Academy Exchange

Hello, 

I have a patient who has been virally suppressed on Truvada (FTC/TDF), Intelence (ETR) & Isentress (RAL) and looking to simplify regimen. Patient came to me on this regimen, attempted to get records from previous provider but had difficulty getting these to determine why this is patient's regimen. Unable to get updated resistance testing due to viral suppressed status. I did receive records from prior resistance testing which does show reduced susceptibility to several NRTIs, NNRTIs and PIs, however these are from >20 years ago and no record of integrase susceptibility testing. Was looking to consider changing to single tablet regimen to minimize medications patient is taking if able. Thoughts on next steps? Looking to switch to Biktarvy for single tablet regimen with high barrier to resistance however the prior phenosense results (as referenced above) are throwing me off, just want to make sure I am not missing anything. Any advice is appreciated. 

Thank you, 

Ryan

------------------------------
Ryan K. Doyle, DO (he/him/his)
rymed89@gmail.com
Grand Rapids, MI
------------------------------

Ryan,

You could get a proviral DNA genotype (PhenoSense Archive). This test can be helpful when it shows mutations, though it's less helpful when it doesn't. 

At first glance, the easiest simplification switch would be to Biktarvy + Intelence, which would reduce pill burden. However, there may be a modest reduction of bictegravir levels with this combination, which has not been studied clinically. (That same interaction applies to the combination of Isentress + Intelence, which he's on now, though there's more clinical data there.)  My guess is that it's not a clinically significant interaction in either case, but it's still not recommended.

As for Biktarvy alone, if he has no INSTI resistance then the only relevant resistance would be NRTI resistance. There are multiple studies showing that people who are virologically suppressed do fine on Biktarvy despite NRTI resistance, as long as the bictegravir component is fully active.  However, that's an off-label use of Biktarvy, and potentially risky if there's a chance of INSTI resistance.

Another approach would be Biktarvy + Sulenca (lenacapavir), a single-tablet regimen plus an every 6 month injection. The ARTISTRY trials are also looking at bictegravir/lenacapavir as a single-table daily oral regimen in people without INSTI resistance.  So far, the results look promising, but this isn't available yet.

Hello, 

I have a patient who has been virally suppressed on Truvada (FTC/TDF), Intelence (ETR) & Isentress (RAL) and looking to simplify regimen. Patient came to me on this regimen, attempted to get records from previous provider but had difficulty getting these to determine why this is patient's regimen. Unable to get updated resistance testing due to viral suppressed status. I did receive records from prior resistance testing which does show reduced susceptibility to several NRTIs, NNRTIs and PIs, however these are from >20 years ago and no record of integrase susceptibility testing. Was looking to consider changing to single tablet regimen to minimize medications patient is taking if able. Thoughts on next steps? Looking to switch to Biktarvy for single tablet regimen with high barrier to resistance however the prior phenosense results (as referenced above) are throwing me off, just want to make sure I am not missing anything. Any advice is appreciated. 

Thank you, 

Ryan

------------------------------
Ryan K. Doyle, DO (he/him/his)
rymed89@gmail.com
Grand Rapids, MI
------------------------------

Joel, 

Thank you for the advice. I finally (much delayed) got an archive genotype for the patient above I inquired about. Mutations of M41M, V245K, L74I (integrase). Report showing only resistance possible with zidovudine. Using HIV-ASSIST, it does seem Biktarvy alone could be a reasonable option. Thoughts? 

Ryan

Ryan,

You could get a proviral DNA genotype (PhenoSense Archive). This test can be helpful when it shows mutations, though it's less helpful when it doesn't. 

At first glance, the easiest simplification switch would be to Biktarvy + Intelence, which would reduce pill burden. However, there may be a modest reduction of bictegravir levels with this combination, which has not been studied clinically. (That same interaction applies to the combination of Isentress + Intelence, which he's on now, though there's more clinical data there.)  My guess is that it's not a clinically significant interaction in either case, but it's still not recommended.

