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CROI 2015: On-Demand PrEP Prevents 86% of HIV Infections in Ipergay

A French and Canadian study of pre-exposure prophylaxis (PrEP) presented today at the 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle found that the HIV infection rate for participants taking an intermittent PrEP regimen was 86% lower than for people taking an inactive placebo. Extraordinarily, this is exactly the same level of effectiveness that was demonstrated in the English PROUD study, whose outcomes were presented 15 minutes before Ipergay. Ipergay is a very different study than PROUD and it is encouraging that 2 different ways of taking PrEP have both proved effective in gay men, at least in a western European context.

[Produced in collaboration with Aidsmap]

About Ipergay 

All trials of oral PrEP so far (other than small safety trials of experimental drugs) have involved taking either Truvada (tenofovir/emtricitabine) or tenofovir alone once a day. The French researchers wanted to see if taking PrEP only around the time participants were actually exposed to HIV would work too. The primary reasons for doing this would be to see if adherence was better, and also to save money, as PrEP's per-unit cost is far higher than other prevention methods such as condoms. Intermittent dosing could also lower the risk of side effects. Animal studies had shown that intermittent PrEP might work. 

In Ipergay, gay men and other men and transgender women who have sex with men, and were at high risk of HIV infection, were asked to take 2 Truvada pills or a placebo from 1 day to 2 hours before they anticipated having sex. If they actually did have sex, then they were to take another pill 24 hours after having sex and a fourth pill 48 hours after. The period of taking PrEP would thus cover 2 to 3 days. If they continued having sex, they were told to continue taking PrEP until 48 hours after their last experience. 

As in PROUD, all participants also received risk-reduction counseling, were provided with condoms, had tests every 3 months for HIV and other sexually transmitted infections (STIs), and received hepatitis A and B vaccines if needed.

Ipergay started enrolling participants in February 2012. Like PROUD, it was intended to be a pilot study demonstrating the feasibility of its approach and the investigators initially planned to recruit 350 participants.

By November 2014 the study had in fact recruited exactly 400 participants who were given Truvada or placebo. Altogether 445 actually came forward but 14 (3.1%) were found to have acute HIV infection when they were screened or on randomization and various others. Thus 400 people are included in this analysis, though in fact by de-randomization in November, 47 participants had withdrawn or disappeared, so the number in the study at this point was 353. 

The average age of participants was 35 years, 95% were of white ethnicity, 90% had competed secondary education, only 21% had a primary relationship, and 20% were circumcised. 46% had used methamphetamine, amphetamine, GHB/GBL, cocaine, or ecstasy in the last year. At baseline 26% had been diagnosed with gonorrhea, chlamydia, or syphilis in the last year. 

The average number of sexual partners participants had had in the previous 2 months was 8. 70% had had condomless anal sex in the previous 2 months. A proportion -- 28% in the Truvada arm and 37% in the placebo arm -- had used post-exposure prophylaxis (PEP) before. 

Effectiveness and Adherence 

In November 2014, prompted in part by the PROUD study researchers’ announcement that all participants were to be offered PrEP at once because of high effectiveness, Ipergay’s Data and Safety Monitoring Board also looked at the HIV incidence data and found high effectiveness too. They announced that Ipergay would be de-randomized and all participants offered Truvada just 2 weeks after the PROUD announcement. Like PROUD, Ipergay continues as an unrandomized implementation study. 

As with PROUD, HIV incidence in Ipergay was higher than anticipated, and this meant that the study could prove effectiveness in what is for a prevention study a remarkably small number of participants, and in a short space of time. The longest anyone was in the trial before the November de-randomization was 20 months but the median time was only 9 months. 

During this time 2 patients allocated to Truvada became HIV positive and 14 allocated to placebo did so (compared to PROUD, where there were 3 and 19 infections seen in the immediate and deferred arms). HIV incidence -- the annual rate of HIV infection seen per 100 participants -- was 0.94% in participants taking Truvada and 6.75% in patients on placebo (compared with 1.3% and 8.9%, respectively in PROUD). 

This translated to an effectiveness of 86% -- exactly the same rate as seen in the PROUD study, with 95% confidence intervals of 39.4%-98.5%. These are not directly comparable with PROUD, which used 90% confidence intervals. 

The 2 participants in the Truvada arm who acquired HIV did not become infected until late in the study -- one 16 and one 21 months after entering the study. Principal investigator Jean-Michel Molina said that the 2 participants had pretty certainly stopped taking PrEP by that time -- they had even been returning full unused pill bottles to the clinic. As with PROUD, there was certainly no evidence that anyone who had been taking Truvada had become infected. 

Data were presented at the International AIDS Conference last year indicating that adherence in Ipergay had been high -- as it must have been to achieve the effectiveness seen. This was achieved on an overall pill usage of 14 pills per month, or approximately half the number that would be used if participants had taken them daily, with good adherence. 20% of participants took over 25 pills a month, i.e. the equivalent of almost daily, and 20% less than 4 per month, i.e. less than 1 a week. 

Participants were also asked if they had taken PrEP the last time they had sex. 43% reported that they had taken it according to the protocol, 29% had taken some doses, and 28% had not taken any. As Molina said, this did not mean they had necessarily been at risk, as participants might vary their PrEP-taking according to whether they perceived themselves as being at risk. 

Behavior Change, STIs, and Side Effects 

There was no evidence of behavior change in the study. The proportion of participants reporting at least 1 episode of condomless anal sex in the previous 2 months remained at 70%, as did episodes where the participant was the receptive partner. The number of partners remained at just under 8 in the last 2 months, and the number of sexual acts remained completely unchanged at 10 in the last month. 

During the study 35% of participants were diagnosed with a sexually transmitted infection including 20% with gonorrhea and 10% with syphilis. Molina reported 2 in a 100 participants acquired hepatitis C virus, equating to 8 infections. 

There was a higher rate of gastrointestinal side effects such as nausea, diarrhea, or abdominal pain reported by participants taking Truvada than those on placebo (13% versus 6%). There were 2 patients (1%) with transient decreases in their kidney function as measured by their creatinine levels, but only 1 person in the entire study discontinued Truvada due to an adverse event -- a suspected drug-drug reaction. 

Summarizing the study, Molina commented that Ipergay showed that gay men were capable of taking PrEP in a way that suited their lifestyle and maximized their safety, if offered the chance to do so.

SEE ALSO:

PrEP Stops 86% of HIV Infections in PROUD Study

PrEP Provides 86% Protection in 2 Studies [VIDEO]

2/24/15

Reference

JM Molina, CCapitant, B Spire, et al for ANRS Ipergay Study Group. Pragmatic Open-Label Randomised Trial of Preexposure Prophylaxis: The PROUD Study. 2015 Conference on Retroviruses and Opportunistic Infections. Seattle, February 23-24, 2015. Abstract 23LB.

Other Source

CDC. CDC Statement on Ipergay Trial of Pre-exposure Prophylaxis (PrEP) for HIV Prevention among Men Who Have Sex with Men. Press release. February 24, 2015.