Last month’s British HIV Association (BHIVA) conference heard that providing gay and bisexual men with home packs of post-exposure prophylaxis (PEP) pills cut the average time between possible exposure and starting PEP from over a day to seven hours, but the majority of opportunities for prevention were still missed.
Having emergency packs of PEP pills at home to take after a possible exposure to the virus could be a prevention solution for people who only occasionally have such risks, or don’t want to take daily or regular pre-exposure prophylaxis (PrEP).
Post-exposure prophylaxis - background
PrEP means taking antiretroviral medication before any likely exposure to HIV, either daily or ad-hoc. But post-exposure prophylaxis involves taking antiretrovirals after a possible exposure.
An older idea than PrEP, it started as long ago as 1988 as an emergency course of AZT (zidovudine) for healthcare workers accidentally exposed to HIV. Because the process of HIV infection may already be in its earliest stages and has to be stopped, it needs to be stronger than PrEP, and now usually involves three drugs rather than the two used in PrEP. PEP has never been subject to a randomised controlled trial, as it would be unethical to offer a placebo to someone who might already be infected.
This is also the reason why guidelines still recommend that PEP should be taken as a course of three drugs for 28 days after exposure even though the drug exposure levels observed in PrEP – especially in event-driven ‘2-1-1’ PrEP for anal sex, which already involves taking two post-exposure doses – suggest a shorter course might be sufficient.
Because studies of PEP do not involve placebos, it is hard to demonstrate the efficacy of PEP. A 1997 case-control study of healthcare workers from France, Italy, the UK, and the US came to the conclusion that PEP – which in those days meant AZT monotherapy – reduced the risk of becoming infected with HIV by 81%, and this is the efficacy figure that has been cited ever since.
PEP needs to be started before HIV has migrated to the lymph nodes and has become a systemic infection. Most guidelines recommend that to have any efficacy at all, PEP needs to be started within 72 hours of exposure, and preferably within 24. These time limits were derived from studies using solo tenofovir as PEP in monkeys in the 1990s. The studies also suggested that if PEP was started sooner rather than later, a shorter course might be effective.
In the UK, PEP can be obtained from sexual health clinics and also from accident and emergency departments at weekends when clinics are closed. In the UK it is not supplied by GPs.
PEP has maybe never really been used to its full potential, partly because it still involves a month-long course of three ARVs and partly because it has a limited time window for efficacy but has to be obtained from medical facilities, so is not easily or instantly available.
Studying the ‘HIV morning-after pill’
If ‘PEP packs’ could be supplied to keep at home for prompt use then it could be a valuable additional prevention choice. It could benefit both people who may have exposures to HIV rarely and who do not wish to use PrEP routinely, and people who want a backup prevention method if they have an exposure when they are not fully protected by PrEP (5% of participants in the immediate-PrEP arm of the PROUD study, and 17% overall, also took PEP at least once.)
For this reason Dr Julie Fox and researchers from Guy’s and St Thomas’ and King’s College Hospitals in South London decided to do a study of ‘bathroom PEP’, randomising subjects into two arms who either received PEP packs immediately or after a delay.
This is not the first study of home PEP packs. Back in 2004, Dr Mauro Schechter and colleagues in Brazil reported on a study providing four-day packs of AZT and 3TC (lamivudine) for gay men at high risk of HIV in Rio de Janeiro. Although PEP was not used often enough to make a difference to HIV incidence in the group as a whole, on the individual level Schechter was able to estimate that PEP, when used, reduced the risk of HIV infection by 74%.
Dr Fox said the despite this research, home packs had not been adopted by clinical services. Currently in the UK the average time between HIV exposure and starting PEP was 24 hours and this had not improved since 2006.
The study randomised 135 HIV-negative gay and bisexual men at ‘medium risk’ of HIV, in London, Manchester and Brighton. Half of them received PEP packs immediately and remained in the study for 48 weeks. The other half could access PEP through the usual routes – i.e. having to get it from a sexual health clinic – for 48 weeks, then had PEP packs provided for 24 weeks, so staying in the study for 72 weeks.
‘Medium risk’ meant having condomless anal sex with more than one partner in the last three months, and/or having caught a bacterial STI in the last three months, and/or and any use of PEP in the previous year.
