large-scale prospective, placebo-controlled trials have not been carried out
for PEP, a definitive answer regarding its effectiveness cannot be given, but
experience from several PEP programmes has been recorded in a number of
in San Francisco1
investigated the safety and acceptability of PEP after possible sexual exposure
to HIV or exposure involving injecting drug use (IDU). Individuals who had experienced exposure
within the previous 72 hours were offered one month's treatment with Combivir.
Other drugs, ddI (didanosine, Videx) and d4T (stavudine, Zerit),
were offered in cases where there was a risk of exposure to AZT- or
401 requests for PEP were received between December 1997 and March 1999: 91% of
participants were men and the median age was 32 years.
majority (93.5%) of the participants sought PEP because of sexual exposure and
only 2% reported sharing of IDU equipment. Receptive anal intercourse was
reported in 40% of the exposures.
that the source partner was HIV positive was expressed by 174 (43%) of
participants. When exposure was sexual, it usually represented a lapse in safe
sex practices rather than habitual high-risk behaviour.
adherence to medication (in the four days before a clinic visit) was reported
by 84 to 78% of participants, despite high levels of side-effects, including
nausea, fatigue, headache and diarrhoea.
rates were high at 78%. This was most likely due to the provision of one-to-one
medication adherence counselling, and to dispensing only a limited supply of
medications at each visit - which required individuals to make regular contact
study was not powered to evaluate efficacy, though no individuals were observed
to develop antibodies to HIV at six months after exposure.
study in San Francisco
evaluated 702 subjects who had taken PEP after sexual exposure (including some
of the subjects enrolled in the study discussed above). The evaluation took
place twelve weeks after exposure. Three people seroconverted despite reporting
no further sexual exposures after starting PEP, and so are probably evidence of
PEP failure. In addition, four people became HIV-positive despite PEP but there
were either additional exposures to HIV, or HIV was found in blood specimens
given at the start of PEP (meaning subjects were already infected with HIV and
did not know it).
course, given that the chance of contracting HIV from a single occasion of
receptive anal intercourse is in the region of one chance in 30 to one in 250,
many of the men taking PEP would not have seroconverted anyway. Because of
this, among 702 men one would only expect about six infections if they only had
one risky encounter each. But because only three became infected who had
definitely only had one encounter, the study implies that PEP prevents at least one in
average time delay between the sexual exposure and taking PEP was 32.5 hours,
but among men who became HIV-positive it was 45.5 hours (nearly two days) lending
support to the view that initiating PEP within a day of exposure ensures it has the
best chance of working.
Michelle Roland said that the four men who went on to have unsafe sex soon
after taking PEP were a reminder that it could not be a stand-alone prevention
method: “It provides an important HIV prevention opportunity when exposed
individuals may be especially receptive to assistance with reducing their HIV
risk...but is only one part of that prevention activity. Sexual exposures are
usually not isolated, and helping people stay HIV negative requires response to
both the presenting exposure and attempts to reduce subsequent exposures.”
the most conclusive studies of PEP was conducted in Brazil and reported at the 2002 Conference
on Retroviruses and Opportunistic Infections (CROI).3
Here, 202 HIV-negative gay men were enrolled and followed for an average of two
years. At the time of enrolment, 57% of the group reported “high-risk
behaviour”. PEP, consisting of four weeks of AZT/3TC, was used 100 times by 73
(36%) of the participants, 91% of whom completed the course. Most men took it
just once or twice during the two years of the trial, but one man took it nine
were 11 seroconversions among the group; however, only one occurred in someone
who had taken PEP. Analysis of the strain of HIV that infected him despite
using PEP showed that it had the M184V mutation (associated with resistance to
researchers calculated that PEP, on the occasions it was taken, reduced the
seroconversion rate by 83%, from 4.1 cases per 100 patients a year to 0.7 cases
when men did take PEP.
the study also found that there was almost no difference in the infection rate
observed in the study population as a whole (2.9 cases per 100 patients a year)
and what would have been expected if PEP had not been available (3.1 infections
per 100 patients a year). This was because PEP was not taken nearly often
enough to make a difference to HIV incidence in the group as a whole. Although quite a
high proportion of the study population took PEP, they were bad at evaluating
risk and did not always take it when needed.
reasons PEP was not taken were either that the men mistakenly assumed their
partner was faithful and HIV-negative, or that they caught HIV through routes
they considered low risk, such as oral sex.
seems to bear out findings from the UK about gay men’s estimation of
risk. The 2004 Gay Men’s Sex Survey, Risk and Reflexion,4
found that gay men tend to see sexual risk in terms of risky actions rather
than risky partners. Their focus was on condoms or different sexual acts
rather than the HIV status of their partner. Sigma Research, which conducted
the research, comments that this gives an insight into where men go wrong in
evaluating risk: “The problems seem to be more with misreading the presence of
HIV infection (exposure) than underestimating the potential for transmission
when it is present.”
