POZ Community Forums
Meds, Mind, Body & Benefits => Research News & Studies => Topic started by: Boze on July 16, 2010, 07:09:30 pm
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http://www.latimes.com/news/health/la-heb-0716-hiv-20100716,0,4884118,print.story
HIV can be deadly even before CD4 counts fall, researchers say
By Thomas H. Maugh II, Los Angeles Times
11:13 AM PDT, July 16, 2010
An infection by the virus that causes AIDS can increase risk of premature death even before the immune system has deteriorated to the point where most physicians begin antiviral therapy, British researchers said Thursday.
An infection by the virus that causes AIDS can increase risk of premature death even before the immune system has deteriorated to the point where most physicians begin antiviral therapy, British researchers reported Thursday. The finding suggests that treatment should start even earlier than it is now and supports the current plans of world bodies to begin treating HIV infections in the developing world earlier.
The most common marker of an HIV infection is the level of an immune cell called CD4 that is the target of the virus. In a healthy individual, CD4 levels are generally over 500 cells per cubic millimeter and can go as high as 1,500. A level below 200 sharply increases the risk of the infections and other illnesses that are the markers for full-blown AIDS. Most physicians in the industrial world now begin treatment when a patient's CD4 levels fall below 350. In the developing world — at least in part because of the shortage of resources — treatment has generally begun when the level falls to 200, but UNAIDS announced last week that it would now begin treatment at 350.
Epidemiologist Rebecca Lodwick of the University College London Medical School and her colleagues analyzed data from 23 North American and European cohorts of HIV-positive individuals between the ages of 20 and 29. They reported in the journal Lancet that, when they accounted for other factors affecting deaths, homosexual men with counts between 350 and 500 and who had not received antiviral therapy were 30% more likely than uninfected individuals to die. Heterosexuals were nearly three times as likely to die, injection drug users were more than nine times as likely to die, and those with unknown risk factors were four and one-half times as likely to die.
"The increase in risk was substantial in injecting drug users and the heterosexual group, but was small in men who have sex with men," the authors said in a statement. "This finding suggests that much of the raised risk in the former two risk groups probably results from confounding by socioeconomic and lifestyle factors rather than being an effect of HIV infection itself. The magnitude of the raised risk in the [homosexual] group is more likely to reflect the effect of HIV itself."
Whether starting therapy even earlier than is now done would reduce this increased risk is not known, researchers from the Harvard Medical School wrote in an editorial in the same journal. A clinical trial to test this possibility is now underway, but results are not expected for several years. Meanwhile, they said, physicians should aggressively screen for, prevent and treat risk factors that might contribute to the increased risk.
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What on earth are these people dying of?
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What on earth are these people dying of?
To be honest, i'm pretty skeptical of such studies. They looked at death rates of people in their 20s - which is minuscule for health-related causes (ie not car accidents or overdoses) in the first place. So a 30% increase is still a very, very small number. The number for British Columbia is about 90 per 100,000 for ALL causes (http://www.injuryresearch.bc.ca/admin/DocUpload/3_20070202_142123Number%20of%20Deaths%20and%20Average%20Annual%20Mortality%20Rates%20by%20Sex%20&%20Age%20Group.pdf) - and I think majority are not health-related.
The reason I have a big problem with such studies is that they are used to estimate 'years to live' for HIV+ people. Since their methodology is suspect to me (ie estimating mortality increase for HV+), I am not sure I can believe their sanguine results.
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Man, these studies always cause me anxiety. I, too, would like to know what these people died from. When I got bacterial pneumonia, the doc told me if I hadn't come in to the ER when I did, I would have died. Are they talking about that kind of situation? People with good numbers but got the flu or pneumonia and let it go too long?
