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  • 1.  Confused regarding M184 RAM

    Posted 10-20-2022 23:36
    Hello all,
    28YO AAM Dx with HIV early 2021 and started on Trimumeq but off x 8 months.  Started him on Bictarvy 4/2022 with labs follows:
    4/12/22 CD4 60 VL 124000000
    6/16/22 CD4 431 VL 430
    9/01/22 CD4 426 VL 5,170
    The HIV-1 GenoSure PRIme(R) for this specimen has been completed.
    GenoSure PRIme(R)
    HIV-1 Subtype: B
    Drug                         Genotypic
    Generic Name    Brand Name   Assessment           Comments
    --------------------------   ----------           --------
    Abacavir        Ziagen       Sensitive
       RAMs*: M184V
    Didanosine      Videx         Resistance Possible
       RAMs*: M184V
    Emtricitabine   Emtriva       Resistant
       RAMs*: M184V
    Lamivudine      Epivir        Resistant
       RAMs*: M184V
    Stavudine       Zerit        Sensitive                   1
       RAMs*: None
    Tenofovir       Viread       Sensitive                   1
       RAMs*: None
    Zidovudine      Retrovir     Sensitive                   1
       RAMs*: None
    Doravirine      Pifeltro     Sensitive
       RAMs*: Q207E
    Efavirenz       Sustiva      Sensitive
       RAMs*: None
    Etravirine      Intelence    Sensitive
       RAMs*: None
    Nevirapine      Viramune     Sensitive
       RAMs*: None
    Rilpivirine     Edurant      Sensitive
       RAMs*: None
    Bictegravir     Bictegravir  Sensitive
       RAMs*: None
    Dolutegravir    Tivicay      Sensitive
       RAMs*: None
    Elvitegravir    Vitekta      Sensitive
       RAMs*: None
    Raltegravir     Isentress    Sensitive
       RAMs*: None
    Atazanavir/r    Reyataz / r  Sensitive
       RAMs*: L10I, M36I, I62V
    Darunavir/r     Prezista / r Sensitive
       RAMs*: L10I
    Fosamprenavir/r Lexiva / r   Sensitive
       RAMs*: L10I
    Indinavir/r     Crixivan / r Sensitive
       RAMs*: L10I, M36I
    Lopinavir       Kaletra      Sensitive
       RAMs*: L10I
    Nelfinavir      Viracept     Sensitive
       RAMs*: L10I, M36I
    Ritonavir       Norvir       Sensitive
       RAMs*: L10I
    Saquinavir/r    Invirase / r Sensitive
       RAMs*: L10I, I62V
    Tipranavir/r    Aptivus / r  Sensitive
       RAMs*: M36I
    *RAMs = Resistance Associated Mutations observed
    Summary of Mutations Observed:
    RT: T27S, V35I, Q102K, K122E, D123E, I135V, Q174K, M184V,
        G196E, T200I, Q207E, V245M, E248Q, D250E, A272P, R277K,
        T286A, E297K
    IN: S17N, V31I, K42K/R, H51Y, V72I, V113I, S119P, T122I,
        T124A, T125A, E198Q, V201I, K219N, N222K, V234L, S283D
    PR: L10I, L19I, M36I, N37D, R41K, I62V, L63P, I64L, I93L
    Genotype Comments (clinical significance may vary)
     1 - Assessment for this drug was derived considering the
    sensitizing effect of mutation M184V.
    Assessment of drug susceptibility is based upon detected
    mutations and interpreted using an advanced proprietary
    algorithm (version 18).
    HIV genosure prime(R) 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.
    Mixtures are indicated by amino acids separated by a slash.
    Assay Performance Characteristics
    - Assay is highly reproducible and sufficiently sensitive
    to allow testing of patient samples with viral loads as low
    as 500 copies/mL.
    - Detects mixtures of wild-type and drug-resistant viruses
    when present at levels as low as 10% of the total
    - Uses Monogram's HIV genotyping algorithm, which is based
    on a large database of over 100,000 matched HIV
    genotype-phenotype results and is reviewed and updated on a
    regular basis.
    - Includes HIV-1 subtype which provides information that
    can be important for long-term drug treatment strategy and
    genotype interpretation.
    For more information on interpreting this report, please
    call LabCorp Customer Service at 800-762-4344 between the
    hours of 7:00am to 6:30pm EST Monday through Friday or
    8:00am to 5:00pm EST Saturday.
    GenoSure PRIme is a DNA sequence assay based on primer
    extension and chain termination that analyzes the protease
    (amino acids 1-99), reverse transcriptase (amino acids
    1-320) and integrase (amino acids 1-288) coding regions in
    HIV-1. Subtype is determined using the protease and reverse
    transcriptase sequence information. This test is validated
    for testing specimens with HIV-1 viral loads equal to or
    above 500 copies/mL and should be interpreted only on such
    specimens. This assay meets the standards for performance
    characteristics and all other quality control and assurance
    requirements established by CLIA. The results should not be
    used as the sole criteria for patient management. It has
    not been cleared or approved by the FDA. This document
    contains private and confidential health information
    protected by state and federal law. If you have received
    this document in error, please call 800-777-0177.
     I am confused about the M184 RAM.   Should I change his regimen or think it may be more of nonadherance?   He is not on any other prescription or OTC meds.

    Thanks in advance,


    Myra Sikwata
    Burns Harbor IN

  • 2.  RE: Confused regarding M184 RAM

    Posted 10-21-2022 12:37
    Should work even in setting of M184V.  I would suspect non adherence.

    Alexandra Danforth, PharmD, AAHIVP, BCACP
    Director, Infectious Disease and Clinical Pharmacy
    Trillium Health
    Rochester, NY

  • 3.  RE: Confused regarding M184 RAM

    Posted 10-21-2022 15:18

    I agree he is likely non-adherent however need to look for drug he taking multivitamins or minerals?

    Kevin Carmichael MD FIDSA
    Tucson, AZ

    Mobile 520.549.9338

  • 4.  RE: Confused regarding M184 RAM

    Posted 10-21-2022 21:58
    Thanks for the response.  He is only on Bicktarvy.

    Myra Sikwata
    Burns Harbor IN

  • 5.  RE: Confused regarding M184 RAM

    Posted 10-22-2022 18:20
    Recall the 184V mutation makes tenofovir a more powerful medicine.  In addition there is still a residual efficacy to FTC even with the 184 mutation.  In essence, he is still on over 2 effective meds and that should work.  Moke sure he is not taking divalent cations eg magnesium etc as bictegravir uses magnesium at its binding site.  Alternatively, if there is no drug interaction, then he is not taking his meds.  I tend to check a drug screen too as this is a reason why people don't take their meds.

    Michael Soles
    Los Angeles CA