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Author Topic: gut reservoir -- use growth factors and anti-inflammatory agents restor gut  (Read 6891 times)

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Offline bimazek

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"It will be important to explore the use of growth factors and anti-inflammatory agents for accelerating the restoration of gut mucosal immune system and function during HAART," Dr. Dandekar added.

"It will be important to explore the use of growth factors and anti-inflammatory agents for accelerating the restoration of gut mucosal immune system and function during HAART," Dr. Dandekar added.

"It will be important to explore the use of growth factors and anti-inflammatory agents for accelerating the restoration of gut mucosal immune system and function during HAART," Dr. Dandekar added.HIV Therapy Does Not Completely Restore Gut Immune Function

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By Will Boggs, MD

NEW YORK (Reuters Health) Jul 31 - Treatment of HIV infection does not appear to completely restore the immune function of gut-associated lymphoid tissue (GALT), according to a report in the August issue of the Journal of Virology.

"Evaluation of gut mucosal biopsy following a period of highly active antiretroviral therapy (HAART) may be useful in getting insights into the effect of HAART on viral suppression and immune reconstitution," Dr. Satya Dandekar from University of California, Davis, told Reuters Health.

Dr. Dandekar and colleagues evaluated the suppression of HIV replication, restoration of CD4+ T cells, HIV-specific CD8+ T-cell responses, and gene expression regulating pathological processes and antiviral immune responses in longitudinal peripheral blood and gut biopsy samples of patients initiating HAART.

The study included 10 patients evaluated before starting HAART and followed for 3 years after treatment began. Three patients started HAART during primary infection, while seven started therapy during chronic.

Initiation of HAART during primary HIV infection lead to a more rapid and sustained suppression of viral burden in the peripheral blood and in GALT than did initiation of HAART during chronic HIV infection, the authors report.

Restoration of gut mucosal CD4+ T cells was slow in primary and chronic HIV patients, the results indicate, and none of the patients in the chronic HIV infection group were able to restore mucosal CD4+ T cells to normal levels during HAART.

Increased levels of HIV-specific CD8+ T cell responses suggested incomplete suppression of viral replication in GALT, the researchers note.

There was a distinct pattern of upregulated mucosal gene expression in patients with poor CD4+ T cell reconstitution in the early months after HAART initiation, the report indicates, suggesting that the extent of inflammation, cell activation, and apoptosis may directly influence the efficacy of viral suppression and CD4+ T cell restoration during therapy.

The findings show that incomplete suppression of viral replication and increased levels of immune activation and inflammation in gut tissue of HIV-infected patients receiving HAART predict a slow and incomplete restoration of gut mucosal immune system, Dr. Dandekar said.

Dr. Dandekar cited two main implications: the "gut will contribute to the replenishment of the viral reservoir by generating newly infected cells and by activating latently infected cells (due to local immune activation)," and "self renewal and replenishment of gut epithelium (as evidenced by gut gene expression studies using DNA microarrays) may remain impaired, and as a result, nutrient digestive and absorptive functions as well as drug metabolism related functions will not be optimal. This may also contribute to HIV-associated enteropathy."

"Initiation of therapy prior to the severe loss of CD4+ T cells in peripheral blood may be helpful in better restoration and maintenance of immune system, both mucosal and peripheral, and function," Dr. Dandekar continued.

"It will be important to explore the use of growth factors and anti-inflammatory agents for accelerating the restoration of gut mucosal immune system and function during HAART," Dr. Dandekar added.

Offline bimazek

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By Martha Kerr

NEW YORK (Reuters Health) Oct 03 - Patients on maximal suppression of HIV-1 continue to have viral reservoirs with high potential for replication in gut-associated lymphoid tissue (GALT).

Those findings come from a study of 15 HIV-infected patients on highly active antiretroviral therapy (HAART) conducted by Dr. Peter A. Anton and colleagues at the University of California at Los Angeles and the Aaron Diamond AIDS Research Center in New York City.

As reported in the September issue of the Journal of Acquired Immune Deficiency Syndromes, patients had been on HAART for an average of four years at baseline. Dr. Anton's team quantified HIV-1 DNA and RNA in mucosal biopsy specimens, in PBMCs and in plasma. The investigators also calculated HIV DNA burdens in each compartment and assessed decay of the reservoirs over a one-year period.

HIV-1 RNA was found in 20% of mucosal tissue samples but HIV-1 DNA was found in 80%.

The calculated number of cells containing "potentially replication-competent" HIV-1 DNA varied from 70,000 cells in PBMCs to 160,000 cells in GALT. Rates of decay were similar between the different compartments.

"The body's reservoirs of HIV do not decay over time, regardless of how well suppressed or how well adherent the subjects are with their HAART," Dr. Anton told Reuters Health.

"Current HAART alone will not lead to (HIV-1) eradication. The most likely site, we think, for this ongoing maintenance of HIV is the gut, where it is likely not just pure resting cells with HIV DNA incorporated into the cell's genome, hiding out as it were, but due to the low level cryptic replication that the gut cells, by virtue of their activated state, provide," he commented.

"As we try to move toward HIV-1 eradication, drugs with a high level of gut mucosa penetration/concentration will probably be needed in the combination," Dr. Anton said. "Several groups are at work on this, using gene therapy approaches. At present, we don't have tissue assays (as opposed to plasma assays) of drug levels. So, we don't know how much current regimens penetrate the gut lining."

