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Author Topic: CD4:CD8 Ratio and Markers of Age-Associated Disease  (Read 1971 times)

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Offline Mishma

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CD4:CD8 Ratio and Markers of Age-Associated Disease
« on: January 14, 2014, 05:17:52 PM »
Finally a biological marker associated with premature aging that will help those of you who are having trouble obtaining disability and living a life of hell due to complications associated with diseases of aging; specifically kidney dysfunction, cardiovascular disease and lower muscle mass index and all the attendant osteoarthritis that goes with it. Of note this is independent of viral suppression and is an independent marker of mortality in the "general" population (those fortunate enough not to have HIV).

Health care/disability law should now include these conclusions followed by insurance compliance.

On a personal note my CD4 nadir was much less than those in this study (<200).


http://www.medscape.com/viewarticle/817978?src=wnl_edit_tpal&uac=177528CX

The CD4:CD8 Ratio Is Associated With Markers of Age-Associated Disease in Virally Suppressed HIV-Infected Patients With Immunological Recovery
S Serrano-Villar, S Moreno, M Fuentes-Ferrer, C Sánchez-Marcos, M Ávila, T Sainz, NGP de Villar, A Fernández-Cruz, V EstradaDisclosures
HIV Medicine. 2014;15(1):40-49.


Abstract

Objectives Inversion of the CD4:CD8 ratio (< 1) has been identified as a hallmark of inmmunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and markers of age-associated disease in treated HIV-infected patients with good immunovirological response.

Methods A cross-sectional analysis was conducted in 132 HIV-infected adults on antiretroviral therapy (ART), with plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 1 year, CD4 count > 350 cells/μL and age < 65 years. We analysed the associations between the CD4:CD8 ratio and subclinical atherosclerosis [assessed using carotid intima-media thickness (IMT)], arterial stiffness [assessed using the augmentation index (AIx)], the estimated glomerular filtration rate (eGFR), muscle wasting and sarcopenia [assessed using appendicular lean mass/height2 (ALM) measured by dual-energy X-ray absorptiometry (DEXA)].

Results CD4:CD8 ratio inversion was associated with higher IMT, lower eGFR and lower ALM (all values P < 0.05), but not with AIx. In multivariate analyses adjusted for age, sex, hypertriglyceridaemia, tobacco use and cumulative ART exposure, inversion of the CD4:CD8 ratio was independently associated with higher IMT [odds ratio (OR) 2.9; 95% confidence interval (CI) 1.2–7.1], arterial stiffness (OR 4.8; 95% CI 1.0–23.5) and lower eGFR (OR 5.2; 95% CI 1.0–64.4), but not sarcopenia (OR 0.7; 95% CI 0.2–2.7). These associations persisted when models were applied to subjects with nadir CD4 counts > 200 cells/μL and those with CD4 counts > 500 cells/μL.

Conclusions The CD4:CD8 ratio in treated HIV-infected subjects with good immunovirological response is independently associated with markers of age-associated disease. Hence, it might be a clinically useful predictor of non-AIDS-defining conditions.
2016 CD4 25% UD (less than 20). 27+ years positive. Isentress, Truvada, Acyclovir, Clonazepam, Zolpidem, Bupropion, Lisinopril, Pravastatin, Quetiapine, Doxcycline, Testosterone, Suatriptan/Naproxen, Restasis, Dorzolamide, Latanoprost, Asprin, lortab, Levothyroxine, Fioricet, Restasis, Triamclinolone, Nitrostat.

Offline Ann

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #1 on: January 15, 2014, 07:19:22 AM »
Interesting stuff; thanks for posting.

I had to look up one of the words and I suspect others also may not have seen it before (note: it's misspelled in the article, with an extra N), so here's the word and definition:

Immunosenescence: refers to the gradual deterioration of the immune system brought on by natural age advancement. It involves both the host’s capacity to respond to infections and the development of long-term immune memory, especially by vaccination. This age-associated immune deficiency is ubiquitous and found in both long- and short-living species as a function of their age relative to life expectancy rather than chronological time. It is considered a major contributory factor to the increased frequency of morbidity and mortality among the elderly. source

Those who wish to dig deeper may find the following articles interesting:

http://www.alcor.org/magazine/2013/09/26/hiv-immunosenescence-and-accelerated-aging/

http://www.immunityageing.com/content/7/1/13

http://www.immunityageing.com/content/9/1/15

There's a lot more out there too - just google "immunosenescence".
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Offline elf

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #2 on: January 15, 2014, 11:42:24 AM »
My CD4/CD8 ratio is not good (0.83), but I take 50 mg of melatonin (which has anti-aging and anti-inflammatory effects: http://www.ncbi.nlm.nih.gov/pubmed/20884126 )

Quote
Melatonin: buffering the immune system.
Carrillo-Vico A, Lardone PJ, Alvarez-Sánchez N, Rodríguez-Rodríguez A, Guerrero JM.
Author information
Abstract

Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.
http://www.ncbi.nlm.nih.gov/pubmed/23609496

-

Quote
Biogerontology. 2013 Feb;14(1):9-20. doi: 10.1007/s10522-012-9412-5. Epub 2013 Jan 3.
Psychoneuroendocrine interventions aimed at attenuating immunosenescence: a review.
Bauer ME, Muller GC, Correa BL, Vianna P, Turner JE, Bosch JA.
Author information
Abstract

There is evidence suggesting that immunosenescence can be accelerated by external factors such as chronic stress. Here we review potential psychoneuroendocrine determinants of premature aging of the immune system and discuss available interventions aimed at attenuating immunosenescence. Chronic stress may accelerate various features of immunosenescence by activating key allostatic systems, notably the hypothalamic-pituitary-adrenal axis. The immunological impact of such neuroendocrine dysregulation may be further amplified by a dramatic decline in dehydroepiandrosterone (DHEA) levels, acting in part as an endogenous glucocorticoid antagonist. Stress-buffering strategies show beneficial effects on various biomarkers in elderly populations. Likewise, supplementation of DHEA, melatonin or growth hormone has yielded significant beneficial effects in a number of studies, including: increased well-being, memory performance, bone mineral density and improved immunocompetence as evidenced by results of in vitro (T cell proliferation, cytotoxicity, cytokine production), and in vivo immune challenges. However, the side-effects of hormonal supplementation are also discussed. Finally, moderate exercise via the promotion of cortisol/DHEA balance or epigenetic modifications, is associated with lower serum pro-inflammatory cytokines, greater lymphoproliferative responses and lower counts of senescent T cells. Taken together, these data suggest that immune system is plastic and immunosenescence can be attenuated psychoneuroendocrine interventions.
http://www.ncbi.nlm.nih.gov/pubmed/23283592

Quote
Oxidative stress and immunosenescence: therapeutic effects of melatonin.
Abstract

Age-associated deterioration in the immune system, which is referred to as immunosenescence, contributes to an increased susceptibility to infectious diseases, autoimmunity, and cancer in the elderly. A summary of major changes associated with aging in immune system is described in this paper. In general, immunosenescence is characterized by reduced levels of peripheral naďve T cells derived from thymus and the loss of immature B lineage cells in the bone marrow. As for macrophages and granulocytes, they show functional decline with advancing age as evidenced by their diminished phagocytic activity and impairment of superoxide generation. The indole melatonin is mainly secreted in the pineal gland although it has been also detected in many other tissues. As circulating melatonin decreases with age coinciding with the age-related decline of the immune system, much interest has been focused on melatonin's immunomodulatory effect in recent years. Here, we underlie the antioxidant and immunoenhancing actions displayed by melatonin, thereby providing evidence for the potential application of this indoleamine as a "replacement therapy" to limit or reverse some of the effects of the changes that occur during immunosenescence.
http://www.ncbi.nlm.nih.gov/pubmed/23346283

« Last Edit: January 15, 2014, 12:01:48 PM by elf »
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Online Miss Philicia

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #3 on: January 15, 2014, 12:57:06 PM »
Mine is 1.45 which I assume is OK
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Offline buginme2

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #4 on: January 15, 2014, 01:41:47 PM »
Mine is 1.45 which I assume is OK

 Are you sure you still got teh AIDS? 

 With your 1000+ cd4  count and 1.45 ratio.

 Your the "all this science means nothing at the end of the day"  role model.


Online Miss Philicia

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #5 on: January 15, 2014, 04:31:28 PM »
Are you sure you still got teh AIDS? 

 With your 1000+ cd4  count and 1.45 ratio.

 Your the "all this science means nothing at the end of the day"  role model.



Numbers don't mean shit when I'm most likely having major rheumatologic and musculoskeletal manifestations of HIV -- my knees, ankles and feet always hurt and my thighs feel like I've been doing leg presses 24/7.  Imagine how worse off I'd be if my numbers majorly sucked.

Not sure what to tell you folks what to look forward to. Either it's HIV itself long term or it's a delayed effect from crap I was taking in '90s. First option you all lose here, the second you don't.

ps: just had new lab work done today -- result will be announced next Wednesday. Let's see if I beat my last numbers which were 1748 and 56.4% :)
"I’ve slept with enough men to know that I’m not gay"

Offline moxieinme

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #6 on: January 15, 2014, 04:47:08 PM »
Well isn't that lovely news? Always wondered about the CD4/CD8 ratio and kept track of them just for jollies.

My last labs were the first time in decades my CD4/CD8 was 0.6, with a long history of 0.1 to 0.3.

Sheesh, it's always something. As if grey hair wasn't enough.