As for Biktarvy alone, if he has no INSTI resistance then the only relevant resistance would be NRTI resistance. There are multiple studies showing that people who are virologically suppressed do fine on Biktarvy despite NRTI resistance, as long as the bictegravir component is fully active.  However, that's an off-label use of Biktarvy, and potentially risky if there's a chance of INSTI resistance.

Another approach would be Biktarvy + Sulenca (lenacapavir), a single-tablet regimen plus an every 6 month injection. The ARTISTRY trials are also looking at bictegravir/lenacapavir as a single-table daily oral regimen in people without INSTI resistance.  So far, the results look promising, but this isn't available yet.

Hello, 

I have a patient who has been virally suppressed on Truvada (FTC/TDF), Intelence (ETR) & Isentress (RAL) and looking to simplify regimen. Patient came to me on this regimen, attempted to get records from previous provider but had difficulty getting these to determine why this is patient's regimen. Unable to get updated resistance testing due to viral suppressed status. I did receive records from prior resistance testing which does show reduced susceptibility to several NRTIs, NNRTIs and PIs, however these are from >20 years ago and no record of integrase susceptibility testing. Was looking to consider changing to single tablet regimen to minimize medications patient is taking if able. Thoughts on next steps? Looking to switch to Biktarvy for single tablet regimen with high barrier to resistance however the prior phenosense results (as referenced above) are throwing me off, just want to make sure I am not missing anything. Any advice is appreciated. 

Thank you, 

Ryan

------------------------------
Ryan K. Doyle, DO (he/him/his)
rymed89@gmail.com
Grand Rapids, MI
------------------------------

I assume you mean M41L.  (M41M would be wild type, not a mutation).

You're right that based on the proviral DNA genotype alone, Biktarvy should work well.  That being said, it's failing to pick up mutations that were detected in the past, because you said that he previously had more significant resistance on previous testing that doesn't show up now.  As a result, I'm not sure the current archive genotype helps you very much in this situation, though the lack of detectable INSTI resistance is at least reassuring.

Gilead has done a number of studies in suppressed patients who switched to Biktarvy, and it did well at maintaining suppression despite the presence of NRTI mutations, including M184V, TAMs, and/or K65R. (In such cases, the presence of NNRTI or PI resistance should be irrelevant). Based on those studies, your patient should do fine with an off-label switch to Biktarvy, though I would follow him closely in the beginning. These study results can't be extrapolated to non-suppressed patients, where we have a lot less data. 

Joel, 

Thank you for the advice. I finally (much delayed) got an archive genotype for the patient above I inquired about. Mutations of M41M, V245K, L74I (integrase). Report showing only resistance possible with zidovudine. Using HIV-ASSIST, it does seem Biktarvy alone could be a reasonable option. Thoughts? 

Ryan

Ryan,

You could get a proviral DNA genotype (PhenoSense Archive). This test can be helpful when it shows mutations, though it's less helpful when it doesn't. 

At first glance, the easiest simplification switch would be to Biktarvy + Intelence, which would reduce pill burden. However, there may be a modest reduction of bictegravir levels with this combination, which has not been studied clinically. (That same interaction applies to the combination of Isentress + Intelence, which he's on now, though there's more clinical data there.)  My guess is that it's not a clinically significant interaction in either case, but it's still not recommended.

As for Biktarvy alone, if he has no INSTI resistance then the only relevant resistance would be NRTI resistance. There are multiple studies showing that people who are virologically suppressed do fine on Biktarvy despite NRTI resistance, as long as the bictegravir component is fully active.  However, that's an off-label use of Biktarvy, and potentially risky if there's a chance of INSTI resistance.

Another approach would be Biktarvy + Sulenca (lenacapavir), a single-tablet regimen plus an every 6 month injection. The ARTISTRY trials are also looking at bictegravir/lenacapavir as a single-table daily oral regimen in people without INSTI resistance.  So far, the results look promising, but this isn't available yet.

