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On-demand Prep?

Aug 15, 2017

Hi Damon,

I was wondering why the "French" on-demand Prep is still not recommended in the US?

Response from Mr. Jacobs

Hi there,

Thank you for a great question! Although I can't speak for the U.S. Center For Disease Control (CDC), I can speak to their hesitations to endorse the French "on-demand" PrEP protocol, and the shortcomings in their logic.

So let's start with reviewing PrEP itself - a drug called "Truvada" that has been shown to reduce risk of acquiring HIV by more than 99%. In July 2012, the U.S. FDA became the first health organization to approve the use of PrEP, recommending for it to be used daily by any individual at risk of acquiring HIV. Both the CDC, and the international World Health Organization (WHO) followed suit in 2014 by providing guidelines for medical providers, which continued to endorse daily dosing for maximal benefit.

In early 2015, the French "Ipergay" results were released which demonstrated that people did not necessarily have to take Truvada daily in order to be protected from HIV, especially if they were not regularly sexually active. People in the study were instructed to take two doses of Truvada together 2-24 hours before a sexual event, then another dose 24 hours later, and another dose 24 hours after that. If someone remained sexually active they were instructed to just keep using Truvada daily. In this trial, no one who took PrEP following this regimen acquired HIV. Only the people who did not take the medications became HIV positive. (

So far, so good. However -- there was one caveat to this research: The 400 participants in Ipergay were a fairly active bunch. So much so that most of them ended up taking an average of 4 or more pills per week, which we already knew provided sufficient coverage from HIV ( Only 20% of the participants in Ipergay took the drug less than 4 times per week.

When the U.S. CDC saw this data, they found it informative, but incomplete. Again, because the participants were using Truvada so frequently, the CDC did not believe this convincingly told us if Truvada worked well on demand. Or to put it in the words of Jonathan Mermin, Director, CDC National Center for HIV/AIDS:

"Since available data suggest that men in this study were taking PrEP an average of three to four days per week, CDC cautions that researchers do not yet know if this regimen will work among MSM who have sex less frequently and would therefore be taking PrEP less often. It is not known whether the regimen will work if taken only a few hours or days before sex, without any buildup of the drug from prior use. Studies suggest that it may take days, depending on the type of sexual exposure, for the active drug in PrEP to build up to an optimal level for preventing HIV infection." (

So that was why the "on-demand" dosing regimen was not endorsed in the United States. However -- newer research just released in July, 2017, studied a subset of Ipergay participants who took took Truvada less than 15 times per month. Even in that group, that were still no new HIV acquisitions. As Ipergay principal investigator Jean-Michel Molina commented: "Now that more than 3000 people are taking PrEP through the public health system in France, with over half of them taking it on demand, we expect to see more evidence of its effectiveness." (

Will this new evidence inspire the U.S. CDC to change their tune? My guess is no. The CDC isn't keen on updating their protocols very readily, even when there is compelling data to do so (they are still woefully behind on sharing up-to-date science related to PrEP and Treatment As Prevention's efficacy on their websites).

Even though the U.S. CDC doesn't recommend it, I do know people in the U.S. who have adopted this strategy. It seems to work well if one can accurately predict the time/place of all their sexual encounters. But for people like me, who can't always predict when that big moment is going to rise, daily dosing still seems to be the preferred and more efficacious way to prevent HIV.

Could I have contracted HIV from my partner?
Female To Female HIV via threesome?

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