[Question #11261] PEP Time to Initiation After Exposure

15 months ago

Today, I was prescribed a 28-day course of generic Truvada as well as Tivicay for PEP. Potential exposure occurred just last night/early morning (about 3:00 a.m.), so it has not been 24 hours yet. Sadly, I’m traveling and the location I’m in has no Tivicay available — anywhere. I tried all pharmacies and even inquired at the small hospital ER. The pharmacies did have the generic Truvada, which I had filled. I’ll be able to get Tivicay tomorrow when I get home, so that will be about 36 hours post exposure. Two questions: (1) should I start the truvada now or should I wait until tomorrow when I have the Tivicay; and (2) is PEP at 36 hours post exposure still highly effective (assuming adherence and no further risk exposures)?

H. Hunter Handsfield, MD

15 months ago

Welcome to the forum. Thanks for your question.

The addition of dolutegravir (Tivicay) to emtricitabine plus tenofovir (Truvada) for PEP is only a modest improvement; Truvada alone is highly effective.

1) Ideally you should speak with the prescribing doctor or clinic for their advice. But if that's not practical, I'm confident they would advise starting the Truvada now, and the second drug when you get it.

2) There aren't very good hour-by-hour data on PEP effectiveness, but it's highly effective within 48 hours. I would expect starting at 36 hr to be very reliable. But as per answer no. 1, if you start Truvada now, I would count that as the time to onset of PEP.

You say nothing about the exposure you are concerned about. Perhaps I would have additional advice if you'd like to provide some information about it. In the meantime, I hope this information is helpful. Let me know if anything isn't clear.

HHH, MD

---

15 months ago

Thank you, Dr. Handsfield! That is very helpful. My exposure was to receptive anal intercourse from another male. This was, of course, unexpected and unplanned and a poor decision. I am a 40 year old male, old enough to know better. I will take the first dose of Truvada tonight, and that will be within 24 hours. Tomorrow, after I land at the airport, my first stop will be at the pharmacy to pick up the Tivicay. Thanks again for the clear advice!

H. Hunter Handsfield, MD

15 months ago

Thanks for the additional info. Your plan is solid and you can expect PEP to be effective. Also remember that even if your partner has untreated HIV, the odds still are greatly in your favor even without PEP -- under 1% chance you would be infected. And if you estimate a 10% chance your partner is infected, your odds are one chance in a thousand (without PEP). So don't lose too much sleep over this! (And if you can contact him, your partner might have reassuring information about his HIV status.)---

15 months ago

Thank you again for the clear answers. You and Dr. Hook do wonderful work on this forum.

As I think I have one additional follow up question, I was hoping you’d indulge me here.

I took my first dose of FTC/TDF approximately 21 hrs. post exposure. The following day when I returned home, I took the second dose of FTC/TDF in combination with DTG (40 hrs. post exposure).

The timing and differing mechanisms of action of the two drug classes — NRTIs and INSTIs— triggered a look into the viral life cycle.

I ran across a study whose conclusion seems to support PEP effectiveness up until 33 to 52 hours post exposure: https://journals.asm.org/doi/10.1128/jvi.05095-11.

The study’s methods are beyond my understanding. That said, the authors examine the time it takes HIV to complete its life cycle in productively infected CD4+ T cells. Specifically they compare the time it takes in vitro versus in vivo. In vivo, the life cycle is longer. It’s 52 hrs, with 33 hrs of that being taken up by reverse transcription.

If reverse transcription takes 33 hrs, wouldn’t this imply (in theory) that an NRTI started at within 33 hrs of exposure would be very highly effective (fingers crossed!)?

15 months ago

I hasten to add that the above was my final question. I don’t want to give the impression of being overly anxious, as so many are on this forum. Thank you again for the fine and invaluable resource you provide here.

H. Hunter Handsfield, MD

15 months ago

You're more into the weeds on these issues than I am. I'm quite certain that the exact timing of your two drugs for PEP doesn't matter -- assuming that's your concern. And I don't know enough about HIV biology or the mechanism of action of the ARVs to judge your statement that treatment with an NRTI within 33 hours would enhance efficacy. It's a moot point: I don't see how it would be possible to design a study to prove the point, and I really don't think it matters, in few of currently available study results.

That completes the two follow-up exchanges included with each question and so ends this thread. I hope the discussion has been helpful, even though I couldn't answer your last question in the detail you might have hoped.

Best wishes and say safe.

---