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Post-exposure Prophylaxis: PEP
What to do if you have potentially been exposed to HIV
Post-exposure prophylaxis (PEP) can be prescribed for people who have potentially been exposed to HIV. This form of HIV treatment can prevent the virus from becoming established in the body of someone who has been exposed.
PEP treatment can be accessed from clinics and health centres in many parts of the world.
PEP is particularly important for people who have been sexually assaulted or people who have been exposed to blood through a needle injury or other accident at work. 1
How does post-exposure prophylaxis (PEP) work?
Post-exposure prophylaxis is antiretroviral drug treatment that is started immediately after someone is exposed to HIV. The aim is to allow a person’s immune system a chance to provide protection against the virus and to prevent HIV from becoming established in someone’s body. It usually consists of a month long course of two or three different types of the antiretroviral drugs that are also prescribed as treatment for people living with HIV. 2
The World Health Organisation recommends prescribing zidovudine and lamivudine as the preferred regimen, stating that countries are generally advised to use the same regimens as they would for treating HIV. The British HIV Association recommend a combination of drugs called Truvada (tenofovir and emtricitabine) and Kaletra (lopinavir and ritonavir).
Effectiveness of PEP
Post-exposure prophylaxis has been studied in animal trials and human trials (see below). The cumulative evidence is enough to suggest that PEP might be effective in reducing the risk of HIV infection. This conclusion is widely recognised and as a result, a number of countries have produced guidelines suggesting the possible use of post-exposure prophylaxis in both occupational circumstances (for example a health-care worker who has been exposed in a hospital) and non-occupational circumstances (for example a person who has had unprotected sex). They tend to suggest that, as it is not 100 percent effective, post-exposure prophylaxis should only be used as a very last resort. 3
In cases where PEP is used, there are various factors that can affect its effectiveness. 4
- Delayed initiation
In order for post-exposure prophylaxis to have a chance of working, the medication needs to be taken as soon as possible, and within 72 hours of exposure to HIV. Left any longer and it is thought that the effectiveness of the treatment is severely diminished.
- Resistant virus
The person who potentially transmitted HIV (the ‘source’) may have a drug-resistant HIV, which could make PEP ineffective.
It is very important that a person using PEP takes the treatment correctly as prescribed by their doctor or healthcare worker and adheres to the full 28-day course. Shortfalls in the provision of counselling and prescription of medicines as well as their side effects, have all been cited as reasons for refusal and non-completion of PEP. 5
Who can benefit from PEP?
- People exposed to blood or bodily fluids at work
Globally, it is a common occurrence for people to be exposed to blood or bodily fluids in occupational circumstances, particularly for health care workers. Since the beginning of the 1990s in most areas of North America and Europe, post-exposure prophylaxis has been available to health workers as an important aspect of safety in the workplace. 6 The World Health Organisation recommends that PEP be made available as much as possible for this group. 7
- Victims of rape or sexual assault
PEP is especially important for children who have been sexually assaulted, as they could be particularly vulnerable to skin tearing that comes with aggravated sexual intercourse. 8 It has been found that there are often low rates of adherence to PEP among victims of sexual assault, potentially due to stigma, trauma following rape and assault, treatment side effects and a lack of support. 9 WHO recommends that PEP be made available as much as possible for this group.
- People who may have been exposed to HIV through consensual sexual contact
PEP may be recommended if it is known that the sexual partner has HIV. Otherwise, it is often not recommended, as risks may outweigh the benefits. 10 This can vary depending on the setting, or whether the sexual partner is from a ‘high-risk group’. PEP would rarely be recommended in cases of non-penetrative sex.
- People potentially exposed through needles
For people who have shared needle equipment, if it is known that the other person who used the needle has HIV then PEP may be recommended. For people who have had a needle stick injury from a discarded needle outside of a healthcare setting, PEP is not usually recommended, because the virus cannot survive long outside of the human body so it is very unlikely that the needle could infect somebody. 11
Risks and side effects
As with most antiretroviral drugs, post-exposure prophylaxis can cause side effects such as diarrhoea, headaches, nausea / vomiting and fatigue. Some of these side effects can be quite severe and it is estimated that 1 in 5 people give up the treatment before completion.
