Ipergay is a double-blind placebo-controlled clinical trial measuring the efficacy of oral PrEP “on demand”. There were over 350 participants in France and 53 participants in Montreal. All participants received a standard prevention package that included STI testing and treatment, vaccination against Hepatitis A and B, condoms and lube, risk reduction counselling, and post-exposure prophylaxis (PEP). Participants were randomised to receive either Truvada or placebo pills. The use of placebo in this trial was not without considerable controversy, but that is another story…
The “on demand” regimen consisted of asking participants to take two pills before sex and two pills after sex. The first two pills were to be taken between 2-24 hours before sex. The third pill was to be taken the next day (up to 24 hours after sex), and the fourth pill was to be taken on the subsequent day (48 hours after sex). For example, if you were going to have sex on Saturday night, you would take two pills earlier that day, one pill on Sunday, and one last pill on Monday. If you have sex on any day when you were already taking one pill, you tag on another pill at the end (48 hours later). You don’t take another double-dose. So if you have sex once a week, you’d end up taking 4 pills. If you have sex twice a week, say on Saturday and Wednesday, you’d essentially be on a pill-a-day all the time.
When the PROUD study announced in October 2014 that it was offering all participants Truvada because its effectiveness was so high, Ipergay looked at its data as well. Later the same month, it also announced that it had found very significant effectiveness, and that it was offering all participants Truvada.
Findings in a nutshell
Participants who received Truvada were 86% less likely to become HIV-positive than participants who received the placebo pills. This is based on the fact that there were 16 infections among trial participants: 2 in the Truvada arm (equivalent to 0.94 infections per 100 person-years), and 14 in the placebo arm (equivalent to 6.6 infections per 100 person-years).
Both participants in the Truvada arm who seroconverted had stopped using PrEP several weeks before they seroconverted. 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. 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 a very significant reduction in HIV risk. And what an incredible coincidence that both PROUD and Ipergay showed the exact same reduction in risk. It is also impressive to see that participants were able to follow what seems at first to be a rather complicated dosing regimen.
Like PROUD, Ipergay showed effectiveness in a surprisingly short period of time, with only a relatively small number of participants. Like PROUD, this is probably due to a combination of three factors: 1) Truvada works really well when taken consistently; 2) participants had fairly high adherence rates, (despite the 50% chance of receiving a placebo in the case of Ipergay), and 3) participants were at very high risk. Once again, the arm that did not receive Truvada had a very high incidence rate—in this case 6.6 per 100 person-years. The participants were on average 34-35 years old. By my calculation, if we follow 100 of these participants without offering PrEP, 29 of them will be HIV-positive by the time they are 40 years old. And again, this is despite providing participants with condoms and lube, STI testing and treatment, risk reduction counselling, and PEP. And once again, this is among a cohort of predominantly white, educated, employed gay men in their mid-30s on average. By contrast, if we followed the same group but added PrEP to their prevention package, among those same 100 HIV-negative men who are 34-35 years old, only 5 of them would be HIV-positive by the time they are 40 years old.
So like PROUD, Ipergay 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. They are also able to follow what some would say is a relatively complex “on demand” regimen.
The questions that I asked about PROUD apply to Ipergay: 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? It is probably safe to say that more research is needed in this population.
Participants seem to have taken on average 3-4 pills a week. That’s about half of what would be taken with the currently recommended regimen of one pill per day. If the efficacy of Ipergay’s “on demand” regimen can be confirmed, that would significantly reduce the cost of the intervention, and reduce even further the already low level of risk for side effects and toxicity associated with a daily pill. The US CDC has already issued a statement saying it still recommends daily dosing, for a number of reasons. It would seem that further research is needed before PrEP guidance changes.
Upon the release of the PROUD and Ipergay study results, the European AIDS Treatment Group (EATG) and AIDES in France, backed by over 80 European HIV and LGBT groups, immediately issued what they call an urgent HIV Prevention Manifesto demanding that PrEP be made available.
The Warning has already issued a statement calling for the Quebec interim notice on PrEP to be revised, for PrEP guidance to be developed, and for community-based organizations to promote PrEP as a prevention strategy, and to facilitate referrals for gay men interested in PrEP.
I’ve previously commented on the interim notice from Quebec—which to this day remains the only PrEP guidance in Canada, despite its . shortcomings. A complete set of guidance is desperately needed in this country.