Why does on-demand PrEP (2:1:1) have a 2 to 24 hour window for the first dose?
I would like to know with PrEP on demand, why the advice is for the initial double dose to be take anything from 2 to 24 hours before having sex.
Why is there such a wide time frame?
Are there significant advantages to taking it more than two hours before? i.e. is there an increasing benefit with increased time?
Cant find an answer to this.
Thanks – great questions – and there are a couple of related reasons.
The main answer is that studies in animals supported that anywhere in this window might be effective. So this was the information used in the IPERGAY study that proved 2:1:1 dosing works. Because only IPERGAY has studied 2:1:1 dosing, the recommendations need to follow this study.
The potential benefits from taking if closer to 24 hours before is that this would let good concentrations of both the drugs in PrEP be at good levels. Although emtricitabine is absorbed within about 30 minutes, tenofovir can take a much longer time, maybe 24 hours to get to good levels in rectal tissue.
But this is just speculation – because no good study has produced this level of detail. Also, because IPERGAY was so effective that no-one who followed this dosing advice became HIV positive.
Even if you are going to be late with the first dose, advice is still to take is as soon as you can.
Lots of details about PrEP are not really known. This includes the exact drug levels needed for protection. Also, the time HIV takes to establish infection.
But even without knowing these things, when PrEP is really effective at preventing HIV.
This recently updated UK guide has more info: