The pilot stage of the PROUD study – the UK's study of HIV pre-exposure prophylaxis (HIV-negative people taking HIV drugs to prevent HIV) in gay men – is now fully enrolled, the trial's Community Engagement Group announced yesterday. As of Monday 7 April, the trial reached its target of 500 participants (in fact enrolling 525).
The trial investigators have applied for funding to expand PROUD into a full-scale efficacy trial with 2300 participants. A final decision on this is expected in November, meaning that any expansion will not start recruiting until spring 2015.
This means that, in England, pre-exposure prophylaxis (PrEP) will not be available, other than by private prescription, to anyone else until then. Resources are currently being sought so that current participants do not have to start coming off PrEP in November this year unless they wish to and can continue receiving it until the full study opens, if it does.
The PROUD study
Last week’s joint conference of the British HIV Association (BHIVA) and the British Association for Sexual Health and HIV (BASHH) heard the first data from the study, namely the baseline data on the demographic make-up and risk behaviour of the participants. These data from PROUD were presented by investigator Dr Monica Desai of Public Health England.
PROUD (which stands for PRe-exposure Option for reducing HIV in the UK: an open-label randomisation to immediate or Deferred daily Truvada for HIV negative gay men) started enrolling in November 2012, after the US Food and Drug Administration licensed Truvada (tenofovir/FTC) once daily as PrEP in the USA in July 2012.
PROUD is a two-year study with participants randomised either to take Truvada daily for two years or to take it only during the second year. Full results from the pilot study will therefore not be available until summer 2016, unless the statisticians monitoring the trial detect a result that is so strongly positive or negative it can be stopped early.
Unlike the iPrEx study, which established the efficacy of PrEP in gay men, PROUD is an open-label study, meaning that no one gets a placebo. As well as potentially being able to measure the efficacy of PrEP in a much more ‘real world' setting than that of a placebo-controlled trial (due to its small size, the PROUD pilot is not designed to provide a definitive answer on efficacy), the advantage of the open-label deferred-versus-immediate study is that, because all those taking PrEP know they are on active drug, the trial can take a true measurement of whether people change their sexual risk behaviour once they know they are taking PrEP.
Who joined and their HIV risk
The average age of the 443 participants with data was 35.5 years; a quarter was aged 29 or below and another quarter 42 or above. Eighty per cent of participants were white: 4% (14 individuals) black, 6% (27) south Asian and 10% (48) of other ethnic background. Nearly 60% were graduates and three-quarters had UK education to 18 (of the remainder, some had overseas qualifications): only 3% of participants were early school leavers.
It was possible for HIV-negative seroconcordant partners to enrol in PROUD together and be randomised to the same arm: there were 17 co-enrolled pairs in the study, and one triplet.
Participants reported a median of ten anal sex partners in the last three months. They reported having receptive anal sex without a condom with two partners and insertive anal sex without a condom with three, so at baseline they were using condoms with at least 50% and probably more of their partners.
Of participants’ partners, 23% were of unknown HIV status. Of the rest, 44% were known or assumed to be HIV negative. Of the one-third who were known to have HIV, 81% were known to be taking HIV treatment, 12% were known to be not on treatment (4% of all partners) and 7% were of unknown treatment status.
Participants were asked why they didn’t use condoms when they didn’t. Most gave several different reasons. The most common reason was “It’s much more enjoyable without a condom” (given by two-thirds of participants), “I don’t like using condoms” (half of them) or “My partner doesn’t like using condoms” (a third of them). Approximately a quarter each said that condoms weren’t discussed, that sex happened under the influence of drugs or alcohol, or that they didn’t consider that that particular sexual encounter risked HIV (e.g. it was with a long-term partner known to have recently tested negative). Seventeen per cent (74 individuals) said they had a ‘negotiated safety’ agreement with their partner whereby they used condoms with others but not their main partner.
No fewer than 40% of participants had used post-exposure prophylaxis (PEP) in the last 12 months before joining the study and 21% had used it more than once.
STIs, hepatitis and drug use
Participants reported high levels of bacterial STIs (sexually transmitted infections) in the previous 12 months. A quarter each reported having had rectal, oral or urethral gonorrhoea (individuals could have two or all three of these); about 15% reported urethral and/or oral chlamydia; 10% reported syphilis and 9% genital warts.
In contrast only 0.5% reported hepatitis C and 0.3% hepatitis B.
However, in a separate presentation, Dr Juan Tiraboschi of Guy’s and St Thomas’s Hospital Trust reported that, during PROUD, five participants so far have been diagnosed with acute hepatitis C (HCV), even though there has not been systematic HCV testing. Two of these men had partners with hepatitis C and one reported injecting drug use; only one had symptoms that prompted testing.
The PROUD participants reported high levels of drug use: two-thirds had used nitrites (poppers) in the last 12months, 57% erection drugs such as Viagra, half mephedrone or similar, 43% GHB, 35% cocaine and 24% methamphetamine.
Trial participants' opinions on where to go next
The second participants' feedback meeting of the trial was held in London on 10 March, attended by 17 trial volunteers from six clinic sites. The purpose of this meeting was particularly to get volunteers' opinions on further research options now the pilot trial was nearing full enrolment.
Participants had a number of different opinions on possible research, but several emerged that had a fair degree of unanimity:
- Participants had felt comfortable with taking PrEP daily and had felt no personal need for alternative dosing options, though they acknowledged that alternative options might be more attractive to some other people.
- They were concerned that intermittent PrEP, and particularly PrEP taken only before and after sex, might be more difficult to remember to take, especially for people with irregular lifestyles. They also felt that daily PrEP incorporated some 'forgiveness' for missed doses.
- They were interested in alternatives to Truvada, but only if they were at least as effective. They were opposed to a placebo-controlled trial of any new drug and felt that Truvada, blinded or unblinded, should be the comparator.
- They were intrigued by the idea of injectable PrEP, but were concerned about side-effects and about whether people would start feeling insecure about whether they were still covered by PrEP towards the end of the month.
- No-one had heard of rectal microbicides. They did not see a microbicide as a useful alternative to oral PrEP, because it had to be used during sex, but some did think it might be a useful adjunct to PrEP if incorporated into lubes, especially if provided at gay saunas and similar venues.
- There was a lot of discussion about the stigma related to being on PrEP. People wanted support to be able to articulate their use of PrEP in a positive way, as an empowered statement of taking control of their health. A few participants had had negative experiences with healthcare professionals, as with one who talked of Truvada as toxic.
- There was support for a private participants' online forum for support purposes, but little for a public social media group, for reasons of stigma and privacy.
Dolling D, Desai M et al. Who accesses PrEP? An analysis of baseline data in the PROUD pilot study. Third joint BHIVA/BASHH Conference, Liverpool, abstract 043, 2014.
Tiraboschi J et al. Acute hepatitis C in the PROUD pilot study. Third joint BHIVA/BASHH Conference, Liverpool, abstract 045, 2014.
See http://www.bhiva.org/documents/Conferences/2014Liverpool/AbstractBook2014.pdf for conference abstracts.
- Gus Cairns is co-chair of the Steering Committee of the PROUD Trial.