There is also the risk that taking PEP may cause a person to develop drug resistance should the patient become infected with HIV and need to be treated with antiretroviral drugs. 12
Various medical bodies have released guidelines on how PEP is accessed and by whom. There is a general consensus that the provision of PEP needs to be judged on a case-by-case basis, and the decision about whether to administer PEP should be made on a confidential and non-discriminatory basis, with informed consent. 13 In America anybody who believes they have been exposed to HIV is able to ask for post-exposure prophylaxis treatment at accident and emergency areas in hospital, through GUM or HIV clinics, and via some medical doctors experienced in treating HIV in several countries.
Guidelines released in 2011 by the 'British Association for Sexual Health and HIV PEPSE Guidelines Writing Group' outlined the circumstances that may warrant the use of PEP. 14 The recommendations, specific to the UK, consider the risk of HIV infection associated with certain factors; for example how the individual was potentially exposed, the HIV status of the ‘source’ individual and whether they are from a high or low prevalence area. The WHO also recommends that if possible the HIV status of the ‘source’ individual should be ascertained. 15
In the context of occupational settings, it is particularly important that PEP is available to protect and retain professional staff, particularly in places where there are health-worker shortages. 16
Some believe that the increasing availability of PEP will lead to behavioural changes. The theory is that if PEP is readily available people will be less likely to use condoms or will be less cautious, knowing that there is a potential back up. 17
“Rape survivors are not receiving vital anti-HIV treatment due to ignorance and a lack of basic treatment procedure at government health facilities and justice departments.”
It has also been suggested that if PEP is available more widely, people may use PEP repeatedly. However, various studies have shown that increasing awareness and availability of PEP does not lead to increasing risky behaviour. There is also little evidence showing that people would frequently rely on PEP, probably due to the adverse side effects that the treatment can involve. In particular a study in the US showed that “people reduced their risk behaviour after using PEP, rather than increasing it”. 18
Unfortunately there are still some places around the world where PEP is being denied to people who need it. For example research in South Africa revealed that many victims of rape were not receiving PEP treatment.
“Rape survivors are not receiving vital anti-HIV treatment due to ignorance and a lack of basic treatment procedure at government health facilities and justice departments”(IRIN, 2007) 19.
Homophobia and lack of understanding regarding male-on-male rape also explain why some men in South Africa do not access PEP treatment. 20
Cost-effectiveness of PEP
The question of who should receive PEP has proved to be quite controversial. Several cost-benefit analyses have revealed that providing PEP to all non-occupational exposures is not an economically efficient use of limited HIV treatment resources. 21 Making PEP available appears to be cost-effective only when the patient has engaged in unprotected receptive anal intercourse or when the patient knows the HIV status of the partner.
However, the demand for PEP does not always reflect cost-effectiveness. A ten-year review of non-occupational PEP requests recorded at a Swiss clinic found an 850 percent increase in the number of people requesting PEP in the ten-year period and 58 percent of requests were for heterosexual exposure. 22 Due to its potential benefit, there is also a strong human rights based case for prescribing PEP.
The science, trials and development of PEP
Animal studies of post-exposure prophylaxis
Various animal studies have been carried out to test the effectiveness of post-exposure prophylaxis. Macaques, a type of monkey, tend to be used in animal HIV drug trials. As macaques cannot be infected with HIV, the drugs are tested against either HIV type-2, simian immunodeficiency virus (SIV) or a combination of HIV and SIV known as simian/human immunodeficiency virus (SHIV).
