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  • 1.  138A Mutation

    Posted 04-22-2024 15:35

    I have come across a question that I am not quite sure how to answer. 

    The E138A mutation which causes low level resistance to Rilpiverine also causes integrase resistance of either low level or potential when run through the Stanford Resistance Database and IAS-USA Mutation records. 

    However, when I am getting my genotypes back from State or Major Lab company it does not list the E138A as a concern in the Integrase reports. 

    My question is what am I missing here? Is this a concern or not. 

    I would never put someone with this mutation on Cabenuva or Juluca but is Dovato Ok? Should I be worried about this if I find someone on Dovato and change regime. 

    Should I be worked about other integrase combinations with triple drug therapy i.e. inst with dual nRTI therapy, esp lower level for resistance inst combinatiions? 

    Thanks in advance for your thoughts



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    [Jeffery][Dockery]
    [Physician]
    [Georgia][US]
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  • 2.  RE: 138A Mutation

    Posted 04-23-2024 18:00

    There are two different 138A mutations: one in reverse transcriptase and one in integrase.  There's no single 138A mutation that causes both NNRTI and integrase inhibitor resistance. It sounds like you're talking about the NNRTI mutation based on the lab report.

    Keep in mind that the presence of NNRTI mutations (and others as well) increases the likelihood that there also M184V, which may not be detected.  This would make me a little nervous about Dovato.



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    Joel Gallant, MD, MPH
    Santa Fe, NM
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  • 3.  RE: 138A Mutation

    Posted 30 days ago

    Thank you for the clarification. 

    I suspected it was two seperate location mutations but both named 138A (which is confusing) but had never came across it in this way in the past. Our reports from labs had changed and I had never had a client with the same mutation on both the Integrase and Regular genotypes.

    It is good to know about the 184V increased likelyhood. I will add it to my notebook. 

    Thank you for response. 



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    [Jeffery][Dockery]
    [Physician]
    [Georgia][US]
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  • 4.  RE: 138A Mutation

    Posted 30 days ago

    Per Stanford, E138 mutations alone do not reduce susceptibility to Integrase inhibitors. weighted genotypic score for CAB is 15, DTG is 10.  "The use of the combination of CAB/RPV should be considered to be relatively contraindicated."

    Susceptible: Total score 0 to 9, Potential low-level resistance: Total score 10 to 14, Low-level resistance: Total score 15 to 29 

    However in HPTN 083 There were 18/34 CAB  failures who develop 1 or more INSTI Mutations.                                          https://www.hptn.org/sites/default/files/inline-files/MarzinkeJID2021.pdf

     

    Also one of the risk failure for DTG resistance would be Dual therapy vs Triple therapy . Greater than 3 fold change is associated with 47% decreased in virologic response rate at week 48.

     

    For  RPV: E138A is a polymorphic mutation which reduces RPV susceptibility about 2-fold. weighted genotypic score 15. "The use of the combination of CAB/RPV should be considered to be relatively contraindicated."

     

    One of the biggest  predictors of virologic failure to CAB/LEN is RPV resistance mutations at baseline. OR (95% CI)   40.36 (40 fold greater odd of failure). https://journals.lww.com/aidsonline/fulltext/2021/07150/exploring_predictors_of_hiv_1_virologic_failure_to.1.aspx

     



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    Moskos Tsakiris
    Kingsville MD
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