The caveat to the CDC AI Initial ARV Regimens states I have to have "the results of HIV genotypic resistance testing for reverse transcriptase" before starting Dovato on a naïve patient (and I'm assuming also before switching to Cabenuva LAI from any other ARV).  Is that true?  Also, after I've done that work (including making sure the patient is immune to HBV) can I assume no higher suppression failure rate with the two drug regimens?  


------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

So if you're on Bik, you can develop  resistance due to Bik has FTC which can make an M184V NRTI resistance.  This doesn't affect Bik patients because Bik has TAF, which (I think) continues to suppress despite the resistance like TDF would.  Then if we switch the patients to Dovato (or I'm thinking the same issue for Cabenuva LAI), the TAF is not given and for some perhaps small percentage they loose their suppression and become detectable.   This is stated in the guidelines since it in so many (unclear) words it says Dovato is contraindicated if you haven't done a genotype and ruled out M184V.  So I'm informing my patients who consider switching that there is a perhaps small risk that they will develop resistance if they switch from Bik to Cabenuva or Dovato, and that I will only do that if they have shown side effects or are at risk from TAF.  I'm trying to get a handle on how big the risk of M184V is.  Is there data somewhere?  Anyone else dealing with this?

------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

Original Message:
Sent: 06-05-2021 20:23
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

The caveat to the CDC AI Initial ARV Regimens states I have to have "the results of HIV genotypic resistance testing for reverse transcriptase" before starting Dovato on a naïve patient (and I'm assuming also before switching to Cabenuva LAI from any other ARV).  Is that true?  Also, after I've done that work (including making sure the patient is immune to HBV) can I assume no higher suppression failure rate with the two drug regimens?  


------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

This is a reason why genotyping all naïve patients is needed.   Once they are suppressed, they can't be genotyped and their M184V status can't be determined.  Even a naïve patient may have been infected with M184V genotype.

------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

Original Message:
Sent: 06-11-2021 01:00
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

So if you're on Bik, you can develop  resistance due to Bik has FTC which can make an M184V NRTI resistance.  This doesn't affect Bik patients because Bik has TAF, which continues to suppress despite the resistance.  Then if we switch the patients to Dovato (or I'm thinking the same issue for Cabenuva LAI), the TAF is not given and for some perhaps small percentage they loose their suppression and become detectable.   This is stated in the guidelines since it in so many (unclear) words it says Dovato is contraindicated if you haven't done a genotype and ruled out M184V.  So I'm informing my patients who consider switching that there is a perhaps small risk that they will develop resistance if they switch from Bik to Cabenuva or Dovato, and that I will only do that if they have shown side effects or are at risk from TAF.  I'm trying to get a handle on how big the risk of M184V is.  Is there data somewhere?  Anyone else dealing with this?

------------------------------
Samuel Samalin
Los Angeles CA

Original Message:
Sent: 06-05-2021 20:23
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

The caveat to the CDC AI Initial ARV Regimens states I have to have "the results of HIV genotypic resistance testing for reverse transcriptase" before starting Dovato on a naïve patient (and I'm assuming also before switching to Cabenuva LAI from any other ARV).  Is that true?  Also, after I've done that work (including making sure the patient is immune to HBV) can I assume no higher suppression failure rate with the two drug regimens?  


------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

This is the only M184V study I found:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016422/

It found that lamivudine prevents loss of suppression from M184V, but would still allow blips.

or this:
Dolutegravir response in antiretroviral therapy naïve and experienced patients with M184V/I: Impact in low-and middle-income settings

Sciencedirect		remove preview
Dolutegravir response in antiretroviral therapy naïve and experienced patients with M184V/I: Impact in low-and middle-income settings There is rare emergence of resistance in ART naïve patients on DTG-based regimens. * Simplified 2 NRTI+ DTG or 3TC+DTG regimens commonly retain potency in virologically suppressed patients with M184V/I. * Highly prevalent M184V/I mutation will likely not affect DTG treatment outcomes in Low- and Middle-Income countries. View this on Sciencedirect >

------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

Original Message:
Sent: 06-11-2021 01:15
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

This is a reason why genotyping all naïve patients is needed.   Once they are suppressed, they can't be genotyped and their M184V status can't be determined.  Even a naïve patient may have been infected with M184V genotype.

------------------------------
Samuel Samalin
Los Angeles CA

Original Message:
Sent: 06-11-2021 01:00
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

So if you're on Bik, you can develop  resistance due to Bik has FTC which can make an M184V NRTI resistance.  This doesn't affect Bik patients because Bik has TAF, which continues to suppress despite the resistance.  Then if we switch the patients to Dovato (or I'm thinking the same issue for Cabenuva LAI), the TAF is not given and for some perhaps small percentage they loose their suppression and become detectable.   This is stated in the guidelines since it in so many (unclear) words it says Dovato is contraindicated if you haven't done a genotype and ruled out M184V.  So I'm informing my patients who consider switching that there is a perhaps small risk that they will develop resistance if they switch from Bik to Cabenuva or Dovato, and that I will only do that if they have shown side effects or are at risk from TAF.  I'm trying to get a handle on how big the risk of M184V is.  Is there data somewhere?  Anyone else dealing with this?

