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  • 1.  switching arv due to multiple resistance mutations

    Posted 04-14-2022 10:27
    hi everyone,
    i am a counselor for a female 62 yr old hiv pos since 2005 with a history of changing meds due to gastric issues . she has only ever been successful on complera and odefsey for any duration due to extreme nausea and vomiting . she has 10800 viral load and 500 t cell but has done so taking 1/2 dose and 3//4 dose now genosure shows mutations . she is requesting Bictarvey but docs recommend cobistat and tivicay ...how do i counsel this woman who has basically looked at the doc and said refer me to hospice i cant live this way...subligual zofran is being utilised also .....would bictarvey be a better bet since she has such history ....here is her data and she has agreed to take the full dose of the bicktarvey .....

    HIV-1 Subtype: B

    Drug Genotypic

    Generic Name Brand Name Assessment Comments

    -------------------------- ---------- --------

    NRTI

    Abacavir Ziagen Resistant

    RAMs*: M41L, L74I, M184V, K219R

    Didanosine Videx Resistant

    RAMs*: M41L, L74I, M184V

    Emtricitabine Emtriva Resistant

    RAMs*: M41L, M184V, K219R

    Lamivudine Epivir Resistant

    RAMs*: M41L, M184V, K219R

    Stavudine Zerit Resistant 1

    RAMs*: M41L, K70N, K219R

    Tenofovir Viread Resistance Possible 1

    RAMs*: M41L, K219R

    Zidovudine Retrovir Resistant 1

    RAMs*: M41L, K219R

    NNRTI

    Doravirine Pifeltro Resistance Possible

    RAMs*: K101D, V108I, E138Q, E203K, L228R

    Efavirenz Sustiva Sensitive

    RAMs*: V108I

    Etravirine

    Intelence Resistant

    RAMs*: E138Q, Y181I

    Nevirapine Viramune Resistant

    RAMs*: V108I, E138Q, Y181I

    Rilpivirine Edurant Resistant

    RAMs*: E138Q, Y181I

    INI

    Bictegravir Bictegravir Sensitive

    RAMs*: None

    Dolutegravir Tivicay Sensitive

    RAMs*: None

    Elvitegravir Vitekta Sensitive

    RAMs*: None

    Raltegravir Isentress Sensitive

    RAMs*: None

    PI

    Atazanavir/r Reyataz / r Sensitive

    RAMs*: None

    Darunavir/r Prezista / r Sensitive

    RAMs*: None

    Fosamprenavir/r Lexiva / r Sensitive

    RAMs*: None

    Indinavir/r Crixivan / r Sensitive

    RAMs*: None

    Lopinavir Kaletra Sensitive

    RAMs*: None

    Nelfinavir Viracept Sensitive

    RAMs*: None

    Ritonavir Norvir Sensitive

    RAMs*: None

    Saquinavir/r Invirase / r Sensitive

    RAMs*: None

    Tipranavir/r Aptivus / r Sensitive

    RAMs*: None

    *RAMs = Resistance Associated Mutations observed

    Summary of

    Mutations Observed:

    RT: V35L, M41L, K70N, L74I, K101D, Q102K, V108I, E138Q,

    Y181I, M184V, I195L, E203K, R211K, K219R, L228R, E248D,

    A272P, T286A, V292I, V293I, E297A

    IN: P90A, K111T, V113V/I, T124A, T125A, K173R, I203M,

    I208I/L, S230N, V234L, S283G

    PR: N37S, R41K, L63P



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    Deanne Carroll
    Wilmington NC
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  • 2.  RE: switching arv due to multiple resistance mutations

    Posted 04-15-2022 09:12

    This is actually a real tricky one, because there are so many factors in play. First, this provider who is prescribing meds for this patient is trying to make the best decisions based on their history and resistance pattern. Unfortunately this patient has ruined some options because of how they have taken meds, and even tho complera and odefsey seem to be the only ones that "worked" they didn't really work because they didn't take them all the time, have a high viral load AND developed resistance. So it might be the only regimen they identify as not getting sick from but it didn't work. 


    Instead of getting specific with this patient I will talk about one of mine to try and relate. I had a patient a number of years ago that ALWAYS had nausea with ANY hiv meds. All of em. But when we dug deeper it was actually a physical manifestation of her depression around her HIV and how it made her feel to think about the meds. Once we got her in therapy to work on that, she never had an issue with nausea again. 


    there are some patients that are booster intolerant. This is well written about. What this might mean is this patient will be on a multi pill, twice daily regimen Or even some pills but also maybe an infusion (like trogarzo). So I think some things to really talk to this patient about is what is THEIR goal with their HIV. Is it to be healthy? Is it to not have any side effects (who cares about number of pills just as long as no side effects)? Is their goal to never take meds cause they hate them all? What about liquid meds? So I think trying to identify the patients goals might actually help come to some of the reasons this patient is struggling so much with meds. Because something tells me it's not about the pill or pills but the diagnosis itself that might be playing a large part in this and no matter what you try, it's going to end poorly. 


    if this were my patient, and just looking at the resistance I would be hesitant to do biktarvy because there are multiple NRTI mutations and then bictegravir would be the only real active agent. 



