower than the cost of treating a person who is infected with HIV. Studies show that it isn’t cost-effective to give PEP to everyone. Before offering PEP, it is important to screen people to determine if there is a real risk. Studies have found that it is cost-effective to promote PEP, as a public health measure, under the following circumstances:
If a person’s partner is known to be HIV-positive, then it is cost-effective to use PEP for any activity that could potentially transmit HIV.
If the HIV status of the partner is unknown, PEP is cost-effective for gay men practicing receptive anal sex. It may also be cost-effective for people who share needles and for women who may have been exposed to HIV through unprotected anal or vaginal intercourse., , , , The use of PEP for other kinds of exposures is not considered cost-effective because of the low risk of transmission and the very high cost of PEP.
People who are accessing PEP for an exposure to a person whose HIV status is unknown should be encouraged, if possible, to bring the partner to the clinic to be tested for HIV even if PEP has already been started. If the partner tests negative, then there is no risk of HIV transmission and PEP can be avoided or stopped. This will save money and avoid any unpleasant side effects that may result from taking PEP.
An example of a PEP program in Canada
Clinique médicale l'Actuel, based in Montreal, is one of the only clinics in Canada that has established a program that offers PEP to people who may have come into contact with HIV through risky sex or drug use. While other clinics may offer PEP on a case-by-case basis, Clinique médicale l'Actuel engages in an ongoing poster campaign in the gay community in Montreal to increase awareness of PEP and encourage people at risk to use it. While the services offered by the clinic are available to everyone, their promotion of their PEP service specifically targets gay and bisexual men, because of their increased risk of HIV.
The service offers access to PEP and helps individuals adhere to PEP for the 28 days. In addition to PEP, the clinic offers other services, such as testing and counselling for sexually transmitted infections, HIV, hepatitis B and hepatitis C. It also provides safer sex education. Since people who access PEP have recently had a risky encounter, they may benefit from these additional services.
Clinique médicale l'Actuel provides universal access to PEP. While the program specifically targets gay men, they have prescribed PEP to others at risk of infection. In Quebec, the cost of PEP is covered, either through private insurance (if the person has insurance) or by Quebec’s provincial drug plan.
Next steps
There is some research that shows us that PEP can prevent HIV infections if people take it soon enough after exposure and as prescribed. Despite this evidence, only a very small proportion of people at high risk for HIV are aware of PEP. Furthermore, the availability of PEP varies across the country and there are no national guidelines on PEP use and no strategy to ensure access for those in need.
Access to PEP in Canada currently depends on whether there is a healthcare provider in your area willing to prescribe PEP to people who may have been exposed to HIV through sex or drug use. If PEP is available, your agency may have a role to play to ensure that messaging about PEP is clear, to help people make informed decisions about PEP use, and to support those who are taking PEP. If PEP is not available in your area, then advocacy may be the key to making it available and to ensuring universal access.
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