Post-exposure prophylaxis (PEP) is a four-week course of medication
that may block HIV infection after exposure to the virus. You can read an
overview of PEP here. PEP should not be confused with pre-exposure
prophylaxis (PrEP), which involves taking
medicine on an ongoing basis, before
possible exposure to HIV.
The most accurate way to test the efficacy of PEP
would be to conduct randomised trials comparing people taking PEP with people
not taking PEP. However, this has never been considered to be ethically
acceptable as it would involve denying people who have been exposed to HIV a
treatment that was expected to be effective. As a result, almost all the
evidence on the effectiveness of PEP in humans comes from observational studies,
which provide a less robust form of evidence. However, these studies indicate
that PEP is highly effective.
In 2016, the Centers for Disease Control and
Prevention (CDC) in the United States reviewed six observational studies of PEP
use by gay, bisexual and other men who have sex with men. The six studies, from
the United States, Australia, the Netherlands and Brazil had been published
since 2004.
Of the 1535 men who took PEP, 1487 remained HIV
negative and 48 men acquired HIV. However, the details of the transmissions that
did occur are important.
- In 40 cases, HIV
infection was attributed to ongoing risk behaviour after completing PEP. Among
these 40 are 35 cases in which seroconversion occurred more than six months
after starting PEP. These HIV transmissions are unlikely to be due to a failure
of PEP.
- 8 cases are
considered to represent potential PEP failures. This equates to 5.2 transmissions
per 1000 PEP users (0.5%).
Even among these eight cases it is not certain
that PEP failed. In three cases, very few details of the cases were recorded by
researchers. Another four were diagnosed with HIV between three and six months
after starting PEP, but no information on their sexual behaviour after
finishing PEP was reported – it is possible that they acquired HIV due to
further risky sex after completing PEP. One case might be due to a strain of
HIV that was resistant to a drug included in the man’s PEP regimen.
The CDC identified a further 15 studies in other
populations, including adults, adolescents and children. They may have been
exposed to HIV through consensual sex, sexual assault, injecting drug use or needlestick
injuries, depending on the individual study.
Of the 2209 people who took PEP, 2190 remained
HIV negative and 19 were diagnosed with HIV.
- In 18 cases, HIV
acquisition could be explained by factors such as poor adherence or ongoing
risk behaviour.
- One case was
attributed to PEP failure. This relates to a woman who began PEP within four
hours of being sexually assaulted and completed the 28-day course, but
seroconverted to HIV six weeks after starting PEP.
PEP is also used by healthcare workers, after needlestick
injuries. The first evidence of PEP efficacy came from a case-control
study in 1997 which showed an 81% reduction in the odds of HIV transmission
among healthcare workers who received zidovudine as PEP. Whereas there were 57
confirmed HIV infections among American healthcare workers believed to be
due to occupational exposure between 1985 and 1999, there was only one further
case between 2000 and 2013. The reduction in infections was attributed to the
greater use of PEP as well as effective treatment of people with HIV and staff
training to prevent injuries.
These data are corroborated by animal studies. A
meta-analysis, published in 2015, reviewed 16 studies in which one group of primates were exposed to HIV or
SIV and then given PEP, with another group exposed but receiving no treatment.
The risk of infection was 89% lower among animals given PEP compared with those
that did not receive PEP.
In summary, decades of experience has shown PEP
to be associated with a substantial reduction in HIV acquisition following condomless
sex and needlestick injuries. Where there have been HIV infections in people
receiving PEP, these are primarily related to:
- Not starting PEP
promptly
-
Missing doses of PEP
or not finishing the 28-day course
-
A viral strain
that is resistant to drugs used in PEP
-
Use of
antiretroviral drugs which have sub-optimal penetration of the genital tract (these
drugs are no longer recommended)
-
Having unprotected
sex, with further exposure to HIV, while taking PEP.