------------------------------
Samuel Samalin
Los Angeles CA

Original Message:
Sent: 06-05-2021 20:23
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

The caveat to the CDC AI Initial ARV Regimens states I have to have "the results of HIV genotypic resistance testing for reverse transcriptase" before starting Dovato on a naïve patient (and I'm assuming also before switching to Cabenuva LAI from any other ARV).  Is that true?  Also, after I've done that work (including making sure the patient is immune to HBV) can I assume no higher suppression failure rate with the two drug regimens?  


------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

Hi Samuel,
I found this study in the Journal of Antimicrobial Chemotherapy
https://academic.oup.com/jac/article/74/12/3555/5552319


I hope this helps,
HD

------------------------------
Henry Delu
Los Angeles CA
------------------------------

Original Message:
Sent: 06-11-2021 01:00
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

So if you're on Bik, you can develop  resistance due to Bik has FTC which can make an M184V NRTI resistance.  This doesn't affect Bik patients because Bik has TAF, which (I think) continues to suppress despite the resistance like TDF would.  Then if we switch the patients to Dovato (or I'm thinking the same issue for Cabenuva LAI), the TAF is not given and for some perhaps small percentage they loose their suppression and become detectable.   This is stated in the guidelines since it in so many (unclear) words it says Dovato is contraindicated if you haven't done a genotype and ruled out M184V.  So I'm informing my patients who consider switching that there is a perhaps small risk that they will develop resistance if they switch from Bik to Cabenuva or Dovato, and that I will only do that if they have shown side effects or are at risk from TAF.  I'm trying to get a handle on how big the risk of M184V is.  Is there data somewhere?  Anyone else dealing with this?

------------------------------
Samuel Samalin
Los Angeles CA

Original Message:
Sent: 06-05-2021 20:23
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

The caveat to the CDC AI Initial ARV Regimens states I have to have "the results of HIV genotypic resistance testing for reverse transcriptase" before starting Dovato on a naïve patient (and I'm assuming also before switching to Cabenuva LAI from any other ARV).  Is that true?  Also, after I've done that work (including making sure the patient is immune to HBV) can I assume no higher suppression failure rate with the two drug regimens?  


------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

Hi Samuel,
I read the package insert and it states Dovato is only indicated for use in patients with no history of treatment failure/virologic failure, treatment naive, and virologically suppressed at HIV-1 RNA less than 50 copies/ml. 

DOVATO, a two-drug combination of dolutegravir (integrase strand transfer inhibitor [INSTI]) and lamivudine (nucleoside analogue reverse transcriptase
inhibitor [NRTI]) is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults with no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and  no known substitutions associated with resistance to the individual components of DOVATO. (1)

2.1 Testing Prior to or When Initiating Treatment with DOVATO
1. Test for HBV, due to potential Emergence of Lamivudine-Resistant HBV
2. Test for Pregnancy, due to risk of Neural Tube Defect. There is an increased risk of neural tube defects when dolutegravir, a component of DOVATO, is administered at the time of conception up until the first 6 weeks of gestation.


------------------------------
Henry Delu
Los Angeles CA
------------------------------

Original Message:
Sent: 06-05-2021 20:23
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

The caveat to the CDC AI Initial ARV Regimens states I have to have "the results of HIV genotypic resistance testing for reverse transcriptase" before starting Dovato on a naïve patient (and I'm assuming also before switching to Cabenuva LAI from any other ARV).  Is that true?  Also, after I've done that work (including making sure the patient is immune to HBV) can I assume no higher suppression failure rate with the two drug regimens?  


------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

Original Message:
Sent: 6/16/2021 7:50:00 PM
From: Henry Delu
Subject: RE: Dovato and Cabenuva LAI initial genotype testing requirement?

Hi Samuel,
I read the package insert and it states Dovato is only indicated for use in patients with no history of treatment failure/virologic failure, treatment naive, and virologically suppressed at HIV-1 RNA less than 50 copies/ml. 

DOVATO, a two-drug combination of dolutegravir (integrase strand transfer inhibitor [INSTI]) and lamivudine (nucleoside analogue reverse transcriptase
inhibitor [NRTI]) is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults with no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and  no known substitutions associated with resistance to the individual components of DOVATO. (1)

2.1 Testing Prior to or When Initiating Treatment with DOVATO
1. Test for HBV, due to potential Emergence of Lamivudine-Resistant HBV
2. Test for Pregnancy, due to risk of Neural Tube Defect. There is an increased risk of neural tube defects when dolutegravir, a component of DOVATO, is administered at the time of conception up until the first 6 weeks of gestation.