Dr Fox said they did not want to recruit men whose risk would indicate they should start PrEP immediately, though in practice some participants were at high risk.
The packs contained five days of PEP pills. The regimen was a novel one: the standard UK PrEP regimen of tenofovir disoproxil fumarate (TDF) plus emtricitabine in one pill, plus the HIV entry inhibitor maraviroc (European brand name Celcentri) in the other.
Maraviroc is an interesting drug, being the only one of its class, but has struggled to find its place in HIV treatment and prevention.
The fact that it blocks HIV entry into cells suggested it might be useful in PrEP but it is insufficiently potent to be used by itself as oral PrEP or in a vaginal ring. It is thought that because maraviroc attaches itself to host cells rather than the HIV virus, it does not reach high enough concentrations in the body to work as a prevention drug on its own. However it might be exactly the third addition needed for PEP, especially as, because it is rarely used, HIV with resistance to it is rare too. It also has low toxicity: its main reported side effect is postural hypotension (low blood pressure, which can produce faintness or blackouts when standing up) but this was not reported in the present study.
During their time in the study, participants attended every 12 weeks for HIV and STI testing, to fill in a behavioural questionnaire, and to find out whether they had used PEP and, if so, the time from exposure to first dose.
There were 69 men in the deferred arm of the study and 66 in the immediate home-PEP arm. The average age of participants was 30 (though only 14% were under 25), 75% were of White and 7% of Black African ethnicity and 55% had been born in the UK. Only 35% were currently in a long-term relationship.
Fifty-three per cent had had a bacterial STI in the last 12 months and 31% a rectal STI. Thirty-nine per cent had used PEP in the last 12 months, though rather more in the immediate home-PEP arm (46%) than in the deferred arm (33%).
" Possibly the most significant finding was that participants took PEP much less often than their risk of HIV would indicate, and many not at all."
One third (22) of the 66 men in the home-PEP arm actually used a PEP pack (most only once, although six took it two or three times). In contrast less than one in five men (13 out of 69) in the deferred arm sought PEP from their clinic. In the home-PEP arm, four cases of inappropriate use, where a clinic would probably not have advised PEP, were not included in the figures mentioned above.
The average time from HIV exposure to first PEP dose was 7.6 hours in the home-PEP arm (so it really was a 'morning after pill') but 28.5 hours in the deferred-PEP arm. Fourteen out of 22 participants (63%) took home PEP less than 10 hours after exposure, whereas seven out of 13 participants in the deferred arm (54%) took it more than 30 hours after exposure.
There was evidence that the novelty of home PEP, or possibly HIV anxiety, declined in the home-PEP participants; 24 of the 29 home packs were used in the first half of the study. In contrast the demand for PEP in the deferred arm remained steady at three to four requests per quarter.
Possibly the most significant finding of the study, however, was that – as in the 2003 study in Brazil – participants took PEP much less often than their risk of HIV would indicate, and many did not take it at all. The home-PEP participants reported 268 occasions when use of PEP might have been appropriate – PEP was only used after 11% of these. In the deferred arm, there were 474 such missed opportunities for PEP so the 15 times PEP was used only covered 3% of the times it could have been.
The mean number of missed opportunities was thus seven per participant in the deferred arm and four in the home-PEP arm. But the median number of missed opportunities per participant was actually similar in the two arms. The data was skewed, and 75% of the participants who indicated more than ten missed opportunities for PEP were in the deferred arm. The number of new STI diagnoses was similar (27 in the home-PEP arm versus 31 in the deferred arm).
There was one new HIV infection, in the deferred arm. Dr Fox commented that that this person “had repeatedly been advised to start PrEP due to high-risk behaviour”. But the fact that this was the only infection in 231 person-years of observation highlights the currently low rates of HIV infection, which make it harder than ever to measure the efficacy of PEP, especially in small studies.
Dr Fox commented: “Further work is needed to understand in which settings and in whom home PEP would be most appropriate or acceptable.” However, she said, home PEP could be a useful emergency tool for situations of unexpected risk or for people who for one reason or another don’t want to or can’t take PrEP.
Fox J et al. Self start HOME HIV Post exposure prophylaxis (PEPSE), to reduce time to first dose and increase efficacy: an RCT. BHIVA Spring conference, Manchester, 2022. Abstract #O1.