Whenever I've asked my doc, Dr Gallant, and others about the risk of dying waiting around for CD4 of 350-500 to start meds, they've all said that isn't something to worry about. They did say long-term, untreated HIV is not good. And, I've read where a few HIV docs say they have had young people with good numbers die. They didn't explain what they died from. I've wondered for a long time whether there are HIVers not on meds with good numbers who the virus acts differently. Is it causing damage, but the CD4 and viral load aren't showing it? CBC labs aren't showing problems? For someone poz for 9 years and not on meds, would it be a good idea for a 34 year-old to have more sophisticated tests--stress test, etc? My mom had a heart valve replaced and it was suggested that my brother and I have an echo test (think that's what it is) to check ours as her problem could be hereditary they said. It makes me wonder whether having HIV means I should take those kindS of things more seriously. When you're 34, most docs would say testing for things I've described would be a waste of money. They will say all your labs look good, so what are you worried about?
So, it would be good to know what these people died from. Were they perfectly healthy (seemingly) and had some major heart attack? Got sick with the flu and just didn't handle it very well like their negative counterparts would?
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http://www.aidsmap.com/en/news/984201EA-67BF-4B13-9374-71ED1D7B42B8.asp?Tracking=Bulletin&Referrer=1413744
Inflammation associated with increased mortality risk for patients with HIV, even when CD4 cell count high.
High levels of two markers of inflammation – fibrinogen and C-reactive protein – are independently associated with an increased risk of mortality for patients with HIV, even when they have a strong immune system, US investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.
“We found that elevated levels of fibrinogen and CRP [C-reactive protein] were strong and independent predictors of 5-year mortality risk. Our findings suggest an important role for inflammation in mortality risk”, comment the investigators.
The study’s findings could help explain why, despite effective antiretroviral therapy, mortality rates remain higher amongst individuals with HIV than in the general population.
Only one earlier study (the SMART treatment interruption study) has found an association between inflammation and an increased risk of mortality for HIV-positive patients in the era of modern antiretroviral therapy. This research showed that there was a strong association between levels of the inflammatory markers D-dimer, Il-6, and C-reactive protein and mortality.
Separate research conducted by investigators from the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study group identified an association between HIV and elevated levels of fibrinogen, an inflammatory marker connected with clotting.
The FRAM investigators hypothesised that inflammation, indicated by elevated levels of fibrinogen and C-reactive protein, would be independently associated with an increased risk of death during five years of follow-up in their cohort of 922 patients.
The patients were stratified according to their baseline fibrinogen levels ( below 319 mg/ml; 319-406 mg/dl; and above 406 mg/dl), and according to their CD4 cell counts (below 200; 200-350; 350-500; and, above 500 cells/mm3).
Compared to individuals with lowest fibrinogen levels, those with fibrinogen above 406 mg/dl were significantly older (41 vs. 43years, p = 0.008), were more likely to be African American (29 vs. 50%, p = 0.018), to be using medication to control blood pressure (12 vs. 16%, p 0.012), to have higher total cholesterol p = 0.014) and lower HDL cholesterol (p = 0.041) and to have higher levels of C-reactive protein (p < 0.0001).
Over the five-year period of the study, individuals with the highest fibrinogen had a mortality rate of 25% compared to a rate of just 7% for those with the lowest fibrinogen levels.
Mortality rates also differed according to baseline levels of C-reactive protein. Individuals with a C-reactive protein level above 3 mg/dl had a mortality rate of 19% compared to a rate of 7% for those with C-reactive protein levels below 1 mg/dl.
Compared to individuals with fibrinogen below 319 mg/ml, those with the levels of this marker of inflammation had a three-fold increase in their mortality risk (OR = 3.35; 95% CI, 1.99-5.65, p < 0.001).
In addition, high levels of C-reactive protein were also significantly associated with an increased risk of death, the mortality risk being almost four-fold higher for those with a level above 3 mg/dl than those with C-reactive protein below 1 mg/dl (OR = 3.72; 95% CI, 2.09-6.63, p < 0.001).
When fibrinogen and C-reactive protein were included in a model together, high levels of both remained independently associated with an increased risk of death (fibrinogen, p = 0.001; C-reactive protein, p = 0.002).
Next the investigators examined the relationship between CD4 cell count, inflammation and mortality.
In every CD4 cell category, each 100 mg/dl increase in fibrinogen increased the risk of death (1.93 for those with a CD4 cell count below 200 cells/mm3; 1.30 for those with a CD4 cell count above 500 cells/mm3).
