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switching oral PrEP to CAB

  • 1.  switching oral PrEP to CAB

    Posted 03-28-2022 09:08
    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?

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    Julia Cooper MD, AAHIVS
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  • 2.  RE: switching oral PrEP to CAB

    Posted 03-28-2022 17:09
    That's correct, Julia.  We don't know how much time it takes after injection to reach adequate tissue levels for Apretude to prevent HIV infection, and there is no guidance currently in the package insert.  So, maybe it would be smart to continue oral PrEP for a week or so after the initial injection, if possible.  Or, perhaps encourage consistent condom use, at least during that time period.  We do know that in the HPTN trials, seroconversion soon after the initial injection (in those newly started on PrEP) was rare.  So, that is certainly comforting.

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    Adam Zweig
    AIDS Healthcare Foundation
    San Diego CA
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  • 3.  RE: switching oral PrEP to CAB

    Posted 03-29-2022 09:19
    Edited by Dan Ebeling 03-29-2022 09:19
    Excellent question.
    As in the many clinical trials an oral lead-in of 4 weeks was used to attain a protective serum level of CAB prior to first injection.
    I would guess that the same pattern should be followed in this case.
    The PK of CAB for PrEP has been published. This information can help guide you in how long the TVD should be continued.
    David  


    W. David Hardy, MD, AAHIVS

    Scientific and Medical Consultant

    6123 Maryland Drive

    Los Angeles, California 90048-4735

    E-mail: WDAVIDHARDYMD@GMAIL.COM

    Telephone: 310-709-3505 (Mobile)


     

     






  • 4.  RE: switching oral PrEP to CAB

    Posted 03-29-2022 11:55
    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



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    Kara McGee
    Duke Health Infectious Diseases Clinic
    Durham NC
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  • 5.  RE: switching oral PrEP to CAB

    Posted 03-30-2022 16:47
    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.

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    Jeffrey Kirchner
    Lancaster PA
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  • 6.  RE: switching oral PrEP to CAB

    Posted 03-31-2022 10:05
    Kara,

    Do we know if serum levels equate with protection, or do we think that tissue levels are also important?

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    Adam Zweig
    AIDS Healthcare Foundation
    San Diego CA
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  • 7.  RE: switching oral PrEP to CAB

    Posted 03-31-2022 17:03
    Kara or David,
    Do we have PK information for cab without oral lead in? I have not been able to find.  I think tissue levels are likely important and my understanding of second bolus dosing was that it was required for adequate depot development and tissue concentrations.  
    Thanks all.  Very good discussion!

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    Dan Scales PharmD, AAHIVP
    Director of Pharmacy Collaborative Care
    Vivent Health
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  • 8.  RE: switching oral PrEP to CAB

    Posted 04-01-2022 10:00

    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.

    LINK:  https://journals.lww.com/co-hivandaids/Fulltext/2015/07000/Formulation_and_pharmacology_of_long_acting.7.aspx



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    Ashwin Gupta
    Philadelphia PA
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  • 9.  RE: switching oral PrEP to CAB

    Posted 04-01-2022 20:38
    If there is one person on Earth who knows about the PK of cabotegravir (IM and oral), it would be:

    William Spreen

    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.



    W. David Hardy, MD, AAHIVS

    Scientific and Medical Consultant

    6123 Maryland Drive

    Los Angeles, California 90048-4735

    E-mail: WDAVIDHARDYMD@GMAIL.COM

    Telephone: 310-709-3505 (Mobile)










  • 10.  RE: switching oral PrEP to CAB

    Posted 04-01-2022 10:19
    I wish I knew the answer to this but I can't find any data about tissue levels for CAB.

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    Kara McGee
    Duke Health Infectious Diseases Clinic
    Durham NC
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  • 11.  RE: switching oral PrEP to CAB

    Posted 04-01-2022 11:39

    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/



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    Dan Scales PharmD, AAHIVP
    Director of Pharmacy Collaborative Care
    Vivent Health
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  • 12.  RE: switching oral PrEP to CAB

    Posted 04-04-2022 09:06
    I've been following this conversation as I think these concerns and questions are being discussed by a lot of clinicians who are unsure how to move forward with the recommendation for patients to opt out of the oral lead-in. I'm very concerned about this and Dan Scales thank you for making this make sense and presenting the real challenge with CAB for PrEP. 

    So, with data showing seroconversion in CAB having delayed diagnosis is this a wise decision to opt out of the oral lead in given the tight window Dan Scales presented? I'm not sure how I feel about this as we have no data to support skipping oral lead in as a good idea.

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    Michelle Ogle
    Bronx NY
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  • 13.  RE: switching oral PrEP to CAB

    Posted 04-19-2022 10:02
    Hi all,

    There was a tissue PK study with CAB.

    Here's the summary from ViiV, but it has the citation to the original article. 

    https://d201nm4szfwn7c.cloudfront.net/5f95dbd7-245e-4e65-9f36-1a99e28e5bba/2a0aab8d-dfee-48b1-89e4-99de93d46741/2a0aab8d-dfee-48b1-89e4-99de93d46741_viewable_rendition__v.pdf?medcommid=MED--US-8368

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    Katy Garrett
    Lexington KY
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  • 14.  RE: switching oral PrEP to CAB

    Posted 21 days ago

    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?  

    Chris

    (Oh, and conventional oral TFV-based PrEP vs. optional oral Cab lead in - that's another thread.)



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    Christopher Hall
    East Bay AIDS Center
    Santa Rosa CA
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