Salvage therapy wrangler, riding the poz bronco and dodging bullets for over 24 years.
- - - - - - - - - - - - - - - - - - - - -
CD4 at diagnosis 1989 = 330
Began treatment (AZT) 1989
Lowest labs 1998: CD4=74, 7%, VL=750,000
First sustained undetectable VL in 20 years (2009); CD4=315
Current labs (12/13): CD4=637, 27%, VL=<20
Current meds: Prezista, Isentress, Intellence, Norvir

Online Miss Philicia

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #7 on: January 15, 2014, 05:14:08 PM »
For information purposes my ratio in December 2004, or almost a decade ago, was 0.74; when I was diagnosed the lowest was my second lab results and that was 0.24 in August 1993 (I have copies of my first year's worth of labs in a file, but kept nothing up to those 2004 ones).

My ratio didn't become within normal range until January 2007 -- by that time my viral load had been undetectable for six months, and my cd4 count was 702 but probably more important is that my % had gone over 40% and was then 41.3% -- so I have had a normal ratio now for seven years. For example that December 2004 reading my % was 31.1% and I'd probably just gone over 30 at that time. 14% was my lowest ever recording that first year of diagnosis.

This gives you a good picture of how you body can rebuild your immune system on paper in a span of two decades, even if thirteen of those years you were not even undetectable (though note my viral load was always stable around 40,000 so neither lowish nor super high, but still probably damaging long term).
« Last Edit: January 15, 2014, 05:19:22 PM by Miss Philicia »
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Offline buginme2

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #8 on: January 15, 2014, 07:23:37 PM »
I  think my ratio was .9ish  when diagnosed now it's 1.1 ish.

I  put little faith in this meaning anything good or bad.   I've definitely not experienced anything like P  but in my short time being positive I've grown to learn that " numbers"  do not necessarily equate to  good or bad hiv  health.

Offline tednlou2

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #9 on: January 15, 2014, 11:31:51 PM »
My last two were both 0.36.  I guess that means I have a lot of inflammation.  My CD8 is usually 1,500+.  Not on meds yet, though. 

Are the experts recommending daily aspirin for all patients, regardless of age?  I mean, unless you have issues with aspirin.  I was reading where one HIV doc recommends low dose to all patients, even if they're 25.  And, he does the inflammation marker tests, such as ESR and CRP. 

Offline moxieinme

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #10 on: January 16, 2014, 10:07:23 AM »
[ I've definitely not experienced anything like P  but in my short time being positive I've grown to learn that " numbers"  do not necessarily equate to  good or bad hiv  health.
[/quote]
This is so true. I know someone infected almost as long as myself, and we are very different on paper vs. in person. My numbers are rarely as good as his, but he's had most of the significant health issues and hospitalizations.
Salvage therapy wrangler, riding the poz bronco and dodging bullets for over 24 years.
- - - - - - - - - - - - - - - - - - - - -
CD4 at diagnosis 1989 = 330
Began treatment (AZT) 1989
Lowest labs 1998: CD4=74, 7%, VL=750,000
First sustained undetectable VL in 20 years (2009); CD4=315
Current labs (12/13): CD4=637, 27%, VL=<20
Current meds: Prezista, Isentress, Intellence, Norvir

Offline elf

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #11 on: January 16, 2014, 10:26:09 AM »
We don't know what our normal values were (when we were HIV-negative).
I've seen a medical documentation of a 9 year old asthma patient (apparently HIV negative)
and his CD4 cells were 501 (the normal range indicated was 450-2100).

I guess my normal range was with highish CD4 (around 1000) but with lowish CD4% (around 35%).
My infection after only one exposure may be due to my normal, preHIV immune status being weak.

I'm going to talk to my HIV doc how can I make my CD4% get better.
I'm taking Sustiva and Epzicom which are ''old'' drugs,
in order to boost my CD4% I would have to take entry inhibitors or integrase inhibitors
(but in my country they are available only to patients with resistant HIV strains).
« Last Edit: January 16, 2014, 10:29:32 AM by elf »
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Offline wolfter

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #12 on: January 16, 2014, 10:37:53 AM »
I'm currently at my highest % ever (around 20).  Hopefully, if they throw me a birthday party for my 50th, I'll be able to remember it.  :)

Complacency is the enemy.  ;)  Challenge yourself daily for maximum  return on investment.

Offline moxieinme

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Re: CD4:CD8 Ratio and Markers of Age-Associated Disease
« Reply #13 on: January 16, 2014, 05:36:51 PM »
I guess my normal range was with highish CD4 (around 1000) but with lowish CD4% (around 35%).
My infection after only one exposure may be due to my normal, preHIV immune status being weak.

I'm going to talk to my HIV doc how can I make my CD4% get better.
I wouldn't consider 35% lowish. My lab reports state that "normal" range for CD4% is >14.
Salvage therapy wrangler, riding the poz bronco and dodging bullets for over 24 years.
- - - - - - - - - - - - - - - - - - - - -
CD4 at diagnosis 1989 = 330
Began treatment (AZT) 1989
Lowest labs 1998: CD4=74, 7%, VL=750,000
First sustained undetectable VL in 20 years (2009); CD4=315
Current labs (12/13): CD4=637, 27%, VL=<20
Current meds: Prezista, Isentress, Intellence, Norvir

 


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