W. David Hardy, MD, AAHIVS
Scientific and Medical Consultant
Los Angeles, California 90048-4735
Telephone: 310-709-3505 (Mobile)
"PK data for CAB suggests that the median time to 8x PA IC90 is 2 days after injection (irrespective of oral lead in), and 95% of people had 8x PAIC90 by 7 days post first injection."Thanks for posting this - I suspect this is one of many questions others have about switching to CAB.Kara
------------------------------Kara McGeeDuke Health Infectious Diseases ClinicDurham NC------------------------------
------------------------------Kara McGeeDuke Health Infectious Diseases ClinicDurham NCOriginal Message:Sent: 03-25-2022 20:55From: Julia CooperSubject: switching oral PrEP to CABA patient who was taking TDF/FTC for PrEP and is switching to injected Cabotegravir, and who opted to skip the oral CAB lead-in, asked me an excellent question. After reading that the precise lag time from CAB injection to adequate protection is unknown, he asked whether he should continue the TDF/FTC for a few days to overlap the first CAB injection. Any thoughts about how you will advise people making this switch?------------------------------Julia Cooper MD, AAHIVS------------------------------
This has already been a great discussion thus far!I have had two patients ask me about this exact situation (switching from TDF/FTC)1. I am also typing from the commonwealth of Pennsylvania, though in a different region as Jeffrey, cabotegravir is on universal PDL here. And, to my understanding, irrespective of treatment vs PrEP.
2. Seems like a throwback article circa 2015, but I am hoping I can obtain some updated PK information. I have asked someone local to send me an update if there is one out there to look over-- great to know if Adam's question can be answered, as well.
Bill Spreen, Pharm.D, is a Director of Research and Development at ViiV Healthcare and based in Research Triangle Park, North Carolina. Currently, he is Medicine Development Leader for the HIV integrase inhibitor cabotegravir, a long-acting injectable agent under investigation for both HIV prevention and treatment.
Hey all, I have some information, but don't have the citation, sorry. Tissue concentrations are correlative to serum, which is great news. The data on PK/serum concentrations oral lead in vs without is less exciting. With oral lead in post first dose mean serum concentration is several times therapeutic levels (which is defined as 0.66 microg/ml) and remains thus for about 8 weeks, and the entire 95% confidence interval includes said therapeutic level. Without oral lead in, cab reaches the therapeutic level at day ~4x therapeutic level at day 1, falls to ~2 times by week one, and is pretty much exactly 0.66 microgram by week 4. The confidence interval without never fully encapsulates the 0.66 microgram/ml serum level.
So week 1 would appear to be pretty well protected, but by week 3/4 post first dose without oral lead in, it's running pretty tight. I also understand that the therapeutic level is 4X90% inhibitory concentration, so 0.66 is already working in some wiggle room, but there definitely seems to be some risk that whole first month unless you opt for oral lead in.Below is a link to some of the data, and if I can track down the citation for the rest I'll post here. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638427/
Hi Kara et al -- I'm researching this issue of TFV-based oral PrEP switch to Cab-LA and this has been a super helpful thread...
Turns out that due to all the logistical challenges associated with securing Apretude, it seems to make more sense to get most amenable patients on conventional oral PrEP and then switch to the injectable if/when that becomes feasible. I suspect due to logistics alone, TFV-based oral PrEP lead in to Cab-LA may well become the norm...anyway...
Question: based on this discussion, if we believe it may be judicious to to continue TFV-based oral PrEP 4-7 days following the first injection (even though in 083 it was stopped on day of first injection), is there any reason to think there are anatomic/tissue differences that would alter that recommendation in those other than MSM/TGW who are at HIV risk via vaginal sex? My review of 083/084 observations says no, but why not ask?
(Oh, and conventional oral TFV-based PrEP vs. optional oral Cab lead in - that's another thread.)