------------------------------
Henry Delu
Los Angeles CA
------------------------------

Original Message:
Sent: 06-05-2021 20:23
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

The caveat to the CDC AI Initial ARV Regimens states I have to have "the results of HIV genotypic resistance testing for reverse transcriptase" before starting Dovato on a naïve patient (and I'm assuming also before switching to Cabenuva LAI from any other ARV).  Is that true?  Also, after I've done that work (including making sure the patient is immune to HBV) can I assume no higher suppression failure rate with the two drug regimens?  


------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

Typo:  NIH Guideline not NID

------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

Original Message:
Sent: 06-16-2021 21:35
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

Thanks for your reply.  However, it does not address my concern.  I am concerned that the NID Guideline:

"Dolutegravir/lamivudine (AI)-except for individuals with HIV RNA >500,000 copies/mL, HBV coinfection, or when ART is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or HBV testing are available."

states that naive patients that haven't been genotyped are contraindicated for Dovato.   This little fine print item raises about 1000 questions.  I don't feel ready to give Dovato (or Cabenuva) to anyone except

genotypically proven non resistant infected patients.

Sent from Outlook

Original Message:
Sent: 6/16/2021 7:50:00 PM
From: Henry Delu
Subject: RE: Dovato and Cabenuva LAI initial genotype testing requirement?

Hi Samuel,
I read the package insert and it states Dovato is only indicated for use in patients with no history of treatment failure/virologic failure, treatment naive, and virologically suppressed at HIV-1 RNA less than 50 copies/ml. 

DOVATO, a two-drug combination of dolutegravir (integrase strand transfer inhibitor [INSTI]) and lamivudine (nucleoside analogue reverse transcriptase
inhibitor [NRTI]) is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults with no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and  no known substitutions associated with resistance to the individual components of DOVATO. (1)

2.1 Testing Prior to or When Initiating Treatment with DOVATO
1. Test for HBV, due to potential Emergence of Lamivudine-Resistant HBV
2. Test for Pregnancy, due to risk of Neural Tube Defect. There is an increased risk of neural tube defects when dolutegravir, a component of DOVATO, is administered at the time of conception up until the first 6 weeks of gestation.


------------------------------
Henry Delu
Los Angeles CA

Original Message:
Sent: 06-05-2021 20:23
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

The caveat to the CDC AI Initial ARV Regimens states I have to have "the results of HIV genotypic resistance testing for reverse transcriptase" before starting Dovato on a naïve patient (and I'm assuming also before switching to Cabenuva LAI from any other ARV).  Is that true?  Also, after I've done that work (including making sure the patient is immune to HBV) can I assume no higher suppression failure rate with the two drug regimens?  


------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

Hi Samuel,
I agree that the new update requires the results of HIV genotypic resistance testing for reverse transcriptase before starting Dovota (as well as exclusion from Dovato if HIV RNA is over 500,000 copies/ml, HBV coinfection or unknown HBV status). Based upon the update provided below, I would recommend starting the patient on Biktarvy, as this is also a preferred initial regimen, single pill, and does not have the same restrictions as Dovato.
Thanks,
HD

https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/what-start-initial-combination-regimens-antiretroviral-naive

The Panel on Antiretroviral Guidelines for Adults and Adolescents (the Panel) classifies the following regimens as Recommended Initial Regimens for Most People with HIV (in alphabetical order):

• Bictegravir/tenofovir alafenamide/emtricitabine (AI)^a
• Dolutegravir/abacavir/lamivudine-only for individuals who are HLA-B*5701 negative and without chronic hepatitis B virus (HBV) coinfection (AI)
• Dolutegravir plus (emtricitabine or lamivudine) plus (tenofovir alafenamide [TAF] or tenofovir disoproxil fumarate [TDF])^b (AI)
• Dolutegravir/lamivudine (AI)-except for individuals with HIV RNA >500,000 copies/mL, HBV coinfection, or when ART is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or HBV testing are available.

------------------------------
Henry Delu
Los Angeles CA
------------------------------

Original Message:
Sent: 06-16-2021 21:35
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

Thanks for your reply.  However, it does not address my concern.  I am concerned that the NID Guideline:

"Dolutegravir/lamivudine (AI)-except for individuals with HIV RNA >500,000 copies/mL, HBV coinfection, or when ART is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or HBV testing are available."

states that naive patients that haven't been genotyped are contraindicated for Dovato.   This little fine print item raises about 1000 questions.  I don't feel ready to give Dovato (or Cabenuva) to anyone except

genotypically proven non resistant infected patients.

