Substantial differences between European and new US PEP guidelines

The United States government’s public health guidelines on the use of non-occupational post-exposure prophylaxis (PEP), which were announced last week, differ from the existing European guidelines in three main areas. These include the situations after which PEP is recommended, the estimated risk of HIV transmission and the choice of drugs to be used.

Non-occupational PEP (NPEP) is the use of antiretroviral drugs to prevent HIV infection after non-occupational exposure to the virus. This can be through unprotected sex, sexual assault, unsafe injecting practices, accidents or bites.

Both sets of guidelines state that PEP should be given to HIV-negative people who have been exposed to potentially infectious body fluids from a person known to be HIV-positive, and where the exposure poses a substantial risk of exposure. They also agree that antiretroviral therapy be given for 28 days, in order to prevent HIV infection from taking hold within the body.

The United States guidelines recommend PEP when the source person is known to be HIV-positive. When the HIV status of the source is not known, they recommend that it should be given according to the judgement of a clinician.

In contrast, the European guidelines are more specific in when PEP should be used if the source's HIV status is not known:

• It is recommended following potential exposure during receptive anal sex with a person from a group or area with high HIV prevalence (over 15%).
• It should be considered following anal, vaginal or oral sex with ejaculation with a person from a group or area with high HIV prevalence.
• If the source is not from a group or area with high HIV prevalence, NPEP is only recommended following exposure during receptive anal sex.

There are also differences between the risks of transmission cited in the two sets of guidelines. For example, the risk of transmission through receptive anal sex is estimated at being 0.5% in the American guidelines. However, the European guidelines are based on an estimated risk of 3%.

Writing in Eurosurveillance Weekly, representatives of the European Project on Non-Occupational Postexposure Prophylaxis for HIV (Euro-NONOPEP) write: “This large difference in transmission risk may have influenced the recommendations made for PEP usage… As long as there is uncertainty as to the true risk of transmission via different exposures, it is difficult to reach consensus on all the situations where PEP should be prescribed.”

Finally, the guidelines differ in the recommended antiretrovirals to be used. The United States recommendations state that a combination of two nucleoside reverse transcriptase inhibitors (NRTIs) is sufficient, since there is no evidence for the increased effectiveness of three drugs.

In contrast, European guidelines recommend triple therapy consisting of drugs from two different classes, although two-drug therapy is a possible option. “The United States guidelines…place a heavier emphasis on the possible risks of side-effects and state that these should be discussed with the patients,” writes Euro-NONOPEP.

Euro-NONOPEP stresses that different countries should share their data and recommendations in order to build up an evidence base on which to build future guidelines for this difficult area. This is being achieved through their establishment of an international study to analyse cases of high-risk exposure to HIV and a large-scale systematic review on NPEP.

However, the organisation also acknowledges that the results of a number of studies have been published since the development of the European guidelines. “These studies, and the recent publication of the United States guidelines, have highlighted the need to revise and update the Euro-NONOPEP and other national guidelines,” it concludes.