Even when the investigators adjusted their results for evidence of renal disease, higher levels of both markers were associated with an increased risk of mortality in each CD4 cell category.
“We conclude”, write the investigators, “that elevated levels of fibrinogen and CRP are strong and independent predictors of all-cause mortality in HIV-infected adults.”
They continue, “our findings that fibrinogen and CRP remained associated with higher odds of death regardless of the degree of immunosuppression suggests that inflammation remains an important factor even in those with relatively preserved CD4 cells.”
The investigators call for further research “to determine whether interventions to reduce fibrinogen and CRP levels might decrease mortality risk in HIV-infected adults.”
Reference
Tien PC et al. Inflammation and mortality in HIV-infected adults: analysis of the FRAM cohort study. J Acquir Immune Defic Syndr, advance online publication, July 2010.
aidsmap resources
Medical tests news
* Kidney disease increases mortality for women with AIDS starting HIV treatment
* Viral load increases in cells predicts CD4 cell decline in asymptomatic patients
* Malaria symptoms should raise suspicion of HIV in sub-Saharan Africa
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I found more details from the study. This is good as it actually quantifies the difference in mortality based on CD4 count:
""An analysis of 401 of 419 deaths revealed that the risk of death compared to the general population was 30 percent higher for men who have sex with men, 2.94 times higher for heterosexuals, 9.37 times higher for injection drug users, and 4.57 times higher for those with other or unknown risk factors," the researchers reported, according to HealthDay News (7/15).
"The relatively low rate for men who have sex with men suggests that unmeasured confounders – such as lifestyle and socioeconomic factors – might play a role in the high rates for the other groups, the researchers said," MedPage Today continues (7/15).
However, when compared to patients with CD4 counts between 350 and 499, the death rate was 23 percent lower in patients with counts of 500-699 and 34 percent lower with patients with counts at or above 700, according to the Lancet study. "Because ART might reduce the risk of death in such patients, these findings support the need for continuing studies (such as the START trial and further exploration of existing observational databases) of the risks and benefits of starting ART at CD4 counts greater than 350 cells per μL," the authors conclude (Study Group on Death Rates at High CD4 Count in Antiretroviral Naive Patients, 7/16)."
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I ain't dead yet and that's all I need to know. :)
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I ain't dead yet and that's all I need to know. :)
Even better to have ccr5 mutation http://en.wikipedia.org/wiki/CCR5#HIV (http://en.wikipedia.org/wiki/CCR5#HIV) :)
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So, can we go to our docs and ask to have those tests for the inflammatory markers? If ya can, what can you do if the numbers aren't good? Or, do you just take all these studies with a grain of salt? Are they like the "don't eat eggs..okay, eggs aren't so bad" or "red wine is good for you...but you'd have to drink gallons of it."
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So, can we go to our docs and ask to have those tests for the inflammatory markers? If ya can, what can you do if the numbers aren't good?
Good question, And I don't know the answer to that. I only received that in the mail the other day. I've printed it out, and I will ask my doctor about it on my next visit. I see my primary tomorrow, and I am also going to ask her about.
Perhaps others with more knowledge can help answer that. I always understood that inflammation and HIV go hand in hand.
Ray
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tednlou and Ray,
You can request both tests (CRP and Fibrinogen). There is not much you can do for high fibrinogen, directly. You have to try and control the inflammation. Fibrinogen is usually ordered if your having clotting issues. CRP should be routine. You have probably already been tested for it.
v
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Thanks for that !
I thought that was familiar, but I was looking at my last blood test results, and I don't see it listed. I'll have to check some other tests.
The only tests shown were:
SODIUM
POTASSIUM
CHLORIDE
CARBON DIOXIDE
ANION GAP
GLUCOSE
UREA NITROGEN
CREATININE
CALCIUM
TOTAL PROTEIN
ALBUMIN
ALKALINE PHOSPHATASE
AST
ALT
BILIRUBIN TOTAL
eGFR
WBC
RBC
HGB
HCT
MCV
MCH
MCHC
RDWSD
PLT
MPV
NE#
LY#
EO#
BA#
INM GRAN3
NE%
LY%
MO%
EO%
BA%
IMN GRAN%
Ray