Sent from Outlook

Original Message:
Sent: 6/16/2021 7:50:00 PM
From: Henry Delu
Subject: RE: Dovato and Cabenuva LAI initial genotype testing requirement?

Hi Samuel,
I read the package insert and it states Dovato is only indicated for use in patients with no history of treatment failure/virologic failure, treatment naive, and virologically suppressed at HIV-1 RNA less than 50 copies/ml. 

DOVATO, a two-drug combination of dolutegravir (integrase strand transfer inhibitor [INSTI]) and lamivudine (nucleoside analogue reverse transcriptase
inhibitor [NRTI]) is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults with no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and  no known substitutions associated with resistance to the individual components of DOVATO. (1)

2.1 Testing Prior to or When Initiating Treatment with DOVATO
1. Test for HBV, due to potential Emergence of Lamivudine-Resistant HBV
2. Test for Pregnancy, due to risk of Neural Tube Defect. There is an increased risk of neural tube defects when dolutegravir, a component of DOVATO, is administered at the time of conception up until the first 6 weeks of gestation.


------------------------------
Henry Delu
Los Angeles CA

Original Message:
Sent: 06-05-2021 20:23
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

The caveat to the CDC AI Initial ARV Regimens states I have to have "the results of HIV genotypic resistance testing for reverse transcriptase" before starting Dovato on a naïve patient (and I'm assuming also before switching to Cabenuva LAI from any other ARV).  Is that true?  Also, after I've done that work (including making sure the patient is immune to HBV) can I assume no higher suppression failure rate with the two drug regimens?  


------------------------------
Samuel Samalin
Los Angeles CA
------------------------------

Hi Samuel,

I keep patient's on a 3-active medication regimen vs. two-active especially if they are suppressed <50 copies and a genotype would normal not be reflexed off the RNA.  I may order a genotype archive/proviral DNA in supressed patients to look for archived resistance mutations if the patient really wants to switch from Biktarvy to Dovato. Most patients stay on Biktarvy from my experience. I do understand the concern with continued suppression of M184V/I if you remove the TAF since the boosted TXF effect (from M184V/I) wouldn't be present, in theory you could eventually have inferior suppression of the mutation and end up with resistance. This is a less likely scenario, but possible. Like you, I would not start Dovato w/o genotype results. Even with those results, I would use caution switching a patient from an active 3-drug regimen to a 2-drug regimen. 

------------------------------
Martel S. Warden, MHA, MSN, APRN
Family Nurse Practitioner
Christian Community Health Center
Chicago, IL 60628
------------------------------

Original Message:
Sent: 06-16-2021 21:35
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

Thanks for your reply.  However, it does not address my concern.  I am concerned that the NID Guideline:

"Dolutegravir/lamivudine (AI)-except for individuals with HIV RNA >500,000 copies/mL, HBV coinfection, or when ART is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or HBV testing are available."

states that naive patients that haven't been genotyped are contraindicated for Dovato.   This little fine print item raises about 1000 questions.  I don't feel ready to give Dovato (or Cabenuva) to anyone except

genotypically proven non resistant infected patients.

Sent from Outlook

Original Message:
Sent: 6/16/2021 7:50:00 PM
From: Henry Delu
Subject: RE: Dovato and Cabenuva LAI initial genotype testing requirement?

Hi Samuel,
I read the package insert and it states Dovato is only indicated for use in patients with no history of treatment failure/virologic failure, treatment naive, and virologically suppressed at HIV-1 RNA less than 50 copies/ml. 

DOVATO, a two-drug combination of dolutegravir (integrase strand transfer inhibitor [INSTI]) and lamivudine (nucleoside analogue reverse transcriptase
inhibitor [NRTI]) is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults with no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and  no known substitutions associated with resistance to the individual components of DOVATO. (1)

2.1 Testing Prior to or When Initiating Treatment with DOVATO
1. Test for HBV, due to potential Emergence of Lamivudine-Resistant HBV
2. Test for Pregnancy, due to risk of Neural Tube Defect. There is an increased risk of neural tube defects when dolutegravir, a component of DOVATO, is administered at the time of conception up until the first 6 weeks of gestation.


------------------------------
Henry Delu
Los Angeles CA

Original Message:
Sent: 06-05-2021 20:23
From: Samuel Samalin
Subject: Dovato and Cabenuva LAI initial genotype testing requirement?

The caveat to the CDC AI Initial ARV Regimens states I have to have "the results of HIV genotypic resistance testing for reverse transcriptase" before starting Dovato on a naïve patient (and I'm assuming also before switching to Cabenuva LAI from any other ARV).  Is that true?  Also, after I've done that work (including making sure the patient is immune to HBV) can I assume no higher suppression failure rate with the two drug regimens?  


------------------------------
Samuel Samalin
Los Angeles CA
------------------------------