Topics

NATAP/IAC: Telomerase/Aging & ART Strategies

Jules Levin
 


www.natap.org

Antiretroviral Treatment Maintenance Strategies and Blood Telomere Length Change

 this study published here:

Reported by Jules Levin

22nd International AIDS Conference, Amsterdam, Netherlands, July 23-27, 2018

 

R. Montejano1, N. Stella-Ascariz1, S. Monge1, J.I. Bernardino1, I. Pérez-Valero1, M. Montes1, L. Martín-Carbonero1, J. González-García1, J. Rodriguez-Centeno1, B. Rodes1, B. Alejos2, R. de Miguel1, A. Esteban-Cantos1, R. Perona3, J. Arribas1 

1Hospital La Paz Institute for Health Research, Madrid, Spain, 2Institute of Health Carlos III, Madrid, Spain, 3Institute of Biomed Research Alberto Sols, Madrid, Spain







_______________________________________________
NATAP natapdoctors mailing list 

Nelson Vergel
 

Thanks, Jules. Wow. So the regimen that had Viread showed better recovery of telomere length and the regimen without a nucleoside (Prezista plus Isentress)

Those of you who do not know what telomere length is should read this https://learn.genetics.utah.edu/content/basics/telomeres/


On Aug 8, 2018, at 2:41 PM, Jules Levin via Groups.Io <julev@...> wrote:


www.natap.org

Antiretroviral Treatment Maintenance Strategies and Blood Telomere Length Change

 this study published here:

Reported by Jules Levin

22nd International AIDS Conference, Amsterdam, Netherlands, July 23-27, 2018

 

R. Montejano1, N. Stella-Ascariz1, S. Monge1, J.I. Bernardino1, I. Pérez-Valero1, M. Montes1, L. Martín-Carbonero1, J. González-García1, J. Rodriguez-Centeno1, B. Rodes1, B. Alejos2, R. de Miguel1, A. Esteban-Cantos1, R. Perona3, J. Arribas1 

1Hospital La Paz Institute for Health Research, Madrid, Spain, 2Institute of Health Carlos III, Madrid, Spain, 3Institute of Biomed Research Alberto Sols, Madrid, Spain







_______________________________________________
NATAP natapdoctors mailing list 
<jiy364.pdf>
<jiy364_suppl_supplementary-material.docx>
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Jules Levin
 

No, in the poster at IAC - all regimens showed telomerase improvement on ART - But TDF had the lowest improvement, abacavir was 2nd lowest but almost the same as TDF (see publication, this study was just published & thats what authors say - suggesting more improvement in telomerase may help ameliorate immunosenesencence, so the authors say !! .. Nuke sparing had the nest telomerase improvement, so NO NUKES. Look at pics I inserted below…. I attached both publication pdfs here too.   PS so just for thought: doravirine, the new NNRTI is supposed to NOT have CNS side effects like other NNRTI have, has no effect on lipids. Does it affect mitochondria or telomerase, I don’t know? What about dolutegravir+rilpivirine, nuke sparing but rilpivirine has some CNS side effects not as bad as efavirenz but some, what is affect of dolutegravir on mitochondria or tolemerase, we don’t know? But for some older HIV+ some experience CNS side effects, dolutegravir is potent CNS & brain entry. What is the long term affects of high CNS penetration particularly in older aging HIV+, we don’t know, we know efavirenz can damage the brain maybe more in older aging HIV+.

Then in the other study also just published TDF & DRV regimen did do better: than DRV+RAL
Blood telomere length analysis showed that at baseline there were no statistically significant differences between groups,. After 96 weeks, both groups had a gain in TL: mean TL in the total analyzed samples increased 0.028 (Figure 1 and Table S2). However, increase in TL was only significant in the tenofovir disoproxil fumarate/emtricitabine group. Additionally, the proportion of participants who had increase in TL at follow-up was 71% in tenofovir disoproxil fumarate/emtricitabine group versus 57% in the raltegravir group.
 
We hypothesize that participants receiving darunavir and raltegravir could have persistent HIV replication in lymph nodes - due to lower tissue concentrations- than participants receiving darunavir and tenofovir disoproxil fumarate/emtricitabine. This persistent antigenic stimulation in lymph nodes would maintain the stimulus for T cells to differentiate to mature phenotypes with shorter TL. In naïve participants with high levels of HIV replication a higher penetration of tenofovir disoproxil fumarate/emtricitabine in lymph node tissue may overcome the inhibitory effect of tenofovir upon telomerase10- 









On Aug 8, 2018, at 4:14 PM, "Nelson Vergel" <nelsonvergel@...> wrote:

Thanks, Jules. Wow. So the regimen that had Viread showed better recovery of telomere length and the regimen without a nucleoside (Prezista plus Isentress)

Those of you who do not know what telomere length is should read this https://learn.genetics.utah.edu/content/basics/telomeres/


On Aug 8, 2018, at 2:41 PM, Jules Levin via Groups.Io <julev@...> wrote:


www.natap.org

Antiretroviral Treatment Maintenance Strategies and Blood Telomere Length Change

 this study published here:

Reported by Jules Levin

22nd International AIDS Conference, Amsterdam, Netherlands, July 23-27, 2018

 

R. Montejano1, N. Stella-Ascariz1, S. Monge1, J.I. Bernardino1, I. Pérez-Valero1, M. Montes1, L. Martín-Carbonero1, J. González-García1, J. Rodriguez-Centeno1, B. Rodes1, B. Alejos2, R. de Miguel1, A. Esteban-Cantos1, R. Perona3, J. Arribas1 

