{"id":1131,"date":"2010-11-04T08:16:36","date_gmt":"2010-11-04T12:16:36","guid":{"rendered":"http:\/\/blogs.nejm.org\/?p=1131"},"modified":"2015-06-04T15:24:29","modified_gmt":"2015-06-04T19:24:29","slug":"xmrv-and-cfs-more-yay-and-nay","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/xmrv-and-cfs-more-yay-and-nay\/2010\/11\/04\/","title":{"rendered":"XMRV and CFS:  More Yay and Nay"},"content":{"rendered":"<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright size-full wp-image-1157\" title=\"letter_x\" src=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2010\/11\/letter_x1.jpg\" alt=\"letter_x\" width=\"320\" height=\"214\" \/>Does XMRV cause Chronic Fatigue Syndrome?\u00a0 Or more accurately, is it even <em>associated <\/em>with CFS?<\/p>\n<p>I&#8217;ve been putting off writing about this for a while, as I knew colleagues of mine had a paper in press on the topic, and I wanted the dust to settle a bit more on the controversy.<\/p>\n<p>But of course the controversy, and the scientific inquiry, are\u00a0just getting started. There was a recent <a href=\"http:\/\/hhs.granicus.com\/viewpublisher.php?view_id=5\" target=\"_blank\">HHS meeting<\/a> on the topic;\u00a0anecdotal reports of patients with CFS receiving antiretroviral agents for treatment;\u00a0\u00a0patients with the condition have been <a href=\"http:\/\/jama.ama-assn.org\/cgi\/content\/full\/304\/15\/1653\" target=\"_blank\">discouraged by one group\u00a0from donating blood<\/a>.<\/p>\n<p>Now, my colleagues&#8217; paper has been <a href=\"http:\/\/www.journals.uchicago.edu\/doi\/abs\/10.1086\/657168\" target=\"_blank\">published in <em>The Journal of Infectious Diseases<\/em> <\/a>&#8212; and it shows <em>no detection of\u00a0XMRV<\/em> in patients with CFS, and furthermore no XMRV in comparison groups of patients with HIV, rheumatoid arthritis, transplantation, or a group just presenting for general medical care.<\/p>\n<p>The score is getting hard to tally, especially because negative studies get way less press. On the plus side, there was the <a href=\"http:\/\/www.sciencemag.org\/cgi\/content\/abstract\/1179052\" target=\"_blank\">original Science paper<\/a> that got the field started, and the more recent <a href=\"http:\/\/www.pnas.org\/content\/early\/2010\/08\/16\/1006901107.abstract\" target=\"_blank\">PNAS one<\/a>; the latter, oddly, found a slightly different retrovirus (MLV).<\/p>\n<p>On the minus side?\u00a0 In addition to the <em>JID<\/em> paper from Boston,\u00a0there have been negative studies\u00a0from the <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20185493?dopt=Abstract\" target=\"_blank\">Netherlands<\/a> and two from Britain (<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20156349?dopt=Abstract\" target=\"_blank\">here<\/a> and <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20066031?dopt=Abstract\" target=\"_blank\">here<\/a>).<\/p>\n<p>I am sure there are many others in various stages of gestation.<\/p>\n<p>How could highly-qualified scientists come to such disparate conclusions?\u00a0 Here are some admittedly unoriginal thoughts:<\/p>\n<ul>\n<li>CFS has many causes.\u00a0 (See <a href=\"http:\/\/blogs.nejm.org\/index.php\/hey-didnt-you-used-to-be-the-cause-of-cfs\/2010\/01\/17\/\" target=\"_blank\">here<\/a> for my view.)<\/li>\n<li>Related:\u00a0 Some CFS is of the &#8220;epidemic&#8221; variety; sporadic cases are different, less likely to be caused by infection.<\/li>\n<li>Geographic variability in XMRV incidence\/prevalence.<\/li>\n<li>Different assays and\/or different primers used in different labs.<\/li>\n<li>Contamination of assays.\u00a0 (It is PCR, after all.\u00a0 Isn&#8217;t that an inherent risk for any highly-sensitive amplification procedure?)<\/li>\n<li>Replication of XMRV is variable, or low level, a la HTLV-1 or HIV in &#8220;elite controllers.&#8221;<\/li>\n<li>XMRV detection is an epiphenomenon, and &#8220;true-true, and unrelated&#8221; &#8212; hence detection of the virus may be a random event, or merely an association.<\/li>\n<li>Some other issue no one has thought of.<\/li>\n<\/ul>\n<p>Regardless, I highly recommend the <a href=\"http:\/\/www.journals.uchicago.edu\/doi\/abs\/10.1086\/657169\">editorial by\u00a0Mary\u00a0Kearney and\u00a0Frank\u00a0Maldarelli<\/a> that appears in the same issue.\u00a0 They call for the following:<\/p>\n<ol>\n<li>Standardization of detection assays.<\/li>\n<li>Prospective epidemiologic surveys.<\/li>\n<li>Sharing reagents and samples. [<em><strong>Amazing<\/strong> this hasn&#8217;t been done yet!]<\/em><\/li>\n<li>Comprehensive and rigorous phylogenetic sequence analysis.<\/li>\n<li>Development of tractable animal models.<\/li>\n<\/ol>\n<p>In addition, they have strong words for those who are prescribing antiretrovirals for individuals with CFS:<\/p>\n<blockquote><p>At this time, such an approach is premature and medically indefensible outside the secure oversight of a well\u2010controlled clinical trial. \u201cReal world\u201d coping with severe diseases like chronic fatigue syndrome and prostate cancer creates understandable desperation on the part of patients, caregivers, and health care professionals. Such pressures are not justification for testing of therapies in an uncontrolled manner. Indeed, because they are of no help whatsoever to other patients, physicians, pharmaceutical companies, or regulatory agencies, such uncontrolled therapy works directly against the goal of providing effective therapy to the million or more individuals experiencing these serious conditions.<\/p><\/blockquote>\n<p>Wise words indeed.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Does XMRV cause Chronic Fatigue Syndrome?\u00a0 Or more accurately, is it even associated with CFS? I&#8217;ve been putting off writing about this for a while, as I knew colleagues of mine had a paper in press on the topic, and I wanted the dust to settle a bit more on the controversy. But of course [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,5,8],"tags":[178,182,622,1000],"class_list":["post-1131","post","type-post","status-publish","format-standard","hentry","category-health-care","category-infectious-diseases","category-patient-care","tag-cfs","tag-chronic-fatigue","tag-mlv","tag-xmrv"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/1131","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/comments?post=1131"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/1131\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=1131"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=1131"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=1131"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}