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/
------------------------------
Dan Scales PharmD, AAHIVP
Director of Pharmacy Collaborative Care
Vivent Health
------------------------------
Original Message:
Sent: 04-01-2022 10:09
From: Kara McGee
Subject: switching oral PrEP to CAB
I wish I knew the answer to this but I can't find any data about tissue levels for CAB.
------------------------------
Kara McGee
Duke Health Infectious Diseases Clinic
Durham NC
Original Message:
Sent: 03-30-2022 20:19
From: Adam Zweig
Subject: switching oral PrEP to CAB
Kara,
Do we know if serum levels equate with protection, or do we think that tissue levels are also important?
------------------------------
Adam Zweig
AIDS Healthcare Foundation
San Diego CA
Original Message:
Sent: 03-30-2022 15:11
From: Jeffrey Kirchner
Subject: switching oral PrEP to CAB
This is helpful Kara - just got 2 questions from clinic on this today including a shocking note that one of our Medicaid plans in PA - is covering Apretude.
------------------------------
Jeffrey Kirchner
Lancaster PA
Original Message:
Sent: 03-29-2022 11:48
From: Kara McGee
Subject: switching oral PrEP to CAB
I talked with some of my colleagues who understand the CAB PK data better than I do and they feel that 7 days of oral TDF/FTC or TAF/FTC after CAB injection is a reasonable approach. There is no data so an "official" recommendation is not possible yet.
Here is the summary of the PK data that they gave me:
"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 McGee
Duke Health Infectious Diseases Clinic
Durham NC
Original Message:
Sent: 03-25-2022 20:55
From: Julia Cooper
Subject: switching oral PrEP to CAB
A 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
------------------------------