AIDS Study Finds No XMRV

[Cort]

Its just an abstract but a large study (almost 1000 people) looking for XMRV in AIDS found zero using quantitative real-time PCR. We don't know what sequences they looked for. My recollection is that nested PCR is better.

I looked up the researchers - they are published but not particularly well published. Why after the first couple of hundred negative samples would you keep testing? Really, what a waste of money to test
1000 people. Maybe they were from different regions across the US - so they want to get a regional analysis? It did say it was in the Multicenter Aids study.

http://www.ncbi.nlm.nih.gov/pubmed/20597166

AIDS. 2010 Jul 17;24(11):1784-5.
Absence of xenotropic murine leukemia virus-related virus in blood cells of men at risk for and infected with HIV.

Kunstman KJ, Bhattacharya T, Flaherty J, Phair JP, Wolinsky SM.
Northwestern University, Chicago, Illinois 60611, USA.
Abstract

Xenotropic murine leukemia virus-related virus has been detected in blood cells of patients with chronic fatigue syndrome and in 3.7% of healthy controls from the same geographic region. We evaluated 996 men who were participants in the Multicenter AIDS Cohort Study for xenotropic murine leukemia virus-related virus sequences in blood cells by means of a real-time quantitative PCR assay. Xenotropic murine leukemia virus-related virus was detected in none of the men on the basis of the absence of xenotropic murine leukemia virus-related virus DNA, suggesting that infection may be population-specific.

 

[Sam Carter]

AIDS. 2010 Jul 17;24(11):1784-5.
Absence of xenotropic murine leukemia virus-related virus in blood cells of men at risk for and infected with HIV.

.....
Xenotropic murine leukemia virus-related virus has been detected in blood cells of patients with chronic fatigue syndrome and in 3.7% of healthy controls from the same geographic region. ....

Xenotropic murine leukemia virus-related virus was detected in none of the men on the basis of the absence of xenotropic murine leukemia virus-related virus DNA, suggesting that infection may be population-specific.

Am I right in thinking that the authors are mistaken here? Has it not been established that Lombardi et al's samples did not all come from the same geographic region?

 

[Sam Carter]

from: http://www.sciencemag.org/cgi/content/full/328/5980/825-d

"""""""""""""""""""""""""""
Response to Comments on "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome"

Judy A. Mikovits, and Francis W. Ruscetti

....

We did not state ... that the samples analyzed ... were only from patients from documented outbreaks of CFS... In fact, only 25 samples ... came from patients identified during the 1984 to 1988 CFS outbreak in Incline Village, Nevada. The remaining 76 samples included patients with sporadic cases from 12 U.S. states and Canada, including California, New York, North Carolina, Wisconsin, Michigan, Oregon, New Mexico, New Jersey, North Dakota, Texas, and Florida. ... The healthy control population ... was composed of healthy people who visited doctors offices in the western United States between 2006 and 2008. The great majority, although not all, of the patients analyzed were matched in geographic location with controls.
"""""""""""""""""""""""""""""

 

[Cort]

Apparently they didn't check the website - although I believe the paper said they came from doctors where different outbreaks had occurred - ie not the same general region at all. I think they were making the case, or trying to make the case, for the need for a multi-center study - which this was.

 

[gu3vara]

Am I right to think that a proper study finding not XMRV in AIDS patients would be an excellent news for us? That would reinforce the idea that XMRV is not just a passenger virus that can invade an immunocompromised individual. AIDS patients are probably immunosuppressed to a certain extent even on ART right?

 

[shannah]

Am I right to think that a proper study finding not XMRV in AIDS patients would be an excellent news for us? That would reinforce the idea that XMRV is not just a passenger virus that can invade an immunocompromised individual. AIDS patients are probably immunosuppressed to a certain extent even on ART right?

Good point gu3vara ... providing the results of this study are accurate.

 

[omerbasket]

Am I right in thinking that the authors are mistaken here? Has it not been established that Lombardi et al's samples did not all come from the same geographic region?

Yes, they did, and XMRV was also found in respiratory secretions of healthy people in Germany, and in blood of healthy people in Japan. This allegation about "coming from the same region" is a lie that many people continue telling, thinking that if you'll tell a lie enough times it will catch. I hope it won't.

Now, regarding the study itself - unless the antiretrovirals that AIDS patients are on somehow eliminates XMRV or makes it impossible to detect - this study is again one of those studies that do not worth the paper on which they were wrriten on. As I said, XMRV exists in healthy people, and numerous studies have proved that. It's much harder to have a false positive than to have a false negative. Unless what I said in the first sentence of this paragraph is correct - than this study would not find XMRV even if it's there.

