Hello Dr Sherer, is PEP failure only because of adherence issues, or might also be because the virus strain acquired is resistent to the PEP drugs? Or worse, could adherence problems during PEP cause the virus to become resistant to the PEP drugs?

Thanks for taking time to look at my question,


While we have evidence that PEP (which stands for post exposure prophylaxis) works, we do see PEP failures on occassion, and it is not always clear why there has been failure. There are many aspects of PEP that are poorly understood.

Things that may contribute to PEP failure include adherence to the drugs and resistance to the drugs, as you suggest. Current PEP recommendations do address the possibility of drug resistance in the selection of the best PEP regimen in a given circumstance.

There are other possible causes of PEP failures, such as the amount of time from exposure to the start of PEP and the size of the inoculum.

We know from our experience with health workers that adherence to PEP regimens is often incomplete, with up to 50% of exposed individuals failing to complete the regimen in some studies. As you suggest, this may compromise the effectiveness of the PEP regimen, and may allow for the development of drug resistance.

Health professionals engaged in PEP can do their best to reduce PEP failures by starting the ART promptly, ideally within 4 hours of the exposure, and by choosing the ART regimen carefully after a full assessment of the source patient (and their treatment history and prior resistance tests, if available). The exposed individual can make their contribution by taking all of the recommended doses of ART during PEP.