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Author Topic: Study Suggests Unidentified Source Of Residual Viremia on HAART  (Read 2078 times)

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Offline J220

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Hiding in plain sight???? So what this shows is that when someone goes off HAART it is not latent infected CD4 cells that cause a rebound, but some other unidentified source!! Yet this unidentified source is still affected by HAART, but not to the extent of extinction.


From http://www.sciencedaily.com/releases/2009/08/090825082656.htm

ScienceDaily (Aug. 25, 2009) A new study suggests that an unidentified cellular source may be responsible for residual viremia in HIV-1 patients on highly active antiretroviral therapy (HAART). This discovery disputes previous theories that attributed residual viremia to latent proviruses in resting CD4+ T cells and could significantly impact eradication efforts.

The researchers from The Johns Hopkins University School of Medicine, Baltimore, Maryland; The University of Texas, Austin; and the Howard Hughes Medical Institute, Baltimore, Maryland report their findings in the September 2009 issue of the Journal of Virology.

When successful, HAART can reduce HIV-1 levels in the blood to undetectable amounts, however, HIV-1 still persists as latent proviruses in resting CD4+ T cells, also known as residual viremia. Current eradication strategies have focused on these latent T cell reservoirs, however, treatment failure has prompted researchers to examine other cellular reservoirs as potential sources of residual viremia.

Using two different methods, researchers analyzed viral sequences from individual patients to determine whether residual viremia was stemming from a source other than latent resting CD4+ T cells. Results showed residual viremia to be genetically distinct from proviruses in activated CD4+ T cells.

"The finding that some of the residual viremia in patients on HAART stems from an unidentified cellular source other than CD4+ T cells has implications for eradication efforts," say the researchers.
« Last Edit: August 25, 2009, 11:25:02 AM by J220 »
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Offline Inchlingblue

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Re: Study Suggests Unidentified Source Of Residual Viremia on HAART
« Reply #1 on: August 25, 2009, 11:58:10 AM »
Siciliano mentioned this at the last CROI:

I'm going to argue that the residual viremia is due to release of the virus from stable reservoirs. We have directly analyzed the residual viremia. We don't see evidence for it evolving. What we do see, though, is that it seems to be coming from at least two different sources: this latent reservoir in T cells that we described a long time ago, and another -- as yet unidentified -- reservoir.

There was another study, however, that has found residual viremia is coming from two different kinds of Tcells:

HIV persists in a reservoir of latently infected CD4+ T cells in individuals treated with highly active antiretroviral therapy (HAART). Here we identify central memory (TCM) and transitional memory (TTM) CD4+ T cells as the major cellular reservoirs for HIV and find that viral persistence is ensured by two different mechanisms. HIV primarily persists in TCM cells in subjects showing reconstitution of the CD4+ compartment upon HAART. This reservoir is maintained through T cell survival and low-level antigen-driven proliferation and is slowly depleted with time. In contrast, proviral DNA is preferentially detected in TTM cells from aviremic individuals with low CD4+ counts and higher amounts of interleukin-7-mediated homeostatic proliferation, a mechanism that ensures the persistence of these cells. Our results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and, as in cancer, drugs that interfere with the self renewal and persistence of proliferating memory T cells.

It seems that reservoir size and number of reservoirs is contingent on how long a person has had HIV without starting HAART. Based on reading the article in Science Daily one can't tell the HIV history of the individuals in Siciliano's study. In other words, different individuals' reservoirs are likely to vary in both size and type, based on factors such as length of time with HIV and when HAART was initiated. It doesn't seem to be a "one size fits all" answer.

LINKS:

http://www.thebody.com/content/toparts/art50467.html#commentAdd

http://www.natap.org/2009/HIV/062609_01.htm

The article in Science Daily does not seem to be an accurate overview of the study. The only way to know what this study found is to read the article in Journal of Virology.

It's these kinds of seemingly conflicting results that concerns me as far as what seems like scientists in the field not communicating with each other, not knowing about one another's research, etc
« Last Edit: August 25, 2009, 01:50:03 PM by Inchlingblue »

Offline brazilianman

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Re: Study Suggests Unidentified Source Of Residual Viremia on HAART
« Reply #2 on: August 25, 2009, 02:56:02 PM »
Inch

this study was not to end the latent reservoirs?

www.news-medical.net/news/2009/.../46991.aspx

the medication exists.
what is lacking to test?

Offline brazilianman

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Offline brazilianman

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Re: Study Suggests Unidentified Source Of Residual Viremia on HAART
« Reply #4 on: August 25, 2009, 04:20:04 PM »
e-mail  DR. Boris Matija Peterlin

<Matija.Peterlin@ucsf.edu>

Offline Inchlingblue

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Re: Study Suggests Unidentified Source Of Residual Viremia on HAART
« Reply #5 on: August 25, 2009, 04:43:10 PM »
Inch

this study was not to end the latent reservoirs?

www.news-medical.net/news/2009/.../46991.aspx

the medication exists.
what is lacking to test?

This link didn't work.

The other two links mention HDAC and SAHA as possible ways to wake up dormant HIV. It still has not been tested on people but this is what was discussed in the threads "Waking up Dormant HIV," (Zolinza is SAHA) and also "Shock and Kill" and "Targeted Chemotherapy" threads.

Offline elf

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Re: Study Suggests Unidentified Source Of Residual Viremia on HAART
« Reply #6 on: August 28, 2009, 03:05:48 AM »
Hiding in plain sight???? So what this shows is that when someone goes off HAART it is not latent infected CD4 cells that cause a rebound, but some other unidentified source!!

Remember that when people are uncountable, viral load is never zero, it it lower than 50 (or 40)
usually low around 10, but never zero.

When a person goes off HAART, the virus suddenly starts replicating in blood and enters
UNINFECTED cells. It's what happens when a person misses two or more consecutive doses of meds.  :-\
In the 1st 3 days off meds there is a high jump of viral load, then CD4 go down, and viral load go skyhigh as CD4 are destroyed by the replicating virus.

The bigger problem about going off HAART is potential resistance. Resistance is more frequent with meds that stay longer in the bloodstream (for example: Sustiva) than with meds that clear themselves rapidly (for example: Kaletra), continuous low(er) concentrations of meds enable the virus to learn how to ''cheat'' (that is, to become med-resistant).
« Last Edit: August 28, 2009, 03:10:10 AM by elf »

 


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