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  • 1.  Changing ARV with multiple resistances

    Posted 02-16-2022 03:54

    Hello all.   My name is Myra, FNP.  I work in the lovely Windy City. 
    I would love to have some input on this case.

    Pt is on Descovy + Prezcobix and Bactrim for PCP proph. 
    CD4 176 % 8.8 and VL 60.  May miss 1-2 doses per month.
    Below is his genosure.   

    Is it ok to keep him on his regimen given he has two active drugs and prezcobix has a high resistance barrier?

    Thank you and I look forward to the feedback!

    --------------------------   ----------           --------
    Abacavir        Ziagen       Sensitive
       RAMs*: M184M/V
    Didanosine      Videx         Resistance Possible
       RAMs*: M184M/V
    Emtricitabine   Emtriva       Resistant
       RAMs*: M184M/V
    Lamivudine      Epivir        Resistant
       RAMs*: M184M/V
    Stavudine       Zerit        Sensitive                   1
       RAMs*: None
    Tenofovir       Viread       Sensitive                   2
       RAMs*: None
    Zidovudine      Retrovir     Sensitive                   2
       RAMs*: None
    Doravirine      Pifeltro      Resistance Possible
       RAMs*: K103K/N, D177D/N, Y181Y/C, G190G/A, H221Y,
    Efavirenz       Sustiva       Resistant
       RAMs*: K103K/N, Y181Y/C, G190G/A
    Etravirine      Intelence     Resistance Possible
       RAMs*: Y181Y/C, H221Y
    Nevirapine      Viramune      Resistant
       RAMs*: K103K/N, Y181Y/C, G190G/A
    Rilpivirine     Edurant       Resistant
       RAMs*: K103K/N, Y181Y/C, H221Y
    Bictegravir     Bictegravir  Sensitive
       RAMs*: None
    Dolutegravir    Tivicay      Sensitive
       RAMs*: None
    Elvitegravir    Vitekta      Sensitive
       RAMs*: None
    Raltegravir     Isentress    Sensitive
       RAMs*: None
    Atazanavir/r    Reyataz / r   Resistant
       RAMs*: K20K/V, M36I, K43K/T, M46M/I, I54I/V, D60E,
              I62I/V, A71A/V, G73G/S, V82V/A, L90L/M
    Darunavir/r     Prezista / r Sensitive
       RAMs*: E35E/N, K43K/T, M46M/I, G73G/S, L90L/M
    Fosamprenavir/r Lexiva / r    Resistant
       RAMs*: E35E/N, K43K/T, M46M/I, I54I/V, G73G/S, V82V/A,
    Indinavir/r     Crixivan / r  Resistant
       RAMs*: E35E/N, M36I, M46M/I, I54I/V, A71A/V, G73G/S,
              V82V/A, L90L/M
    Lopinavir       Kaletra       Resistant
       RAMs*: E35E/N, K43K/T, M46M/I, I54I/V, A71A/V, G73G/S,
              V82V/A, L90L/M
    Nelfinavir      Viracept      Resistant
       RAMs*: M36I, M46M/I, I54I/V, A71A/V, G73G/S, V82V/A,
    Ritonavir       Norvir        Resistant
       RAMs*: K20K/V, K43K/T, I54I/V, A71A/V, G73G/S, V82V/A,
    Saquinavir/r    Invirase / r  Resistant
       RAMs*: K20K/V, E35E/N, K43K/T, I54I/V, I62I/V, A71A/V,
              G73G/S, L90L/M
    Tipranavir/r    Aptivus / r   Resistance Possible
       RAMs*: E35E/N, M36I, K43K/T, I54I/V, A71A/V, L90L/M
    *RAMs = Resistance Associated Mutations observed
    Summary of Mutations Observed:
    RT: P9P/S, K20K/R, V35V/I, S48T, S68S/G, Q102K/R, K103K/N,
        K122P, I142I/V, C162S, D177D/N, Y181Y/C, M184M/V,
        G190G/A, Q197E, T200A, I202V, E204E/K, H221Y, E233E/D,
        P243S, V245V/E, D250D/E/K/N, R277K, T286A, A288S,
        V293I, E297E/G, V317V/A, Q334Q/H, M357T, K358R,
        A360A/V, A376S, T386I, K390R, A400S
    IN: K14K/R, R20K, K34R, V72I, L101I, V113I, S119S/P, K156N,
        V201I, V234L, D256E
    PR: K20K/V, E35E/N, M36I, K43K/T, M46M/I, I54I/V, R57K,
        D60E, I62I/V, L63P/S, I64I/V, C67C/F, A71A/V, I72I/T,
        G73G/S, V82V/A, L90L/M
    Assessment of drug susceptibility is based upon detected
    mutations and interpreted using an advanced proprietary
    algorithm (version 18).
     1 - Assessment for this drug was derived considering the
    sensitizing effect of mutation M184V.
     2 - Assessment for this drug was derived considering the
    sensitizing effect of mutations Y181C and M184V.
    HIV genosure archive interp
    Interpretation algorithms for ritonavir-boosted protease
    inhibitors appropriate for the following dosages: AMP/r
    600mg/100mg BID; ATV/r 300mg/100mg QD; IDV/r 800mg/200mg
    BID; LPV/r 400mg/100mg BID; SQV/r 1000mg/100mg BID; TPV/r
    500mg/200mg BID; and DRV/r 600mg/100mg BID.

