Also what is considered a high risk exposure? By high risk I mean an exposure where we should go see a doctor about testing or medication. Are all sexual intercourse encounters with an unknown status partner considered high risk even if a condom was properly used? I saw that some answers by Dr. Hook and Dr. Handsfield were differing in answers with regards to insertive intercouse being 1/1200 (Hook) and 1/2500 (Handsfield). What is a good critiria to follow with regards to judging when a specific instance requires immediate medical attention?  

You are exactly right about the problems in studying PEP and understanding its true efficacy. Only a few primates have been studied, with uncertainty about how reliably the data can be extended to exposed persons. The animals are inoculated in ways that virtually guarantee infection, almost never the case in humans; and even these risks are calculated on the basis of fallible human memory. All we have go on are biological principles, the limited data in primates, and providers' observations of their own patients -- making it easy to understand widely varied estimates on actual effectiveness between various websites or from different doctors or clinics. Having said all that, most experts would agree that efficacy is maximal, perhaps near 100% when started within 12 hours, but I could not make a strong case against estimates of 80% or 90%.

To answer your opening question, I doubt that missing a dose or two of PEP would reduce efficacy and certainly a two hour delay in dosing would make no difference.

There is no single definition of a high risk sexual exposure; it's very much in the eye of the beholder. Some people are freaked out by learning there was one chance in a million they were infected; others are blasé about much higher risk levels. The published data (summarized in 2015 by CDC https://www.cdc.gov/hiv/pdf/risk/estimates/cdc-hiv-risk-behaviors.pdf) are based entirely on reports of infected persons on how and when they believe they acquired HIV, which sexual events they remember, the likelihood the suspected source partner actually has HIV, and so on. Is 4 in 10,000 for insertive vaginal sex (1 in 2,500) "high risk"? An earlier CDC report (2005) estimated 1 in 1,000 for the same exposure. In advising the typical forum user, does it matter? If there's a 1% chance the female partner has HIV, and if a condom was used (and assumed to be 99% effective), the odds the exposed person acquired HIV becomes one chance in 25 million (Handsfield) or one in 10 million (Hook). Both estimates obviously are zero for all practical purposes, so who cares?

Most potentially exposed persons do not go through such a calculation after an exposure they regret or that frightens them, nor would I expect them to. Probably most PEP providers don't do so either -- although I believe they could and should much more often. Fortunately, PEP is extremely safe, allowing for a low threshold for a decision to prescribe it. Our forum experience is that some providers often prescribe PEP on patient request, with little regard for actual risk. We often point to a downside that both exposed persons and their doctors usually don't think about:  if PEP fails, it prolongs the window period to confirmatory testing; the clock starts with the last dose of PEP, not the exposure, and some experts believe that following PEP the window for an AgAb (4th generation) HIV blood test is 3 months. Therefore an anxious or frightened person is looking at 3-5 months of uncertainty rather than having a conclusive answer 6 weeks after exposure (and nearly conclusive at 4 weeks). That's a lot of sleepless nights for some people and often a strong argument for limiting PEP to those with much higher risk.

I hope this somewhat rambling reply is helpful to you. Let me know if anything isn't clear.

HHH, MD

Probably most people in whom PEP fails to prevent HIV have positive RNA tests and AgAb tests by 17 days. However, it isn't certain:  there are no solid data, and therefore -- as stated above -- almost all experts recommend testing with an AgAb 6 weeks after completing PEP, and some say 3 months. Yes, having PCR does help with "this dilemma" as you put it. Still, in absence of solid data, most experts would not rely exclusively on the PCR result.

"Secondly, assuming a condom was used properly....?" Yes, this certainly should influence the decision for PEP; and yes, every instance is a case-by-case situation that should consider the overall risk for the particular exposure, and not attempt to apply any sort of general rule. This is why no authoritative agency has published or promoted specific PEP guidelines:  it's always case by case. Had you come to my clinic in this situation, we would not have recommended PEP. In fact, we would have refused to prescribe it. We would have recommended against PEP even if no condom was used. 

But now that you have gone that route, you should have a final AgAb test at least 6 weeks after your last dose of PEP.

Problem is I am already on PEP again for another exposure so if I were to take the 4th gen test 6 weeks post last pill for the earlier exposure would the results still be valid (for the earlier exposure at least) since I’m on PEP ? 

And according to your advice I’m assuming you mean to say that you viewed my earlier exposure as not even a high risk exposure therefore not requiring the prescription of Pep? Your calculations were very insightful and I guess does illustrate how ludicrous the fear of HIV can be from singular exposures but I think it’s also because the cost is so high since the virus stays with your forever so people naturally have a heightened fear despite the astronomically unlikely odds. That being said I also feel uneasy until I can have a conclusive result from my cases. 

Don't get tested again until 6 weeks after completing your most recent PEP; there is no point in ever testing for HIV while taking anti HIV drugs.

That completes the two follow-up exchange included with each initial question and so ends this thread. I hope the discussion has been useful. Stay safe.