Hello, 

I have a patient who has been virally suppressed on Truvada (FTC/TDF), Intelence (ETR) & Isentress (RAL) and looking to simplify regimen. Patient came to me on this regimen, attempted to get records from previous provider but had difficulty getting these to determine why this is patient's regimen. Unable to get updated resistance testing due to viral suppressed status. I did receive records from prior resistance testing which does show reduced susceptibility to several NRTIs, NNRTIs and PIs, however these are from >20 years ago and no record of integrase susceptibility testing. Was looking to consider changing to single tablet regimen to minimize medications patient is taking if able. Thoughts on next steps? Looking to switch to Biktarvy for single tablet regimen with high barrier to resistance however the prior phenosense results (as referenced above) are throwing me off, just want to make sure I am not missing anything. Any advice is appreciated. 

Thank you, 

Ryan

------------------------------
Ryan K. Doyle, DO (he/him/his)
rymed89@gmail.com
Grand Rapids, MI
------------------------------

Hello, 

I have a patient who has been virally suppressed on Truvada (FTC/TDF), Intelence (ETR) & Isentress (RAL) and looking to simplify regimen. Patient came to me on this regimen, attempted to get records from previous provider but had difficulty getting these to determine why this is patient's regimen. Unable to get updated resistance testing due to viral suppressed status. I did receive records from prior resistance testing which does show reduced susceptibility to several NRTIs, NNRTIs and PIs, however these are from >20 years ago and no record of integrase susceptibility testing. Was looking to consider changing to single tablet regimen to minimize medications patient is taking if able. Thoughts on next steps? Looking to switch to Biktarvy for single tablet regimen with high barrier to resistance however the prior phenosense results (as referenced above) are throwing me off, just want to make sure I am not missing anything. Any advice is appreciated. 

Thank you, 

Ryan

------------------------------
Ryan K. Doyle, DO (he/him/his)
rymed89@gmail.com
Grand Rapids, MI
------------------------------

Given that Intelence wasn't approved until 2007 and they may have had little exposure to F/TDF within the window of approval and the test result, that very old assay may no longer be relevant anyway. I would try getting an archived genotype. At the very least there should be little to no risk in simplifying to Biktarvy and Intelence while you await results. You can simplify further if you have at least 2 fully active agents in Biktarvy. If he happens to have a K65R mutation without M184V, I would simplify to Dovato, even though Biktarvy would likely offer the same protection.

Hello, 

I have a patient who has been virally suppressed on Truvada (FTC/TDF), Intelence (ETR) & Isentress (RAL) and looking to simplify regimen. Patient came to me on this regimen, attempted to get records from previous provider but had difficulty getting these to determine why this is patient's regimen. Unable to get updated resistance testing due to viral suppressed status. I did receive records from prior resistance testing which does show reduced susceptibility to several NRTIs, NNRTIs and PIs, however these are from >20 years ago and no record of integrase susceptibility testing. Was looking to consider changing to single tablet regimen to minimize medications patient is taking if able. Thoughts on next steps? Looking to switch to Biktarvy for single tablet regimen with high barrier to resistance however the prior phenosense results (as referenced above) are throwing me off, just want to make sure I am not missing anything. Any advice is appreciated. 

Thank you, 

Ryan

------------------------------
Ryan K. Doyle, DO (he/him/his)
rymed89@gmail.com
Grand Rapids, MI
------------------------------

Hello, 

I have a patient who has been virally suppressed on Truvada (FTC/TDF), Intelence (ETR) & Isentress (RAL) and looking to simplify regimen. Patient came to me on this regimen, attempted to get records from previous provider but had difficulty getting these to determine why this is patient's regimen. Unable to get updated resistance testing due to viral suppressed status. I did receive records from prior resistance testing which does show reduced susceptibility to several NRTIs, NNRTIs and PIs, however these are from >20 years ago and no record of integrase susceptibility testing. Was looking to consider changing to single tablet regimen to minimize medications patient is taking if able. Thoughts on next steps? Looking to switch to Biktarvy for single tablet regimen with high barrier to resistance however the prior phenosense results (as referenced above) are throwing me off, just want to make sure I am not missing anything. Any advice is appreciated. 

Thank you, 

Ryan

------------------------------
Ryan K. Doyle, DO (he/him/his)
rymed89@gmail.com
Grand Rapids, MI
------------------------------