On October 16 the PROUD Study Team announced that all participants enrolled in this pilot trial of daily Pre-Exposure Prophylaxis (PrEP) in the UK will be offered immediate PrEP. This was a challenging decision for the ANRS-led IPERGAY study which is investigating the efficacy of the same antiviral (Truvada) for the prevention of HIV acquisition, though in a different, intermittent regimen.
Following this decision, the IPERGAY Data and Safety Monitoring Committee (DSMB, an independent body that has access to all trial data) met to review the study results so far and today recommended that all participants in IPERGAY should be offered PrEP “on demand”, chiefly closing the controversial placebo arm of the study.
As with the PROUD announcement this is a relief and IPERGAY will join the rank of the six studies already showing that PrEP works when taken for the prevention of HIV acquisition. The efficacy of Truvada in IPERGAY has not been revealed but the DSMB found “a significant difference in incidence between the two groups [drug on demand and placebo] with a very significant reduction in the risk of HIV infection” in the treatment arm, “much higher than the one observed in the iPrEX trial”, which showed a 42% reduction of the risk of HIV infection with a daily PrEP regimen.
The French newspaper Le Parisien – quoting Jean Michel Molina IPERGAY’s study Chief Investigator, reports an efficacy of PrEP”in the order of 80%“. That figure will have to be refined and without a p-value and confidence interval, should be handled with care.
The announcement came out as many researchers, clinicians, and activists are attending the HIV Research for Prevention conference in Cape Town. There is an indubitable air of delight amongst the conference attendees, but also there are already a number of questions being raised about what was really being measured in the study and how stopping it early will affect PrEP availability and future use.
Data presented by the PROUD Study Team at the HIVR4P conference yesterday showed that participants enrolled in this trial were very much sexually active, reporting 10 partners during the last 90 days prior enrolment, 7 of which were new partners.
if your “sex-planning” looks like this, daily PrEP if probably better for you than intermittent PrEP.
Number of partners and frequency of sex acts will be critical when assessing the real efficacy of any intermittent PrEP regimen. IPERGAY complex regimen of pill taking centred on the time of sex, may well end up looking more like a daily regimen than an intermittent one for the very sexually active, providing little information about the efficacy of intermittent regimen for those with low sexual activity.
Participants in IPERGAY take 2 pills from 2 to 24 hours before anticipated sex. If they then actually have sex, they take 1 more pill 24 hours after sex and another a further 24 hours after that, which means that Truvada can be taken at least 3 consecutive days out of 7 in a week. Two sex acts equally spaced in the week would mean a 6-day coverage, add a few missed encounters, and this intermittent regimen becomes a daily one, especially in a study that has already reported a good adherence.
Source : http://www.hivnet.ubc.ca
Frequent users will be exposed more often to Truvada and have higher concentration of drugs in their body than those who engage only occasionally in sex (iPrEX has already showed that taking pills 4 times a week was effective to reduce the risk of infection).
In July 2014, Prof. Molina presented preliminary adherence data at the IAS conference in Melbourne. There he showed that 50% of the participants (little less than 130 at the time) where taken 15.4 pills a month (ranging from 8 to 23). This data clearly points to a “weekly” regimen rather than an intermittent, peri-coital regimen. Overall, 3% of the participant were taking PrEP daily. In itself this is not a problem, as currently PrEP is and should remain mostly targeted to those who frequently engage in unprotected sex.
There is still a lot we do not know about the pharmacokinetics of Truvada for HIV prevention in the real world and therefore there is an urgent need for a number of (creative!) studies investigating how long and how much drugs need to be taken to be effective in preventing HIV acquisition and how long efficacy persists when user stop taking them. However, this should in no-way delay the implementation of PrEP in a carefully supervised environment.
Today, IPERGAY adds one more piece of evidence supporting rolling out PrEP in particular in high risk populations and the recommendations of both the PROUD and IPERGAY DSMB are a strong message for the health commissioners to speed up the process of making Truvada available in more than one country.
~rjtSee also the Aidsmap Report by Gus Cairns “Second European PrEP study is closed early due to high effectiveness” and also from Gus Cairns D-day for the Pill for HIV. Understanding the PrEP regimen in IPERGAY. In french but quite straightforward.