One monkey study investigated whether 16 pig-tailed macaques would be protected from infection when given the antiretroviral drug tenofovir after intravaginal exposure to HIV type 2. 23 None of the 4 macaques that started the treatment 12 hours after exposure became infected. The outcome was the same with the 4 macaques that received post-exposure prophylaxis 36 hours after exposure. In the 72-hour group, one of the macaques became infected after 16 weeks. The study concluded that early intervention with an antiretroviral form of PEP such as tenofovir might be successful in preventing infection after vaginal exposure.
The timing of administering post-exposure prophylaxis and the duration of the course of treatment has been a highly significant factor in all of the animal studies. HIV takes around 3 days to reach the lymph nodes (components of the immune system), and it takes a further 2 days to reach the blood cells. There is therefore a small temporary “window” during which the infection can be blocked. This can be seen in another study of tenofovir post-exposure prophylaxis tested on 24 macaques. 24 The results showed that a 4-week regimen of tenofovir started within 24 hours of exposure completely protected the macaques from SIV. Starting the treatment between 48 and 72 hours of infection was largely ineffective. Treatment started within 24 hours of exposure but only administered for 3 days proved to be just as ineffective.
Human trials of PEP
A number of small-scale studies have investigated the efficacy of post-exposure prophylaxis in humans by looking at occupational exposures to HIV. Health care workers tend to be at a slightly higher risk of being infected with HIV due to the nature of their work (although this risk is still very low). The most frequent exposures to HIV-infected blood in the occupational setting are caused by needle stick injuries or cuts with sharp objects. Zidovudine is the drug that is primarily prescribed after an occupational exposure to HIV and it is the only drug that has been tested in trials on health care workers. Nowadays most treatment starter packs contain a combination of zidovudine, lamivudine and nelfinavir, as it is generally thought that combination drug therapy is more effective than zidovudine alone.
The results of one occupational exposure study showed that taking a course of zidovudine after exposure reduced the risk of HIV infection by approximately 81 percent. 25 These results cannot be taken as absolute, especially when there have been at least 13 reported cases where PEP has failed in health care workers worldwide. 26 For some of these cases there was no plausible explanation for why PEP might have failed and therefore PEP cannot be considered as 100 percent effective.
One study enrolled 891 people who had requested post-exposure prophylaxis after possible non-occupational HIV exposure (e.g. sexual exposure or injecting drug use). 27 The participants were all provided with a 28-day course of various combinations of zidovudine, lamivudine, stavudine and didanosine. Six out of the 700 that returned for testing after 12 weeks were HIV positive. However all 6 had had possible HIV exposures up to 6 months before commencing PEP. Therefore it was very difficult to determine the exact moment of exposure and whether PEP had been successful or not. There is a distinct lack of definitive evidence to show that PEP can be effective in non-occupational settings. Studies have generally concluded that PEP ‘might’ reduce the risk of HIV infection, but none have been able to say that it is a definite preventative.
Other observational evidence has been gathered from studies of survivors of sexual assault. In a South African study of 480 rape survivors taking a 6-week course of zidovudine and lamivudine, only one woman became HIV-positive. 28 Another study looked at 2,000 non-occupational exposures to HIV from four countries (Australia, France, Switzerland, and the United States). Out of 350 people treated with PEP who reported being exposed to HIV-infected sources, none became infected as a result of PEP failure.
Is there a future for PEP?
Post-exposure prophylaxis is not going to be enough to significantly reduce the worldwide spread of HIV. It is a short-term preventative measure that is used as an ‘emergency’ precaution. PEP is considered as the very last resort in HIV prevention and should only be used when all other methods of HIV prevention have failed. However, with increasing widespread availability and further awareness, PEP can offer more people a way to reduce the risk of HIV infection, especially in cases of sexual assault or where the status of the partner is known.
