Back HIV Prevention Pre-exposure (PrEP) High Effectiveness Seen in English PrEP Trial, All Will Be Offered Truvada

High Effectiveness Seen in English PrEP Trial, All Will Be Offered Truvada


An interim analysis of the English PROUD study data has shown that daily Truvada pre-exposure prophylaxis (PrEP) is highly protective against HIV for gay men and other men who have sex with men (MSM) at high risk of infection. On this basis, the PROUD Trial Steering Committee has announced that participants currently on the deferred arm of the study will be offered the opportunity to begin PrEP ahead of schedule.

[Produced in collaboration with Aidsmap]

The Steering Committee of the PROUD trial of pre-exposure prophylaxis (PrEP) for gay men in England announced today that participants currently on the deferred arm of the study, who have not yet started PrEP, will be recalled to their clinics and offered the opportunity to begin PrEP ahead of schedule. This is because the effectiveness seen in the trial has exceeded the threshold set for trial continuation. [Disclosure: author Gus Cairns is co-chair of the Steering Committee of the PROUD trial.]

Although the exact effectiveness seen in the trial is yet to be established pending analysis and follow-up of participants, the indications are that it is considerably in excess of that originally anticipated by the researchers.  

In PROUD, 545 gay men at high risk of HIV infection have been recruited through 13 sexual health clinics in London, Brighton, Manchester, Birmingham, Sheffield, and York.

Participants have all been offered a package of regular testing for HIV and sexually transmitted infections (STIs), condoms, safer sex support, and behavioral surveys and monitoring, and have been randomized into 2 groups. One group has also received tenofovir/emtricitabine (Truvada) immediately (the "immediate arm") while the other has, up until now, been offered it a year into the study (the "deferred arm").

The object of this design is to establish whether participants who know they are taking PrEP will change their HIV risk behavior -- such as using condoms less or even not using them at all -- and, if so, whether this will reduce or even cancel out the beneficial effect of PrEP.

This trial design is being used because some critics of PrEP have forecast that PrEP will have an overall negative effect. In August, the Chief Executive of the AIDS Healthcare Foundation, Michael Weinstein said: "We want the public to know that the government-sanctioned widespread scale up of PrEP appears to be a public health disaster in the making." It is therefore very important to know if people like Weinstein are right or wrong, and whether PrEP will have a negative effect if people know they are taking it.

The PROUD pilot has not been designed to establish the effectiveness of PrEP as such. At the time it was designed, it was thought that a large trial of 5000 participants would be needed to generate the number of HIV infections required to establish a clear measurement for the effectiveness of PrEP in reducing (or not) HIV infections among participants.

However, in April 2014, it became clear that the offer of PrEP had appealed to a subset of gay men characterized by a higher HIV infection rate than had originally been taken into account when calculating trial size. This implied that the pilot trial would be potentially capable of producing a clear answer on effectiveness, in spite of its small size. An Independent Data and Safety Monitoring Committee (IDMC) was therefore set up. 

IDMCs have a privileged position in randomized trials: they are the only people to see the unblinded data before the end of the trial, and their job is to monitor the data to see if there are signs that the trial should be stopped. Grounds for stopping include that it has become clear that the intervention being tested causes harm, that the trial will never produce a clear result (so-called "futility"), or that the intervention is so beneficial it would be unethical to withhold it from some people in the study. The PROUD IDMC met 3 times, and in the third meeting on October 6 decided that the intervention was clearly beneficial; it found that the effectiveness of immediate PrEP appeared to have passed a threshold they had previously set.

This threshold will not be the actual effectiveness: it is the lowest-possible likely effectiveness allowing for chance results or, in technical terms, the lower bound of the 95% confidence interval. In terms of the actual numbers of infections seen, the observed effectiveness is likely to be higher. The final difference will not become clear until the clinics have recalled as many participants as possible, as there will no doubt be some other previously undetected HIV infections in both groups. Currently 130 people in the deferred arm are yet to be offered PrEP.

Full results are expected early next year.

The PROUD trial has not stopped. It will continue because it is still important to find out longer-terms trends: will participants' adherence to PrEP -- which must clearly have been high -- fall over time? Will levels of risk behavior stay unchanged? Will drug resistance feature to any significant extent?

These are still important questions to answer and the English National Health Service is likely to want them answered before making a decision as to whether to provide PrEP. This development opens up opportunities to study other drugs or regimens too -- but above all, it opens up an opportunity to make a big impact on the HIV epidemic among gay men in the U.K. and elsewhere.



MRC Press Office. PROUD study interim analysis finds pre-exposure prophylaxis (PrEP) is highly protective against HIV for gay men and other men who have sex with men in the UK. Press release. October 16, 2014.