    ------------------------------
    Angela Kapalko
    Physician Assistant Chairperson for AAHIVM
    Philadelphia FIGHT CommunityHealth Centers
    Philadelphia PA
    akapalko@fight.org
    ------------------------------



  • 3.  RE: switching arv due to multiple resistance mutations

    Posted 04-15-2022 18:29
    Thank You for your input very much !

    ------------------------------
    Deanne Carroll
    Wilmington NC
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  • 4.  RE: switching arv due to multiple resistance mutations

    Posted 04-15-2022 17:43
    I think that Biktarvy would have a good chance of working.  The bictegravir has full activity, and the virus would be sensitized  to TAF due to the presence of the M184V.  But, the TAMs will reduce the tenofovir sensitivity.   So, you might want to use Biktarvy, and add another agent with a novel MOA, such as fostemsavir, to provide a level of confidence.  Good luck!

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    Adam Zweig
    AIDS Healthcare Foundation
    San Diego CA
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  • 5.  RE: switching arv due to multiple resistance mutations

    Posted 04-19-2022 09:50
    I'd love to have more information if possible.

    What is her underlying gastric issue? Is it nausea/vomiting only? Or does she have a need for a PPI? Can she take other meds and just has issues with the HIV medications? Aside from zofran, what other meds is she taking? What is her HIV treatment history? She's 62, so I'd think cardiovascular disease and diabetes would be likely possibilities to think about co-morbidities and concomitant medications. She apparently tolerated Odefsey and Complera but has resistance, which would suggest she didn't take them routinely and/or correctly (again makes me think maybe a PPI or something is involved). Or maybe she has short gut or something impairing her absorption???

    All that being said, from a purely genotype standpoint, Biktarvy *should* be fine. There's a fair amount of data showing Biktarvy viral suppression even with resistance mutations. Granted, that's retrospective and can make people nervous to adopt in practice. So adding an additional drug could make people a lot more comfortable.  Doravirine isn't fully active but is the most active of the NNRTIs so it could provide a nice 'boost'. If she's not taking acid suppression, the unbooted atazanavir dosing could work. There's not any documented PI resistance and that'd avoid the ritonavir or cobicistat which are more likely the causes of nausea. Someone else suggested fostemsavir which makes a lot of sense too. Odds are slim, but if you'd want to use Maraviroc, you can get a trophile and see if it's an option.

    Another option that I like when you have limited drug choices, is to get a phenotype. It's a pretty rare tests these days, but can be useful when your drug options are limited for one reason or another. That could also help people feel confident in the Biktarvy alone, assuming it shows good activity. 

    On the plus side, with a CD4 of 500, she's in a pretty good spot. Having had HIV for at least 17 years and intermittent adherence, I think that's remarkable. Most people I can think of in these situations have much weaker immune systems, so I want to acknowledge the effort she has put in. That actually buys you all some time for additional counseling, testing, and waiting for her to be ready to take meds.

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    Katy Garrett
    Lexington KY
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  • 6.  RE: switching arv due to multiple resistance mutations

    Posted 04-19-2022 12:17

    Thanks so much katy She has long occuring gastric issues on and off hiv meds. She went thru a list as long as my arm and ended up w Dr Gahuna at John Hopkins in Baltimore. there she was put on complera and isentress .She was told there to take what she could take successfully and work up to a full dose . She states she took a half complera only until switched to odefsey due to bone scan results being poor . The patient was told she had bones similar to an 80 yr old at that point( 5 years ago). She has been extensively counseled on medication compliance and resistance possibilities. She take ppi several times a week but not daily due to a hiatal hernia diagnosed w endoscopy and has esophageal bleeding in the early nineties which was fully treated at the time.  She takes some pain meds and seems to handle that w the zofran. She states she has not had another endoscopic since then but has always been super sensitive to any medications. She takes metoprolol for pvcs causing irregular heart rhythm and seems to be increasingly affected by caffeine/occasional etoh use . She also has hep c .She had a heart test in the last year that showed only some minor calcification of her aorta. I had an appt with her this am so was able to gather more info. She is on a daily valtrex 500 mil to prevent herpes/shingles outbreak. She has been off meds for a month and is reporting some itching/and inflammation in old orthopedic injuries. Thank you so much for your input ! I hate to see this woman give up when she was doing ok in many ways but has always wanted quality of life over quantity ...She still has a boat and walks for exercise.....



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    Deanne Carroll
    Wilmington NC
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