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  • 1.  Resistance Testing Interpretation and ART Recommendations

    Posted 12 days ago

    Hello,

    We had a patient establish care in our clinic with an extremely complicated history. Patient's a 60 yo AA male. Current VL 325,000 copies (12/2025) and CD4 abs 55 (12/2025). sCR 1 / eGFR 86 and normal hepatic function. Additional information below from what I could gather from outside records:

    ART History: Dx 1998
    • Trizivir (abacavir/lamivudine/zidovudine), Raltegravir, boosted Darunavir (7/2009-4/2014)
    • Combivir, Raltegravir, Rilpivirine (4/2014-2/2015)
    • Combivir, Dolutegravir, Rilpivirine (2/2015-4/2016)
    • Prezcobix, Dolutegravir, Rilpivirine (4/2016 - 10/2020)
    • Dolutegravir, darunavir/r bid + doravirine 10/2020 [based on genotype analysis 7/15/2020]
    • Fostemsavir, Dolutegravir, Doravirine (7/2020 - 12/2025)

    Genotype Summary: 
    11/9/2000 RTI 184V, 211K, 214F, PI 36I, 47V, 82A 
    1/13/2005 RTI: 67N/D, 65R, 219Q, 103N, PI: 20R, 32I, 36I, 63P, 71I/V, 82A 
    5/13/2013: not detected (RT-PR and integrase)
    5/12/2015: RT GENE MUTATIONS: R211K , PR GENE MUTATIONS: M36I,L63P,V77I/V
    4/12/2016 (VL 32,700): wild type virus indicating non compliant.
    5/22/2020: K101K/E, R211K, I13V, L63P, V77I/V
    10/11/22: wild type virus
     
    Stanford Drug Resistance Summary: 
    Protease Inhibitors
    atazanavir/r (ATV/r)
    Intermediate Resistance
    darunavir/r (DRV/r)
    Intermediate Resistance
    lopinavir/r (LPV/r)
    High-Level Resistance
     
    Nucleoside Reverse Transcriptase Inhibitors
    abacavir (ABC)
    High-Level Resistance
    zidovudine (AZT)
    Susceptible
    emtricitabine (FTC)
    High-Level Resistance
    lamivudine (3TC)
    High-Level Resistance
    tenofovir (TDF)
    Intermediate Resistance
     
    Non-nucleoside Reverse Transcriptase Inhibitors
    doravirine (DOR)
    Susceptible
    efavirenz (EFV)
    High-Level Resistance
    etravirine (ETR)
    Potential Low-Level Resistance
    nevirapine (NVP)
    High-Level Resistance
    rilpivirine (RPV)
    Intermediate Resistance

    Given his complicated oral regimen and extensive resistance patterns, we obtained a phenotype in 12/2025 during his establishing care visit. That just came back as pan-sensitive. My questions:

    1. Since it's a phenotype, can we truly use any ARV and restart him on a STR?
    2. Or do we still need to consider that WT virus likely took over causing this pan-sensitive result?

    Our hope is to eventually get him on to LAIs because he is so pill averse, but any guidance, thoughts, or recommendations would be much appreciated!



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    Rachel Marchi
    Saint Louis MO
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  • 2.  RE: Resistance Testing Interpretation and ART Recommendations

    Posted 11 days ago

    You cannot trust the phenotype in this case. Phenotypes can be useful in predicting resistance to drugs and drug classes the patient is currently taking, but a cumulative genotype like the one you have is much more accurate at telling you about resistance that has accumulated over the years. Phenotypes are inferior to genotypes at predicting resistance when mixtures of mutant and wild-type virus are present, which is often the case for drugs or drug classes that are no longer being taken.

    I see that he's taken INSTIs but there is no INSTI resistance shown in the results. At one time, you had to order INSTI genotypes separately, and I'm wondering whether they were included in the genotypes listed.  If he's really pill averse, then the combination of LEN + CAB might be appealing, but if he's developed resistance to DTG, that wouldn't work. It sounds like he hasn't had a genotype checked in several years.  If he's still taking a DTG-containing regimen, I would order one now.



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    Joel Gallant, MD, MPH
    Johns Hopkins University
    Baltimore, MD

    AXCES Research Group
    Santa Fe, NM
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