 

[eric_s]

Am I right to think that a proper study finding not XMRV in AIDS patients would be an excellent news for us? That would reinforce the idea that XMRV is not just a passenger virus that can invade an immunocompromised individual. AIDS patients are probably immunosuppressed to a certain extent even on ART right?

I don't think so. They should find XMRV in AIDS patients too, if the WPI and Dr. Alter are correct and it's even in the healthy population.
If they can't then either they are not able to detect it (which would be best for us obviously, if we hope the XMRV/CFS association is true) or the positive XMRV/CFS studies are at least to some degree wrong or XMRV is not present everywhere, which would mean it can hardly be the single cause for CFS.

 

[Eric Johnson from I&I]

> Why after the first couple of hundred negative samples would you keep testing? Really, what a waste of money

I have the text. Seems they already had the DNA preps sitting around from prior work. So it might have only taken about ten hours to set up all 1000 real time PCRs even though they did them in triplicate.

Anyway, there is no true positive control in this paper (which is actually just a 'letter'). Therefore it's basically a meaningless paper, considering the profound state of ignorance and confusion we are in regarding what will detect XMRV in blood-derived DNA and what won't, and why.

Could it be that HIV somehow protects people from getting XMRV, or from having the same titers in blood as other people have? I guess, but it seems very unlikely. I would bet against it at 20:1.

Detection of XMRV was confirmed at five copies by qPCR – amplifying a synthetic DNA fragment inserted into vector pCR 2.1 TOPO. The qPCR assay was validated with DNA from the 22Rv1 human prostate carcinoma epithelial cell line (American Type Tissue Collection catalog number CRL-2505D). Of the 996 peripheral blood cell DNA specimens analyzed by real-time qPCR for gag sequences, none was positive. DNA was tested in three independent experiments. All DNA specimens were positive for the CCR5 reference sequence.

 

[Eric Johnson from I&I]

> AIDS patients are probably immunosuppressed to a certain extent even on ART right?

No, I don't think they are, as long as their CD4 counts are normal (which I think they usually are). I'm not 100% certain of any of that though.

 

[Eric Johnson from I&I]

As Dr Racaniello or Dr Dove (I forget which one) said, without a true positive control this is really a futile exercise at this point. The fact that results can be all over the map -- in CFS, in prostate cancer, in healthies -- is already proven, so we learn nothing.

 

[SOC]

We need to push for a verified test/methodolgy

The lack of a verified test continues to dog us.

While these studies confirm that XMRV was not found using their particular methods, too many of these papers are concluding that because they didn't find XMRV, it isn't there. Bad science.

If XMRV exists in even a small portion of the population, 1000 samples should have shown at least one case. Or, it could be possible that if all (or most) of the patients are on HAART, the treatment is eliminating (or reducing to unmeasurably low levels), XMRV. That would be good news.

We need to get everybody using a certified, reliable test. Until that time, researchers will continue to produce low-value research.

 

[Daffodil]

how can they find XMRV by PCR when these patients are already on antiretrovirals? who designed this stupid study?

 

[ixchelkali]

Did you notice that the study was funded by an NIH extramural grant?

 

[gu3vara]

Yeah Daffodil, good point, that's totally stupid indeed, looking at antibodies would make more sense

 

[ixchelkali]

how can they find XMRV by PCR when these patients are already on antiretrovirals? who designed this stupid study?

According to their website, the Multicenter AIDS Cohort Study is a prospective study of gay and bisexual men at risk for AIDS, and only some of them are HIV-positive, so they wouldn't all be on antiretrovirals.

 

[ixchelkali]

Sorry, instead of a paragraph mark, when I hit Enter on my last post, it submitted the post. I didn't mean for it to end so abruptly.
But now I forget what else I meant to say. :Retro redface: <scratches head> Darned brain fog; I'd better slink away for a while.

 

[Gemini]

The lack of a verified test continues to dog us....
We need to get everybody using a certified, reliable test. Until that time, researchers will continue to produce low-value research.

Exactly!!!

And when we have a reliable XMRV test, these
HIV researchers should rerun their study using it.

Gemini

 

[V99]

I just sent a very polite email to Steven Wolinsky, MD, one of the authors of this paper, explaining why his statement, "...in 3.7% of healthy controls from the same geographic region", is incorrect.

 

[Daffodil]

well i wish someone would contact the CFS patients who improved on antiretovirals and study them instead of wasting all this time. this is such BS. the virus is not going to stop because they cannot afford another retrovirus! wtf