[Question #7924] PEP Effectiveness

50 months ago

I would appreciate hearing your comments on PEP effectiveness when the first dose is initiated 4½ to 5 hours post exposure from a single instance of unprotected receptive anal intercourse (broken condom) from a male insertive partner of unknown HIV status.

I have seen literature which indicates that PEP's effectiveness is "excellent" when administered within 24-hours post exposure & that PEP should not be administered after more than 72-hours post-exposure. While I understand that the efficacy of PEP is difficult to ascertain in the absence of clinical trials, given your experience & the use of occupational PEP for several decades, is there any updated estimation of the effectiveness of PEP when administered soon (4 to 5 hour) post exposure? Are you able to provide a definition of what PEP's "excellent" efficacy/effectiveness means in this context? Thank you.

Edward W. Hook M.D.

50 months ago

Welcome to our forum and thanks for your questions. They are excellent questions. I wish I had equally excellent answers but, For better or worse, postexposure prophylaxis (PEP) is so effective that to study this appropriately would take thousands and thousands of study participants. What we do know however is that PEP is highly effective at prevention of HIV. Whether that means that risk is reduced 80% or 90% is not possible to say. Taken in context however, when you realize that less than 1% of exposures without use of PEP result infection, irrespective of the sort of exposure you’re talking about, a 80 to 90% reduction in risk is important and makes a huge difference.

From a theoretical and pharmacologic perspective, the sooner PEP is started after a potentially infectious encounter, the better. When HIV infections are acquired, the events leading to hinfection occur quickly, certwithin 72:hours of exposure. Hence the sooner PEP is started, the better.

Regarding my opinions about PEP it’s effectiveness, I believe in its efficacy however for persons at no risk for HIV, PrEP including PrEP on demand is a far better approach to staying safe.

I hope this information is helpful to you. If they are further questions, please don’t hesitate to use you were up to two follow-up questions for clarification. EWH

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50 months ago

Thanks for your swift response. I believe you have quite thoroughly answered my question.

If I may just follow-up then, much of the literature (CDC, NIH, state & foreign health authorities) cite specific reasons for PEP failure (ie. risk behavior post-PEP, methamphetamine use, failure to adhere to PEP protocol for 28-days and/or PEP started >72-hours post-exposure). At the same time, several articles (ie. aidsmap.com, catie,.ca, etc) citing "expert" opinions seem to indicate that with an early PEP start post-exposure (ideally <24-hours); consistent adherence to a 28-day course of PEP; & no additional risky exposures, that PEP is "nearly" or "almost 100% effective". Clearly, the statistical difference between 80, 90 & "nearly 100%" effective is minuscule at best, would you agree with that general observations & from your experience, have there been any studies which have shown a different profile/reasoning for PEP failure when administered <24 hours post-exposure?

Again -- I don't want to beat a dead horse & accept that the cited "80-90%" effective is not materially statistically different than "nearly" or "almost" 100% effective but would appreciate any thoughts you may want to add in that regard.

Thank you.

Edward W. Hook M.D.

50 months ago

As mentionrd,above, there are no high quality studies that provide the sort of precision regarding PEP effect that you seek. As the result of numerous scientific studies and because less than 1% of exposures to HIV infected, untreated partners lead to infection and because many exposures, even in carefully designed studies, are to persons without HIV, the size of the numbers of persons that would need to be studied and the duration such a study would need to be carried out is impractical, Hence the failures are simply not numerous enough to provide a statistically more precise figure. Based on case series and individual observations, we know that PEP works, that PEP failures increase as the interval between exposure and starting PEP increases, and believe that PrEP is more effective than PEP. My advice is that if a person knothey are or will be at risk, PrEP is preferable and PEP is best suited for persons who are unexpectedly exposed. EWH ---

50 months ago

Thanks, Dr Hook.

After reading your responses, I undertook a further search including answers on this forum & belatedly came across 2 responses from Dr Handsfield to questions where he quantified PEP effectiveness at "nearly 100%" when PEP was started within 5 hours & 36 hours (respectively) after potential exposure (one was in response to a similar question involving receptive anal sex & a broken condom). He did caution about the lack of clinical data but based his response on an "educated guess". I subsequently re-read your responses to my question &, unless I am mistaken, believe that you were expressing the same view on the effectiveness of PEP (ie. highly effective but difficult to quantify) although you do not appear comfortable going as far as Dr Handsfield in providing a number (ie. "nearly 100%").

There was also another response to an "Ask the Experts" question on the risk of receptive anal sex which quantified the risk of a single episode of unprotected receptive anal intercourse at 1 in 250 when the insertive partner is known to be HIV positive (citing a CDC survey).

Given this information, would it be fair then to say that PEP initiation at 4½ to 5 hours post exposure (single episode of receptive anal intercourse with an insertive partner of unknown HIV status involving a broken condom) be considered to be highly effective?

Thanks. This should close off my question.

Edward W. Hook M.D.

50 months ago

I agree with your summary. PEP is highly effective and the sooner it is started follow risky exposure, the better. There is little doubt that PrEP including PrEP on demand is more effective than PEP but all three approaches to prevention are highly effective.

I’m please my comments have been helpful. This thread will no be closed. EWH

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