PROUD was meant to be a pilot study, exploring the feasibility of conducting a full-scale trial to measure the effectiveness of oral PrEP among gay men, other men who have sex with men (MSM), and transwomen in the UK. It was attempting to test how well PrEP might work in a “real world” setting as opposed to a clinical trial setting. For example, instead of going in for visits to a research site every month, participants went in to a clinic every three months as is recommended by most PrEP guidance. It was also an open-label study, meaning all participants received Truvada; none received a placebo. So participants knew they had the actual drug, and they knew what we all know from studies to date: that it works relatively well when taken daily.
As a pilot study, PROUD recruited 545 participants who were deemed to be at risk of HIV and who were interested in starting PrEP, and randomized them to two arms. Both arms received the same standard prevention package that is currently recommended for anyone: regular screening for STIs and treatment of STIs as needed, risk reduction counselling, provision of condoms. Plus they provided post-exposure prophylaxis (PEP) as needed. In the “immediate” arm, participants started PrEP from the beginning of the study. In the “deferred” arm, participants would receive the same prevention package, but would only start PrEP after a year.
In October 2014, the researchers decided to offer PrEP to participants in the “deferred” arm because a regularly scheduled review of the data available up to that point showed the PrEP significantly reduced risk of acquiring HIV among participants in the “immediate” arm. This was surprising because this was only meant to be a pilot study to see if it was feasible to conduct a larger study (estimated to require 5,000 participants over a few years) to find out how well PrEP works. The fact that there was such a clear sign that PrEP works really well among only 545 participants in such a short period of time was indication of one or more of the following: 1) PrEP worked really well; 2) Participants were adhering really well; and/or 3) Participants were at really high risk. It turns out that it’s all three—see below.
Findings in a nutshell
Participants in the “immediate” arm of the study were 86% less likely to become infected with HIV than participants in the “deferred” arm. This is based on the fact that there were 22 infections among trial participants: three in the “immediate” arm (equivalent to 1.3 infections per 100 person-years), and 19 in the “deferred” arm (equivalent to 8.9 infections per 100 person-years). So far there does not seem to be a significant difference in the rates of other STIs between the two arms, nor in the rates of condom use. However, the full analysis remains to be done. Like previous studies, there were minimal concerns about side effects and drug resistance.
For more complete results, check out these resources:
Holy crap! That is the highest effectiveness rate of any PrEP study to date, along with Ipergay (see separate article) which coincidently also showed an 86% reduction in HIV risk. That is probably due to what seems like very high rates of adherence among PROUD participants—much higher than in most other PrEP studies.
So why were adherence rates so high in PROUD compared to other studies? Perhaps this is due to the fact that: 1) participants knew they were getting actual Truvada, compared to knowing there was a 50% chance of getting a placebo, as was the case in typical efficacy trials; 2) participants had a good sense of how well PrEP works when taken daily, based on the results of other studies.
Perhaps they also recognized that they are at high risk of HIV. Which brings me to the biggest HOLYCRAP! related to this study, as far as I’m concerned. The participants not on PrEP acquired HIV at a rate of 8.9 per 100 person-years. That is remarkably high. Like kind of crazy, really. If I understand this correctly, it means that if you followed 100 HIV-negative people from this cohort for a year, you would expect 9 of them to be HIV-positive by the end of the year.
The participants were on average 35 years old. By my calculation, if we follow 100 of these 35-year-old participants, 37 of them will be HIV-positive by the time they are 40 years old. By contrast, if we followed the same group but added PrEP to their prevention package, among those same 100 HIV-negative men who are 35 years old, 6 of them would be HIV-positive by the time they are 40 years old.
And that’s in a group that is getting tested and treated for STIs, is regularly receiving condoms and risk reduction counselling, and is accessing PEP at very high rates. In the deferred arm, 83 participants (nearly one-third of all participants in that arm) received a total of 174 PEP prescriptions. This is also a group of predominantly white, highly educated, employed, gay-identified men mainly in their mid-30s. There is lots of evidence that incidence rates are even higher in other demographics.
PROUD shows us that it is possible to identify cohorts of very high risk gay men who are interested in PrEP and who will use PrEP at relatively high adherence rates, leading to a very significant reduction in their risk of HIV. Could similar results be achieved with younger gay men, and gay men of colour? A number of demonstration projects currently running in the US should provide answers soon. Do these results really apply to transwomen? With less than half a dozen PROUD participants identifying as transwomen (and less than 30 in iPrEx), it is probably safe to say that more research is needed in this population.
Meanwhile, we have our own demonstration project in Canada. PREP-5 is a PrEP pilot study among 50 gay men at high risk of HIV in Toronto. The study is being conducted by Dr. Darrell Tan from St-Michael’s Hospital. Need I mention that we need more implementation projects in this country? There. I mentioned it.
And of course Montreal was a site for the Ipergay study, which was the other big PrEP news out of CROI this year… read all about it in my next article!