The Ipergay study results of pre-exposure prophylaxis (PrEP) Intermittent were published in the New England Journal of Medicine (NEJM) on 1 December, World Day to combat AIDS. The official journal published the results and has changed little since those presented by the CROI in February 2015by principal investigator Jean-Michel Molina, but the researchers make a number of additional observations and are especially cautious about non-interpretation of a study that had only 400 participants - very small for a prevention study - and an average of nine months follow-up .
Nevertheless, Ipergay represents a major innovation in Prep. He is the first, and so far only, randomized study to show that an intermittent schedule of PrEP, only when anticipated to sex, can be as effective as daily taking PrEP.
To summarize the results: in Ipergay, 400 gay men and transgender women were randomly assigned to takeTruvada(tenofovir / emtricitabine) or a placebo.
In the scheme participants were asked to take a double dose (two tablets) 24 to two hours before sex prediction and then a pill of both the two days after sex. If they continued to have sex, they were told to keep taking one pill a day until two days after the last sex. If they reiniciassem sex, they had to take a double dose last if more than one week from the sex.
The use of placebo was considered somewhat controversial in some activists and Ipergay considered that the efficacy of PrEP has been sufficiently demonstrated by the study iPrEx of 2010. However, effectiveness in iPrEx was only 42% of the total, and the researchers comment that "the use of placebo was considered justified because of the inconsistent effectiveness of PrEP in previous tests and moderate efficacy iPrEx second proof."
There was 19 HIV infections throughout the Ipergay trial period, but three of them were determined to have happened shortly before participants started PrEP / placebo. 14 infections were identified in men who were randomized to receive placebo and two men affected in use of PrEP.
In fact, none of these men had taken PrEP, or no PrEP in the two months before they positive test them (in Ipergay, outpatient consultations were held in all eight weeks). A new detail added in NEJM cohort is that participants were asked to return any unused as well visit the they were diagnosed, these two participants returned 60 and 58 60 respectively of tablets given to them two months earlier.
The 14 / 2 differences in infections represent a 86% (95% confidence interval: 40% -98%) reduction in the risk of HIV infection in study participants assigned toTruvada. HIV incidence in the study was 6,6% per year in the placebo group and 0,91% in the group receiving Truvada. The 6,6% is more than double the expected incidence of 3% for prior to the study, although not as high as the 9% observed in different PrEP arm in the PROUD study.
Study participants and sexual behavior
We learn a little more about the participants in the study report. The average age was 34,5, with one in seven participants aged 18 24 years and the other seven 25 the 29. Most (62%) aged 30 49 the years. Only a quarter said they were in a most remarkable relationship - and this is probably one of the reasons for volunteering for the study - 30% of people in a relationship, their partner was HIV-positive (a little more than armTruvada).
Half of the participants were from Paris and 11% of Montréal in Canada, with others in Lyon, Nice, Nantes and Tourcoing, France. They had high levels of recreational drug use (44,5% last year, had used ecstasy, methamphetamine, amphetamine, cocaine, GHB or GBL) and 25% had more than five alcoholic drinks a day last month.
The men had a median of eight sexual partners in the last two months - similar to PROUD where participants an average of ten in the previous three months. This was the only behavioral indicator that has changed slightly during the study: he fell 7,5 partners for two months in the placebo arm and not in the Truvada arm, which was statistically significant, but still likely to be found.
Apart from this slight drop in the number of partners in the participants in the placebo group, sexual behavior has not changed during the study, with 70% throughout the study and in both arms having insertive unprotected anal intercourse in the previous two months, and two thirds of those who received unprotected receptive anal sex.
Adherence was as described above: while it is difficult to measure or even define 'membership' to an intermittent scheme, 86% of participantsTruvadaThey had tenofovir levels in the body consistent with what they would have took at least one dose per week. Interestingly, they did so eight men on placebo; these three had taken post-exposure prophylaxis (PEP), but probably the other five had taken "informal PrEP."
Only 43% self report, however, said they had taken PrEP in accordance with the study scheme the last time you had sex, while 28% had not taken at all.
On average, half of the participants were PrEP time, ie 15 days per month; 17% took PrEP over 26 days per month, or basically daily while 31% took for eleven days or less, or less than 2,5 days per week, a level which, according to the study data iPrEx would not be enough to protect them against HIV if it was a stable level of PrEP.
There was, however, a huge variability for each participant, "the bondline during the study, while some advantage on continuously and the other in practically all, many of the participants have stopped or restarted PrEP irregularly, many with gaps several months without Prep. Once irregular adherence (and the fact that 29% of sex was not covered by PrEP in all) was not associated with HIV infection, it probably means that the participants were able to correctly assess their risk levels and only if used PrEP when they judged the ratio as high risk.
Fourteen percent of participants had PEP during Ipergay (16% ofTruvadaand 12% in the placebo group), compared with an average of 18% of proud.
There were no serious adverse events related to study medication although a participant had to stopTruvadadue to suspicion of a reaction with dabigatran anticoagulant. However, they were not significantly greater than the events of the gastrointestinal tract such as nausea, vomiting, abdominal pain or diarrhea, the group made use of more Truvadathan the placebo group (14% versus 5%).
Creatinine levels, an indication of kidney performance, were raised in 18% of participantsTruvada10% versus the placebo group. Two participantsTruvadaThey had decreases in creatinine clearance less than 60 ml / min, the definiticção of mild renal dysfunction, but these were transient and not definitive.
The observations and conclusions
In their observations, the researchers Ipergay are especially cautious about their findings. They note that although the effectiveness of PrEP Ipergay was almost the most up to date, "short follow up time for our study may have increased the likelihood of an over-estimation of effectiveness due to high initial adhesion."
They add that "given that the participants had an average of 15 tablets per month, the results ... can not be extrapolated to [homosexuals] that have less frequent sex and therefore would be taking tenofovir / emtricitabine in a scheme yet more intermittent. "
By definition, men who have sex less often have lower incidences of HIV and therefore a much larger study would be needed to determine whether intermittent PrEP was effective for them.
Molina JM et al.On-demand preexposure prophylaxis in men at high risk for HIV-1.NEJM early online publication, DOI: 10.1056 / NEJMoa1506273. To 2015.See full text here