Academy Exchange

 View Only
  • 1.  A unique case of drug resistance

    Posted 05-15-2022 02:46
    Edited by Alok Vashishtha 05-15-2022 03:06

    Dear All.

    I am Dr Alok Vashishtha from Haridwar, India.

    A 24 year old boy case history was received by us for opinion on 10th April 2022. This boy is on ART from 04th January, 2006. The treatment history is provided in table below. As his HIV-1 Drug Resistance Testing was never done before, so we got it done and it showed resistance to no drugs. Genotype Resistance Test report attached in two parts for reference. We thought it as the case of non-adherence and with detailed enquiry patient told us that he was taking Darunavir 600 mg + Ritonavir 100 mg only once daily. So we made it now to twice daily and will repeat HIV RNA Quantitative RT-PCR after 6 weeks. My concern is why Genotype resistance testing is showing all drugs susceptible. Just to add that we got Genotype resistance testing repeated at another lab and it showed same pattern.

    Looking forward your valuable opinion for our patient.

     Treatment history of patient:

    DD-MM-YYYY

    Absolute

    CD4 counts

    HIV RNA QUANTITATIVE RT-PCR (Copies/ml)

    MEDICATIONS

    04-07-2006

    173

    ND

    D4T, 3TC, NVP

    01-09-2007

    775

    ND

    AZT, 3TC, NVP

    01-07-2008

    788

    ND

    AZT, 3TC, NVP

    08-10-2009

    941

    ND

    AZT, 3TC, NVP

    27-09-2010

    996

    ND

    AZT, 3TC, NVP

    06-01-2012

    1123

    ND

    AZT, 3TC, NVP

    13-09-2013

    946

    ND

    AZT, 3TC, NVP

    08-11-2014

    759

    ND

    AZT, 3TC, NVP

    09-11-2015

    675

    ND

    AZT, 3TC, NVP

    10-05-2016

    471

    ND

    AZT, 3TC. NVP

    24-03-2017

    504

    18387

    ATV/r, TDF, STC

    25-09-2017

    375

    ND

    ATV/r, TDF, 3TC

    09-12-2018

    379

    ND

    ATV/r, TDF, 3TC

    28-10-2018

    NA

    128

    ATV/r, TDF, 3TC

    27-03-2019

    432

    ND

    ATV/r, TDF, 3TC

    16-10-2019

    226

    43721

    ATV/r, TDF, 3TC

    24-02-2020

    207

    ND

    ATV/r, TDF, 3TC

    13-01-2021

    165

    97730

    DRV/r, DTG (12 hourly)

    13-12-2021

    128

    84503

    DRV/r, DTG (12 hourly)

     

    With best regards

    Dr Alok Vashishtha

    MBBS, MDHM, FIHM, AAHIVS

    Centre for Infectious Diseases,

    Haridwar, India

    Attachment(s)

    docx
    GBL PART 2.docx   83 KB 1 version
    docx
    GBL PART 1.docx   136 KB 1 version


  • 2.  RE: A unique case of drug resistance

    Posted 05-16-2022 11:45
    Hi Alok,

    Unfortunately, if the resistance tests show wild type virus, there could be no other explanation other than he is currently not taking his ARV drugs.  So let me be clear.    He certainly could have minority variants with resistance mutations.   But these  variants will be overwhelmed by the wild type virus population.  So, I would recommend starting a regimen that you think should work (as you are doing), and then repeating a resistance test IF he continues to be viremic, AND you are sure that he is taking his meds.   Obviously, the main issue is to get to the source of his non compliance, and try to resolve that. If he continues to not take his meds, he will have continued viremia and wild type will show on resistance testing.   Hope that helps!

    ------------------------------
    Adam Zweig
    AIDS Healthcare Foundation
    San Diego CA
    ------------------------------



  • 3.  RE: A unique case of drug resistance

    Posted 05-20-2022 15:17
    Hi Alok!

    I agree with Adam, that most likely the patient does not have enough drug in their system to develop resistance. so something is very telling to me on the labs you show. it looks like they were not detected for a very long time, then viral load shot up to 18387, then back to undetectable then a few times pretty high. so it appears the patient's viral set point is in the 10s of thousands. this is normal when someoen comes off meds totally. when someone has resistance, basically all of the virus that CAN be killed off will be, and there will actually be a much smaller number of virus, sometimes in the thousands. now the longer the person is on a failing regimen and the longer the resistant virus has time, it will then become higher and higher, but that doesnt strike me as what is happening.

    one question I have, is there a reason this patient is on twice daily darunavir and dolutegravir vs once a day? I see they have only been on ATV as a PI and NVP as an NNRTI, and I would not expect to have PI mutations to DRV so you COULD do once daily DRV at 800mg and once daily DTG. unless this patient is also on other medications that have drug interactions causing you to have them on a twice daily regimen. yeah this def seems like someone who is just struggling with adherence and might not want to admit issues. 

    Best 

    Angela

    ------------------------------
    Angela Kapalko
    Physician Assistant Chairperson for AAHIVM
    Philadelphia FIGHT CommunityHealth Centers
    Philadelphia PA
    akapalko@fight.org
    ------------------------------