Academy Exchange

38 y/o male with HIV, hx of uncontrolled HTN, controlled migraine, vitamin B12 and folate deficiency, hyperthyroidism who has been having fluctuating VL with inconsistent adherence.

On 5/2024 visit, Odefsey was changed to Biktarvy as VL increased to 5600 from 409 (12/2023) from 57 (1/2023).  

GS resistance obtained from 5/2024 visit noted for K65R, E138A, K103N, Y188H  

All previous GT on file noted for:
    RT: V118I
    PI: L10V, M63I, D60E, I92V
    II: I203M

ARV hx:  Initially started on Atripla and changed to Odefsey in 2017.  Started Biktarvy 5/2024.  The K65R mutation results in some level of resistance across the NRTI class. I've considered starting pt on DTG and Prezcobix (pt is negative for hepB) for at least 2 fully active drugs but decided to see if Biktarvy can suppress him to minimize pill burden because I recalled studies done that showed pts suppressed on Truvada and DTG with NRTI resistance (either Visend or Nadia??).  Please correct me if I'm wrong.

Labs were done s/p ARV change to Biktarvy but unfortunately the sample was mishandled and I haven't been able to get updated labs until this week, hopefully.

Question:

Is the Prezcobix+DTG better for the patient in this case, rather than Biktarvy, as he doesn't have at least 2 fully suppressive meds on Biktarvy?

I'm concerned about integrase resistance in this patient.

I've attached his recent resistance test.  Should the other mutations noted at the end of the report be included in the Stanford HIV database when inputting resistance?

I would appreciate any thoughts or recommendations.

Thank you.

Jenny,

The relevant mutation here is K65R, which as you know causes some loss of susceptibility to TAF and TDF.  Interestingly, you did not pick up M184V, which suggests poor recent adherence.  It's unlikely that he would have failed Odefsey without M184 as well as NNRTI mutations, so the absence of this mutation on genotype suggests that he hadn't been taking enough doses to maintain selective pressure.  If we assume he also has M184V, that increases tenofovir susceptibility somewhat.

Although it's an off-label use, there is growing evidence that Biktarvy can work in the presence of significant NRTI mutations, including the K65R/M184V combination. Originally these data came from Gilead studies in virologically suppressed individuals, but more recent studies in people failing first-line NNRTI-based therapy (with documented or presumed NRTI resistance) have demonstrated good outcomes with switches to DTG + either 3TC/TDF or FTC/TAF (VISEND, NADIA, D2EFT) or Bikarvy (GHESKIO). Given this patient's poor adherence, the use of a high barrier, simple, well tolerated regimen may be critically important.  I don't think you'd be wrong to keep him on Biktarvy and follow him closely. 

This case also points out that Odefsey has important food requirements and a low resistance barrier, so it's appropriate only for highly adherent patients.

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Joel Gallant, MD, MPH
Santa Fe, NM
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