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Author Topic: HIV Replication in Lymphatic Tissues  (Read 3585 times)

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Offline Mishma

  • Member
  • Posts: 234
  • HIV drugs are our Allies but hardly our Friends
    • Marquis de Vauban
HIV Replication in Lymphatic Tissues
« on: February 06, 2014, 12:16:46 am »
This is old news in a sense but one that has to be continually reinforced to non Infectious Disease specialists. As one who suffers from chronic inflammation with Lupus like symptoms, polyneuropathy and neurological BS it gets my goat whenever another health care professional says, "Your HIV is well controlled-just look at your labs." Viral burden is routinely measured in our bloodstream but not in our lymphatic tissues-where the majority of our immune cells reside. Poor penetration of this tissue by our current drugs is insufficient to eradicate the virus and it is suggested that low concentrations of the drugs in these tissues actually supports ongoing replication. 


HIV/AIDS
How Much Do Drugs Matter?
Anandi N. Sheth

http://stm.sciencemag.org/content/6/222/222ec25.short

or the original article: http://www.pnas.org/content/early/2014/01/23/1318249111.full.pdf+html

Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30308, USA. E-mail: ansheth@emory.edu

Antiretroviral drugs have increased life expectancy and improved quality of life for HIV-infected patients. However, although these drugs suppress HIV replication in the blood, they do not eliminate HIV-infected cells. Hence, current treatment cannot cure the infection and must be lifelong. Indeed, even treated HIV-infected patients have persistent immune system abnormalities, including incomplete immune restoration, chronic inflammation, and their sequelae. One explanation for these ongoing complications is that viral replication may persist in the lymphatic tissues, the network of immune cells located in the lymph nodes, gut, and other organs in which most HIV is produced and stored.

Fletcher et al. explored the hypothesis that antiretroviral drug concentrations may be insufficient to completely suppress HIV replication in lymphatic tissues. The authors followed 12 HIV-infected patients who were starting antiretroviral therapy and collected their blood, lymph node, and gut samples at frequent intervals over 6 months. The authors used specialized techniques to measure antiretroviral drug concentrations inside the immune cells in these tissues. Interestingly, the drug levels inside immune cells from the lymphatic tissues were lower than inside immune cells from the blood. The authors then sought to determine whether these drug levels were suppressing virus replication in the lymphatic tissues. They measured the amount and location of virus produced in the lymphatic tissues and found, in four out of nine patients with sufficient data for analysis, evidence that the virus was continuing to replicate in these tissues, even when it was fully suppressed in the blood. Last, the authors found a direct correlation between drug levels and the quantity of viral replication in the tissues.

This study demonstrates that HIV continues to replicate in the lymphatic tissues of some HIV-infected patients receiving therapy despite suppression of viral replication in the blood. Additionally, the study supports that low concentrations of anti-HIV drugs may contribute to this ongoing replication in the tissues. This study importantly suggests that strategies to improve drug penetration into lymphatic cells could overall reduce viral replication. Fully suppressing viral replication in all sites could improve the long-term consequences of HIV infection and provide the first step toward a cure.

C. V. Fletcher et al., Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc. Natl. Acad. Sci. U.S.A., published online 27 January 2014 (10.1073/pnas.1318249111). [Full Text]
« Last Edit: February 06, 2014, 12:20:02 am by Mishma »
2016 CD4 25% UD (less than 20). 30+ years positive. Dolutegravir, Acyclovir, Clonazepam, Lisinopril, Quetiapine, Sumatriptan/Naproxen, Restasis, Latanoprost, Asprin, Levothyroxine, Restasis, Triamcinolone.

Offline Mishma

  • Member
  • Posts: 234
  • HIV drugs are our Allies but hardly our Friends
    • Marquis de Vauban
Re: HIV Replication in Lymphatic Tissues
« Reply #1 on: February 08, 2014, 02:09:51 pm »
Reason for hope: "This study importantly suggests that strategies to improve drug penetration into lymphatic cells could overall reduce viral replication. Fully suppressing viral replication in all sites could improve the long-term consequences of HIV infection and provide the first step toward a cure."
2016 CD4 25% UD (less than 20). 30+ years positive. Dolutegravir, Acyclovir, Clonazepam, Lisinopril, Quetiapine, Sumatriptan/Naproxen, Restasis, Latanoprost, Asprin, Levothyroxine, Restasis, Triamcinolone.

Offline Mishma

  • Member
  • Posts: 234
  • HIV drugs are our Allies but hardly our Friends
    • Marquis de Vauban
Re: HIV Replication in Lymphatic Tissues
« Reply #2 on: February 18, 2014, 02:04:08 pm »
From Nature: Radioactive tracers map spread of HIV

http://www.nature.com/news/radioactive-tracers-map-spread-of-hiv-analogue-1.14704?WT.ec_id=NEWS-20140218

"Hidden virus

Some monkeys controlled the infection, either naturally or after treatment with antiretroviral drugs, and had undetectable levels of virus in their blood plasma. But the scanning images showed a residual signal in the small intestines, lymph tissues and male reproductive tract, although none was present in the large intestines."
2016 CD4 25% UD (less than 20). 30+ years positive. Dolutegravir, Acyclovir, Clonazepam, Lisinopril, Quetiapine, Sumatriptan/Naproxen, Restasis, Latanoprost, Asprin, Levothyroxine, Restasis, Triamcinolone.

Offline xinyuan

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  • Posts: 202
Re: HIV Replication in Lymphatic Tissues
« Reply #3 on: February 18, 2014, 08:15:51 pm »
Although we already know about these reservoirs, that we're closer to mapping it is exciting.

A feasible step closer toward focused eradication.

Thanks for the link.

 


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