Brazilian study highlighted one of the central dilemmas of PEP. Unlike other
interventions, its availability may be crucial to individuals who need it but,
as an emergency measure only used by a minority of gay men, it is unlikely to
make much difference to HIV incidence on a population level. This has led to
controversy about exactly how much it should be promoted as a prevention method
– see more below.
because people seeking PEP are highly motivated to avoid infection, this may be
a time when education and counselling will have significant influence.
other interesting findings came from the Brazilian study. One was that
“high-risk” behaviour declined during the study from 56 to 40%. Although it has
been suggested from other studies that people reporting declines in risky
behaviour may sometimes not be reporting the whole story due, possibly, to
guilt at being a ‘study failure’, this finding may help allay fears that the
widespread availability of PEP for sexual exposure will cause an increase in
92% of the time, PEP was taken appropriately, i.e. after an exposure that
researchers considered high risk. This seems to offer a degree of assurance
that PEP will not be abused by the ‘worried well’ concerned by very low-risk
the study issued people with ‘starter packs’ – ready-wrapped doses of AZT/3TC
with instructions that participants should take them immediately following
exposure. Other PEP schemes have relied on people reporting to A&E
departments after sexual exposure. Since one of the key components to
successful PEP is prompt treatment (ideally within 24 hours) this may explain
some of the difference between the reported effectiveness rate of 83% in the Brazil study and the 53%
rate in the cost-effectiveness study detailed in the following section.
Even failed post-exposure prophylaxis may have some
effect. A study in 2008 suggested that unsuccessful PEP may still result in
weaker HIV infection and lower viral load.5
Although this is only a case report, it does follow reports of similarly
suppressed HIV viral loads in monkeys who were infected with HIV in studies of pre‑exposure prophylaxis.
The case report involved a patient who received PEP
with Truvada a fixed-dose combination pill containing FTC and tenofovir.
Although this treatment failed to prevent HIV infection, the patient did have a
well-preserved immune function and a lower viral load than would be expected.
He was therefore much less infectious than the average patient during acute
The 38-year-old New York gay man first came to a
clinic on 26 September 2006 reporting that he had had unprotected receptive
anal sex with multiple partners during the previous 48 hours. He was treated
with Truvada but during the period on this treatment, on 24 October, he reported
more episodes of risky sex, and his course of PEP was therefore extended. He
stopped taking it on 7 November and tested HIV-negative on that date.
He reported a third episode of risky sex on 28
November and was restarted on Truvada. On 18 December, three weeks
later, he tested HIV-positive. He was adamant that he had had no risky sex
during the period when he was not taking post-exposure prophylaxis, which he
finally stopped taking after he
tested HIV positive, on 29 December.
His first two viral load tests were performed on 22
December (when he was still receiving treatment with Truvada) and on 9
January 2007. His viral load was very low, with 213 and 647 copies/ml in these
two tests respectively. His viral load increased after this but never exceeded
3500. His CD4 count was a very high 1800 cells/mm3 on 22 December,
just after his first positive HIV antibody test, and then fell to about 750. At
no time did he have the high viral load and low CD4 count typical of acute HIV
infection, and he had no HIV seroconversion symptoms.
The patient's antibody response developed much more
slowly than normal. Some basic tests were performed on his HLA genes, which
determine susceptibility to HIV infection, but he had no genetic mutations
associated with a lower viral load or less virulent course of HIV infection.
One theory of how HIV causes AIDS is that the initial
destruction of CD4 cells and immune hyperactivation in the gut, from which the
body never completely recovers even under HIV therapy, eventually depletes the
immune system. However tests suggested that this man’s gut immune system was
better preserved than in other cases of acute infection. It is possible that
disease progression may therefore be slower.