- 1. WHO & ILO (2007) ‘ Post-exposure Prophylaxis to Prevent HIV Infection’
- 2. BHIVA (2011) ‘ UK guideline for the use of post-exposure prophylaxis for HIV following sexual exposure’
- 3. BHIVA (2011) ‘ UK guideline for the use of post-exposure prophylaxis for HIV following sexual exposure’
- 4. BHIVA (2011) ‘ UK guideline for the use of post-exposure prophylaxis for HIV following sexual exposure’
- 5. Oldenburg, C.E. et al (2014) ' Adherence to post-exposure prophylaxis for non-forcible sexual exposure to HIV: a systematic review and meta-analysis' AIDS Behaviour 18(2):217-225
- 6. Centers for Disease Control and Prevention (2009) ‘Post-Exposure Prophylaxis’
- 7. WHO / ILO (2007) ‘ Post-exposure Prophylaxis to Prevent HIV Infection’
- 8. CHIVA (2011) ‘ Post-Exposure Prophylaxis (PEP) Guidelines for children and adolescents exposed to blood-borne viruses’
- 9. Carter M. (2012, 16th March) ‘ Poor adherence to HIV PEP after sexual assault’ National AIDS Manual (NAM)
- 10. BHIVA (2011) ‘ UK guideline for the use of post-exposure prophylaxis for HIV following sexual exposure’
- 11. BHIVA (2011) ‘ UK guideline for the use of post-exposure prophylaxis for HIV following sexual exposure’
- 12. WHO / ILO (2007) ‘ Post-exposure Prophylaxis to Prevent HIV Infection’
- 13. WHO / ILO (2007) ‘ Post-exposure Prophylaxis to Prevent HIV Infection’
- 14. British Association for Sexual Health and HIV (BASHH) (2011) ' UK guideline for the use of post-exposure prophylaxis for HIV following sexual exposure' International Journal of STD & AIDS 22: 695–708
- 15. WHO / ILO (2007) ‘ Post-exposure Prophylaxis to Prevent HIV Infection’
- 16. WHO / ILO (2007) ‘ Post-exposure Prophylaxis to Prevent HIV Infection’
- 17. BASHH (2006, February) ‘UK guideline for the use of post-exposure prophylaxis for HIV following sexual exposure’, International Journal of STD and AIDS, 17 (81-92)
- 18. Harding, A. (2007, 23rd November) ‘Post-exposure HIV drugs won’t boost risky behaviour’ Reuters.
- 19. IRIN (2007, 1st May), ‘ HIV prevention services miss rape survivors’.
- 20. IRIN (2007, 1st May), ‘ HIV prevention services miss rape survivors’.
- 21. Pinkerton, S.D, Holtgrave, D.R, Bloom, F.R. (1998, 18th June) ‘Cost-effectiveness of post-exposure prophylaxis following sexual exposure to HIV’, AIDS, 12 (1067-1078)
- 22. Tissot, F et al. (2010) ' Nonoccupational HIV post-exposure prophylaxis: a 10-year retrospective analysis' HIV Medicine 11
- 23. Otten. R. A et al (2000, 14th July) ‘Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (Human immunodeficiency virus type 2)’ Journal of Virology, 74, 20 (9771-9775)
- 24. Tsai, C.C. et al (1998, May) ‘Effectiveness of postinoculation (R)-9-(2-phosphonylmethoxypropyl) adenine treatment for prevention of persistent simian immunodeficiency virus SIV infection depends critically on timing of initiation and duration of treatment’, Journal of Virology, 72, 5 (4265-4273)
- 25. Cardo, D.M. et al (1997, 20th November) ‘A case-control study of HIV seroconversion in health care workers after percutaneous exposure’, New England Journal of Medicine 337 (1485-1490)
- 26. Cardo, D.M. et al (1997, 20th November) ‘A case-control study of HIV seroconversion in health care workers after percutaneous exposure’, New England Journal of Medicine 337 (1485-1490)
- 27. Roland, M. et al (2005) ‘Seroconversion following nonoccupational postexosure propylaxis against HIV’, Clinical Infectious Disease, 41 (10)
- 28. CDC (2005, 21st January) ‘Antiretroviral post-exposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States’ MMWR 54 (1-20)
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