1Hospital La Paz Institute for Health Research, Madrid, Spain, 2Institute of Health Carlos III, Madrid, Spain, 3Institute of Biomed Research Alberto Sols, Madrid, Spain







_______________________________________________
NATAP natapdoctors mailing list 
<jiy364.pdf>
<jiy364_suppl_supplementary-material.docx>
<Screen Shot 2018-08-08 at 3.22.04 PM.png>
<Screen Shot 2018-08-08 at 3.11.49 PM.png>
<Screen Shot 2018-08-08 at 3.12.24 PM.png>
<Screen Shot 2018-08-08 at 3.12.48 PM.png>
<Screen Shot 2018-08-08 at 3.13.05 PM.png>
<Screen Shot 2018-08-08 at 3.15.24 PM.png>
<Screen Shot 2018-08-08 at 3.13.41 PM.png>
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larry williams
 

very interesting article.  In plain English, does that mean my Genvoya is good for my telomere length or bad for my telomeres?  I'm 63, undetectable for 6 years.  Thanks.

On Wednesday, August 8, 2018, 3:37:45 PM CDT, Jules Levin via Groups.Io <julev@...> wrote:


No, in the poster at IAC - all regimens showed telomerase improvement on ART - But TDF had the lowest improvement, abacavir was 2nd lowest but almost the same as TDF (see publication, this study was just published & thats what authors say - suggesting more improvement in telomerase may help ameliorate immunosenesencence, so the authors say !! .. Nuke sparing had the nest telomerase improvement, so NO NUKES. Look at pics I inserted below…. I attached both publication pdfs here too.   PS so just for thought: doravirine, the new NNRTI is supposed to NOT have CNS side effects like other NNRTI have, has no effect on lipids. Does it affect mitochondria or telomerase, I don’t know? What about dolutegravir+rilpivirine, nuke sparing but rilpivirine has some CNS side effects not as bad as efavirenz but some, what is affect of dolutegravir on mitochondria or tolemerase, we don’t know? But for some older HIV+ some experience CNS side effects, dolutegravir is potent CNS & brain entry. What is the long term affects of high CNS penetration particularly in older aging HIV+, we don’t know, we know efavirenz can damage the brain maybe more in older aging HIV+.

Then in the other study also just published TDF & DRV regimen did do better: than DRV+RAL
Blood telomere length analysis showed that at baseline there were no statistically significant differences between groups,. After 96 weeks, both groups had a gain in TL: mean TL in the total analyzed samples increased 0.028 (Figure 1 and Table S2). However, increase in TL was only significant in the tenofovir disoproxil fumarate/emtricitabine group. Additionally, the proportion of participants who had increase in TL at follow-up was 71% in tenofovir disoproxil fumarate/emtricitabine group versus 57% in the raltegravir group.
 
We hypothesize that participants receiving darunavir and raltegravir could have persistent HIV replication in lymph nodes - due to lower tissue concentrations- than participants receiving darunavir and tenofovir disoproxil fumarate/emtricitabine. This persistent antigenic stimulation in lymph nodes would maintain the stimulus for T cells to differentiate to mature phenotypes with shorter TL. In naïve participants with high levels of HIV replication a higher penetration of tenofovir disoproxil fumarate/emtricitabine in lymph node tissue may overcome the inhibitory effect of tenofovir upon telomerase10- 









On Aug 8, 2018, at 4:14 PM, "Nelson Vergel" <nelsonvergel@...> wrote:

Thanks, Jules. Wow. So the regimen that had Viread showed better recovery of telomere length and the regimen without a nucleoside (Prezista plus Isentress)

Those of you who do not know what telomere length is should read this https://learn.genetics.utah.edu/content/basics/telomeres/


On Aug 8, 2018, at 2:41 PM, Jules Levin via Groups.Io <julev@...> wrote:


www.natap.org

Antiretroviral Treatment Maintenance Strategies and Blood Telomere Length Change

 this study published here:

Reported by Jules Levin

22nd International AIDS Conference, Amsterdam, Netherlands, July 23-27, 2018

 

R. Montejano1, N. Stella-Ascariz1, S. Monge1, J.I. Bernardino1, I. Pérez-Valero1, M. Montes1, L. Martín-Carbonero1, J. González-García1, J. Rodriguez-Centeno1, B. Rodes1, B. Alejos2, R. de Miguel1, A. Esteban-Cantos1, R. Perona3, J. Arribas1 

1Hospital La Paz Institute for Health Research, Madrid, Spain, 2Institute of Health Carlos III, Madrid, Spain, 3Institute of Biomed Research Alberto Sols, Madrid, Spain







_______________________________________________
NATAP natapdoctors mailing list 
<jiy364.pdf>
<jiy364_suppl_supplementary-material.docx>
<Screen Shot 2018-08-08 at 3.22.04 PM.png>
<Screen Shot 2018-08-08 at 3.11.49 PM.png>
<Screen Shot 2018-08-08 at 3.12.24 PM.png>
<Screen Shot 2018-08-08 at 3.12.48 PM.png>
<Screen Shot 2018-08-08 at 3.13.05 PM.png>
<Screen Shot 2018-08-08 at 3.15.24 PM.png>
<Screen Shot 2018-08-08 at 3.13.41 PM.png>
<Screen Shot 2018-08-08 at 3.14.34 PM.png>
<Screen Shot 2018-08-08 at 3.16.27 PM.png>
<Screen Shot 2018-08-08 at 3.17.01 PM.png>
<Screen Shot 2018-08-08 at 3.17.54 PM.png>
<Screen Shot 2018-08-08 at 3.18.17 PM.png>
<Screen Shot 2018-08-08 at 3.18.53 PM.png>
<Screen Shot 2018-08-08 at 3.22.27 PM.png>