Offline bimazek

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from reading more and more science articles I see that hiv even on haart or off haart with cd4 counts above say 300 is a disease of inflammation especially the gut and intestines, and hiv is a disease of a constant battle of immune system that take a toll on vitamins and such

please comment on

anti-inflammatory agents

aspirin, etc

that you are taking with or without haart to help with the

inflammatory effects of hiv

on the body




Offline bimazek

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http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030484

http://medicine.plosjournals.org/perlserv/?request=read-response&doi=10.1371/journal.pmed.0030484

does anyone know anything about this??

This past week three noteworthy papers, published in PLoS, Journal of Virology and Nature Medicine directs our attention to the gut as a critical target in HIV-1 infection and portal for therapeutic intervention.

In PLoS, Mehandru, Markowitz and colleagues report that over half of the CD4+ T cells in the gut mucosa are lost within the first few weeks after HIV-1 infection and remain consistently low, compared to peripheral blood sources, despite long term anti-retroviral therapy; furthermore, of the few CD4+ T cells that persist in the gut, a significant increase in immune activation is observed [1]. Consistent with earlier observations in SIV models, Veazey reminds us that the battle against HIV-1 should focus on the intestinal mucosa with therapeutic strategies to reduce gut immune activation [2].

The longitudinal study in J. Virology by Guadaplupe, Dandekar and co-workers showed a similar discordance in CD4+ T cells between restoration in peripheral blood and significant delay in the gut mucosa of chronic infected individuals during anti-retroviral therapy. Here, the depletion in CD4+ T cells was associated with an increase in gut immune activation, CD8+ T cells, and associated-inflammation with a corresponding decease in epithelial growth and repair-associated genes in gut mucosal tissue [3]. Consistent with this observation, Brenchley, Douek, and colleagues report in Nature Medicine that HIV infection causes a 'leaky gut' that result in the translocation of gut-derived endotoxin and the subsequent triggering of immune activation.

Collectively, these observations suggest that an orally-active therapeutic, used in conjunction with anti-retroviral therapy, be designed to both block gut-derived microbial translocation and stimulate restitution of the gut epithelium. The hope would be to restore immunological integrity of the intestinal mucosal barrier, thereby, controlling immune activation, both locally, in the gut mucosa, and systemically by suppressing cellular targets distal to the gut that directly contributes to the progression of AIDS [5-8].

The design for such an orally-active therapeutic may be found in the complex formula of bovine colostrum and ‘immune milk,’ which has long been recognized to offer passive protection to a broad number of enteric bacterial and viral pathogens, primarily via the transfer of immunoglobulins and suppression of gut associated-inflammation with promotion of mucosal repair and regeneration.

The gut in chronic HIV-1 infected individuals appears to be reminiscent of new born calves. Calves are born with a highly immature mucosal immune system and ‘leaky gut’ and, if not immediately corrected, results in death due to infection and associated-systemic immune activation. However, the cow’s first-milking rescues her calves from harmful gut microbes with a uniquely complex cocktail enriched with neutralizing polyclonal antibodies and cytokine-tissue repair factors.

Regular consumption of biologically-active bovine colostrum has been known for years to promote the development of infantile gut-associated lymphoid tissue, enhance CD4+ levels, while suppressing CD8+ and inflammatory bowl disease (IBD), including ulcerative colitis and Crohn’s disease [5]. The severity of IBD is often correlated with gut microbial-endotoxin translocation, which now appears in chronic HIV-1 infected individuals [4]. Similar to bovine colostrum, ‘immune milk’ from properly vaccinated cows affords passive immunity against bacterial, viral, and fungal infections in the human GI tract, as well as, tames gut inflammation [8].

Hence, there may be lessons learned from Bessie’s ‘immune milk.’ If viewed as a unique formula that has evolved to complement gut immunity, ‘immune milk’ may also provide relief in chronic HIV infected individuals. Initial studies have already shown that ingestion of colostrum alleviates refractory diarrhea in HIV patients with a corresponding increase in both body weight and peripheral blood CD4+ T cells [9,10]. As we learn more about the gut microenvironment in HIV infected individuals, Bessie may prove to be a worthwhile platform for the consideration of ‘immune milk’ exhibiting HIV neutralizing activity along with its innate anti-inflammatory and tissue regenerative properties.

References

1. Mehandru S. et al. PLoS 3, e484 (2006).
2. Veazey R.S., Lackner A.A. PLoS. 3, e515 (2006).
3. Guadalupe M. et al. J. Virol. 80, 8236 (2006).
4. Brenchley J.M. et al. Nat. Med. advance online publication, 19 Nov 2006.
5. Playford R.J., MacDonald C.E., Johnson W.S. Am. J. Clin. Nutr. 72, 5 (2000).
6. Korhonen, H. et al. Brit. J. Nutr. 84, S135 (2000).
7. Zeitlin L., Cone R.A., Whaley K.J. Emerg. Infect. Dis. 5, 54 (1994). 8. Green SJ, Brendsel J. Gut 55,1681 (2006).
9. Plettenberg A et al. J. Mol. Med. 71, 42 (1993).
10. Claes-Hnrik F. et al. Scandinavian J. Gastroenterology. 41, 682 (2006).

Offline J.R.E.

  • Member
  • Posts: 8,207
  • Positive since 1985, joined forums 12/03
Current Meds ; Viramune / Epzicom Eliquis, Diltiazem. Pravastatin 80mg, Ezetimibe. UPDATED 2/18/24
 Tested positive in 1985,.. In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started on  HAART on October 24th, 2003.

 As of Oct 2nd, 2023, Viral load Undetectable.
CD 4 @676 /  CD4 % @ 18 %
Lymphocytes,absolute-3815 (within range)


72 YEARS YOUNG

 


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