    Myra Sikwata
    Burns Harbor IN

  • 2.  RE: Changing ARV with multiple resistances

    Posted 02-16-2022 15:17
    This is an interesting case. First this person is highly experienced and probably misses more doses than they are saying. They have what's called mixtures on their resistance meaning some of the virus is sensitive and some is resistant indicating either they just started taking Meds again or start and stop often. So this regimen is QD darunavir and although the resistance test says it's sensitive they actually have 1 major darunavir mutation, the G73S, thus based on clinical trials, this person should really be in BID Darunavir, which would mean they couldn't be in prezcobix, because that's 800mg co formulated with cobi, so if you are a purest this person should be in 600 DRV and 100 norvir. -- so now this is going to be how comfortable do you feel with this mutation pattern and his almost suppression. Personally, I would change the regimen to Symtuza/Tivicay. This would give the protection to the DRV that is starting to be compromised, but would still keep the regimen a once daily two pill, vs changing to a BID multi pill regimen.

    Angela Kapalko
    Physician Assistant Chairperson for AAHIVM
    Philadelphia FIGHT CommunityHealth Centers
    Philadelphia PA

  • 3.  RE: Changing ARV with multiple resistances

    Posted 02-16-2022 15:17
    Edited by George Froehle 02-16-2022 15:23

  • 4.  RE: Changing ARV with multiple resistances

    Posted 02-16-2022 16:28
    Dear Myra,
    Just one question, why isn't this patient receiving an InSTI-containing regimen, e.g., BIC/TAF/FTC?
    W. David Hardy, MD
    Scientific and Medical Consultant
    310-709-3505 (Mobile)

  • 5.  RE: Changing ARV with multiple resistances

    Posted 02-16-2022 19:57
    With VL of 60, if the VL is stable I would not change therapy.


    Peter Shalit, MD, PhD, FACP, AAHIVS 
    Cabrini Tower, 901 Boren Ave Suite 850, Seattle, WA 98104 
    P 206-624-0688 F 206-624-2432  

  • 6.  RE: Changing ARV with multiple resistances

    Posted 02-16-2022 23:44
    Hi Myra:
    This is a great case, thanks for sharing.  Just curious, is this a recent infection with only this genotype, or has the patient been HIV+ for a long time with other regimens previously?  Secondly, does he need the PCP prophylaxis?  I think regardless, keeping him on Prezcobix + Descovy (or better yet, Symtuza since it's single tablet) would probably be fine but as Dr. Kapalko has pointed out, he should probably be on BID darunavir if you want to stay with a PI-based regimen given the G73S mutation.  However, I agree with Dr. Hardy, I'd switch him to Biktarvy.  Maybe switching to single tablet with less drug interactions is the right way to go, and resistance barrier shouldn't decrease from switch of PI to Integrase Inhibitor.  And if his VL has been suppressed for over 3-6 months, I'd discontinue the Bactrim.  Thanks for a nice case,

    James Adams
    Rancho Mirage CA