The limits of PEP: saturation knowledge does not mean saturation use

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Knowledge of post-exposure prophylaxis (PEP) among HIV-negative gay men in Sydney, Australia, has reached virtual saturation point, with 97% aware of it, a study presented at the Sixteenth International AIDS Conference in Toronto reveals (Grulich).

However, the study also reveals that near-universal knowledge has not translated into universal use after HIV risk incidents. Just under a quarter incidents of the very highest-risk, namely unprotected receptive anal intercourse with a positive partner, resulted in men seeking PEP.

Some of the reasons gay men may do not use PEP after risk incidents were highlighted by another study from Toronto of so-called ‘Easy PEP’ (ePEP) which gave gay men ‘starter packs’ of tenofovir/FTC (Truvada) (Cretic). In this study gay men used their starter packs after 26% of cases of unprotected anal intercourse.


post-exposure prophylaxis (PEP)

A month-long course of antiretroviral medicines taken after exposure or possible exposure to HIV, to reduce the risk of acquiring HIV.

unprotected anal intercourse (UAI)

In relation to sex, a term previously used to describe sex without condoms. However, we now know that protection from HIV can be achieved by taking PrEP or the HIV-positive partner having an undetectable viral load, without condoms being required. The term has fallen out of favour due to its ambiguity.

risky behaviour

In HIV, refers to any behaviour or action that increases an individual’s probability of acquiring or transmitting HIV, such as having unprotected sex, having multiple partners or sharing drug injection equipment.


The transition period from infection with HIV to the detectable presence of HIV antibodies in the blood. When seroconversion occurs (usually within a few weeks of infection), the result of an HIV antibody test changes from HIV negative to HIV positive. Seroconversion may be accompanied with flu-like symptoms.



A detailed research plan that describes the aims and objectives of a clinical trial and how it will be conducted.

However young gay men (under 25) were better at using PEP: a slim majority of them used PEP after unprotected anal intercourse.

The first study was of the HIM cohort, a group of 1,427 HIV-negative gay men enrolled between June 2001 and December 2004 via community venues in Sydney. Researchers conducted one phone and one in-person interview a year about their sexual behaviour and HIV risk factors. The yearly interviews have included asking cohort members if they knew about PEP and had ever received it.

Baseline knowledge of PEP was already high in 2001, with 79% of participants being aware of it following the PEP-NOW campaign that year (see this article for more). However, by 2004 this had risen to near-saturation level with 97% of participants being aware of PEP. This may be higher than the level of knowledge in the gay community at large, as HIM cohort members are informed and motivated enough to put themselves forward for research, but this still implies very high levels of knowledge of PEP in the gay community.

In contrast, as we were reminded by another poster at Toronto (Dodds), the United Kingdom has a lot of catching up to do: after the Terrence Higgins Trust’s campaign on PEP, levels of knowledge in the annual UK Gay Men’s Sex Survey (GMSS) increased from 24% in 2003 to 40% in 2005.

A comparatively large proportion of the cohort had used PEP, too: 6% a year, compared with 1% ever in the GMSS.

However, the question must be, why didn’t even more men use PEP, considering this high level of knowledge? PEP was being sought appropriately and men graduated their level of use accurately according to the perceived risk. For instance, 1% of men sought PEP after incidents involving no anal sex but 10% sought it after unprotected anal intercourse (UAI) with a casual partner and 26% sought it if the partner was known to be HIV-positive (all these figures are annual incidence, i.e. the proportion who sought PEP within the last year).

People did seek PEP a lot less often with regular partners: whereas 11% of those who had had UAI with casual partners of unknown HIV status sought PEP, only 5% of those who had had UAI with regular partners of unknown status sought it, and only 18% of those who knew their regular partner was positive.

In terms of the type of anal sex, 8% sought PEP when they had been the active partner in casual sex, 9.8% when the passive partner without ejaculation, but 23% when a casual partner had ejaculated inside them.

In an interesting contrast when it came to regular partners 8% sought PEP when they had been the passive partner without ejaculation, but only 4% when ejaculation had occurred, suggesting that when regular partners do go “that far”, conscious and willed risk-taking may be involved.

Use of PEP was not associated with any change, either positive or negative, with subsequent sexual risk behaviour with either regular or casual partners.

By the end of 2005 there had been 42 seroconversions among the HIM cohort participants, giving an overall HIV incidence of 1% a year (in the UK, the last estimate of incidence among gay men attending GUM clinics – who may be a higher-risk group – was 3% a year in 2004).

However use of PEP was not associated with reduced incidence: rather the opposite. Ten men who had ever sought PEP seroconverted, yielding an annual incidence among this group of 3% a year.

This doesn’t mean that PEP, when taken, didn’t work, but that, as the figures suggest, the men were also involved in HIV risk incidents (indeed a majority of incidents) where they didn’t seek PEP.

So why, despite saturation knowledge, do gay men still not use PEP? A study from Canada looked at reasons for not using PEP after a risky episode.

This small study used the concept of giving men three-day “starter packs” of Truvada to take in case of a risk episode. The participants were gay men aged 18-60 who were not in a monogamous relationship and reported unprotected anal sex at least once in the last six months but less than once a week. They had access to the starter packs for six months and were told to call researchers via a 24-hour helpline if they initiated PEP. They then got the remaining 25 days of PEP from their clinic.

