Second European PrEP study closes placebo arm early due to high effectiveness

All participants receiving placebo in IPERGAY trial to be offered PrEP

In an extraordinary development, a second European scientific trial of pre-exposure prophylaxis (PrEP) has had its randomised phase closed early due to high effectiveness, just two weeks after the UK PROUD trial did exactly the same thing.

The investigators of the IPERGAY trial, which has six sites in France and one in Canada, announced today a “Significant breakthrough in the fight against HIV and AIDS” because IPERGAY had successfully demonstrated the effectiveness of its PrEP regimen.

IPERGAY’s early closure is significant not only because it adds confirmation that PrEP can be highly effective, but because it was testing an innovative, intermittent (“on-demand”) PrEP regimen. In this study, participants did not take PrEP daily, but only when they anticipated having sex. The regimen involved taking two pills of Truvada (tenofovir + emtricitabine) in the 24-hour period before anticipated sex and then, if sex happened, two separate one-pill doses in the two days following sex.* This extends the versatility of PrEP and provides an alternative regimen to daily dosing.

Glossary

data safety monitoring board (DSMB)

An independent committee of clinical research experts that reviews data not available to the study team while a clinical trial is in progress to ensure that participants are not exposed to undue risks. A DSMB can recommend that the study be stopped if the intervention is not effective, is causing harm to participants or the study is not likely to serve its scientific purpose. Also known as an Independent Data Monitoring Committee (IDMC).

on demand

In relation to pre-exposure prophylaxis (PrEP), on-demand dosing is an alternative term for event-based dosing. See ‘event based’.

protocol

A detailed research plan that describes the aims and objectives of a clinical trial and how it will be conducted.

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

opportunistic infection (OI)

An infection that occurs more frequently or is more severe in people with weakened immune systems, such as people with low CD4 counts, than in people with healthy immune systems. Opportunistic infections common in people with advanced HIV disease include Pneumocystis jiroveci pneumonia; Kaposi sarcoma; cryptosporidiosis; histoplasmosis; other parasitic, viral, and fungal infections; and some types of cancer. 

IPERGAY was run by the French national AIDS research institute, ANRS, and began in February 2012. It randomised gay men at high risk of HIV infection to the Truvada regimen or to a placebo – a protocol that caused some controversy among activists who felt studies such as iPrEx had already demonstrated that PrEP worked. All participants were also offered a package of measures including “personalised and frequent” counselling, repeated HIV testing, screening and treatment for other sexually transmitted infections, hepatitis B vaccination, condoms and lubricant. At the time of closure of its randomised phase, the trial had approximately 400 participants.

Following the decision taken by the PROUD study investigators to give daily Truvada to all its participants, ANRS urgently contacted the IPERGAY trial data safety monitoring board (DSMB) for a review. The DSMB examined the unblinded data and found a significant difference in incidence between the two groups with a “very significant reduction” in the risk of HIV infection in the PrEP group, which a press release describes as “much higher than the one observed in the IPREX trial” (as is the case with PROUD). The DSMB therefore recommended that all trial participants were offered Truvada, taking it “on demand” as in the trial.

As with PROUD, no actual effectiveness figure or other quantitative data were released, pending full analysis of the figures. The full results should be available early in 2015.

The trial will continue in non-randomised form for at least a year, as will PROUD, because of the need to demonstrate that “on demand” PrEP can have long-term benefit and to gather data on safety.

Principal investigator Professor Jean-Michel Molina said, "The biomedical concept of on-demand PrEP at the time of sexual exposure, in a broader prevention framework, is validated. We owe this to all trial volunteers without whom we could never have achieved these results". He adds that “condoms remain the cornerstone of HIV prevention. Combining all prevention tools that have proved to be effective will certainly allow us to better control the HIV epidemic.”

Professor Jean-François Delfraissy, Director of ANRS, commented, "This is a major breakthrough in the fight against HIV. The results of the ANRS IPERGAY trial should change national and international recommendations for HIV prevention".

*Note: this article has been updated to clarify the exact dosing schedule used in the IPERGAY study.

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