The starter packs were withdrawn after six months but participants were followed for an additional three months to chart any further changes in behaviour or PEP use.

The subjects were split between a youth group of 23 men aged below 25 and an adult group aged 25 and over.

Sexual risk behaviour declined in both groups during the study from two-thirds of participants reporting sexual risk behaviour at baseline to less than half at nione months. The youth group had higher baseline rates of sexual risk with nearly three-quarters reporting risk behaviour at baseline, but their risk behaviour delined more during the study, to around 45%. However whereas adult risk behaviour continued to fall after the PEP packs were withdrawn, among youth it rose again and stood at 60% at nine months.

Nearly all the adult group (89%) reported at least one episode of UAI during the study but fewer of the youths (73%). Furthermore the youth were better at using PEP; nearly half (47%) of incidents of UAI were accompanied by PEP use in the youth group compared with only 29% of incidents in the adult group. However only a third of participants said that the availability of PEP had changed their sexual behaviour (in either direction) by the end of the study, though this proportion did increase as the study went on.

There was a high rate of seroconversion in the study; five men (three youth and two adults) became infected during the nine months, yielding an annual incidence of 11%. Four of the five never used PEP and the fifth did not use it during the three-month period he became infected.

So why did the men not take the pills in their bathroom cabinet after a risky episode? The poster supplies a revealing list of reasons:

  • “I just have a feeling about which partner I can trust”
  • “I’m not at risk because my partner gets tested”
  • “I’m lucky and probably won’t get HIV”
  • “I was in love with him and didn’t want to think about it”
  • “It wasn’t risky because it was very brief”
  • “Pulling out is relatively safe”
  • “As long as my partner does not cum in me I can be certain I won’t get infected”

One of the five took PEP twice but still became infected: he was a heavy drinker and took PEP after two incidents of blacking out at a bathhouse and coming to ‘with memories of being barebacked’. He did not take PEP the third time this happened because he ‘didn’t think anything risky had happened’ and then seroconverted.

Since only one of the people who seroconverted said they had changed their sexual risk behaviour during the nine months, this study may document the limits of that a purely biomedical prevention intervention can do for ‘high-risk’ gay men without additional cognitive or behavioural help.

Two other studies of PEP (Mayer, Lunding) showed better results. In March 2005 the HIV clinic in Boston switched its PEP combination to Truvada from Combivir (AZT/3TC). Since then 57 people have taken it, the same number as in the Canadian strudy, but with no seroconversions (and lower rates of side effects than with Combivir).

PEP has been available in Denmark since 1998, and the country operates a registry documenting every prescription. So far PEP has been prescribed 257 times, and to eleven individuals more than once. Only one seroconversion during PEP has been documented, of a gay man who started PEP 15 hours after the risk incidents and completed his course, but who later admitted to having risky sex again during the period he was on PEP.

Denmark’s guidelines state that PEP can only be prescribed within 24 hours of the risk incident, and the average length of time is only 10 hours; in the UK, where guidelines say it can be prescribed within 72 hours, the average waiting time is 23 hours.

Lastly, there was a presentation (Ende) from somewhere where PEP is much more patchily documented and offered: New York State. PEP has been available in hospital emergency departments since December 2004 but New York guidelines state that the source partner musthave HIV and that PEP will only be prescribed within 36 hours of exposure. A survey revealed that only 60% of hospitals have a protocol for prescribing PEP after what is called ‘voluntary sex’ (i.e. not sexual assault). PE was prescribed two-thirds of the time after a report of sexual assault but only 43% of the time after voluntary sex. Thirty per cent of emergency departments, despite the state guidelines, did not prescribe PEP, only a third follow-up patients and only 23% review seroconversion rates.


Creticos C et al. Feasibility of easy post-exposure prophylaxis (PEP) for HIV prevention in high-risk men. Sixteenth international AIDS conference, Toronto, abstract THPE0449, 2006.

Dodds C et al. Accessing post-exposure prophylaxis (PEP) after sexual risk: the experiences of homosexually active men in England. Sixteenth international AIDS conference, Toronto, abstract TUPE0437, 2006.

Ende AR et al. Non-occupational postexposure prophylaxis for sexual exposures to HIV in New York State emergency departments. Sixteenth international AIDS conference, Toronto, abstract TUPE0435, 2006.

Grulich A et al. Non-occupational post-exposure prophylaxis against HIV (NPEP) and subsequent HIV infection in homosexual men: data from the HIM cohort. Sixteenth international AIDS conference, Toronto, abstract TUPE0434, 2006.

Lunding S et al. Danish postexposure prophylaxis (PEP) registry: use and failure of antiretroviral chemoprophylaxis following sexual exposure to HIV. Sixteenth international AIDS conference, Toronto, Abstract TUPE0433, 2006.

Mayer K et al. Tenofovir-based regimens for Non-Occupational Post-Exposure Prophylaxis (NPEP): improved tolerability and adherence compared to AZT-based regimens. Sixteenth international AIDS conference, Toronto, Abstract TUPE0432, 2006.