{"id":1974,"date":"2011-09-24T05:44:22","date_gmt":"2011-09-24T09:44:22","guid":{"rendered":"http:\/\/blogs.nejm.org\/?p=1974"},"modified":"2015-06-04T15:15:44","modified_gmt":"2015-06-04T19:15:44","slug":"warning-viral-replication-is-hazardous-to-your-health","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/warning-viral-replication-is-hazardous-to-your-health\/2011\/09\/24\/","title":{"rendered":"Warning: Viral Replication is Hazardous to Your Health"},"content":{"rendered":"<p><a href=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2011\/09\/perpetual-motion-machine1.gif\"><img loading=\"lazy\" decoding=\"async\" class=\"alignright size-full wp-image-1981\" title=\"perpetual-motion-machine\" src=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2011\/09\/perpetual-motion-machine1.gif\" alt=\"\" width=\"135\" height=\"134\" \/><\/a>When studies evaluate the prognostic importance of measuring HIV viral load, they generally do so by assessing a single measurement rather than values obtained longitudinally. \u00a0One obvious limitation of this approach is that baseline VL poorly predicts outcome after ART initiation &#8212; a finding in stark contrast to the <a href=\"http:\/\/www.sciencemag.org\/content\/272\/5265\/1167.abstract\" target=\"_blank\">original description of VL<\/a> from the MACS cohort prior to effective HIV therapy.<\/p>\n<p>Now, <a href=\"http:\/\/dx.doi.org\/10.1093\/cid\/cir526\">a collaborative group of researchers<\/a> report the effect of something they call &#8220;viremia copy-years,&#8221; a marker of cumulative exposure to viral replication. This &#8220;area under the viral load&#8221; curve was calculated in 2027 patients starting ART at eight US sites from 2000-2008. \u00a0Total number of VL measurements was a whopping 21,665.<\/p>\n<p>The results are striking: \u00a0viremia copy-years strongly predicted all-cause mortality &#8212;\u00a0and did so more powerfully than either cross-sectional VL measurements or CD4-cell count. \u00a0Each 1-unit increase in log10 copy years\/mL was independently\u00a0associated with a 44% increase in mortality risk.<\/p>\n<p>The take-home message from this skillfully done study is that <em>viral replication is bad for your health<\/em> &#8212; even if your CD4-cell count is OK. \u00a0And why might this be the case? \u00a0The authors write:<\/p>\n<blockquote><p>We speculate the number of viremia copy-years, as a measure of cumulative plasma HIV burden, serves as a surrogate for and perhaps is the underlying driver of cumulative inflammation and immune system activation that approximates such long-term inflammatory biomarker effects.<\/p><\/blockquote>\n<p>A few other thoughts:<\/p>\n<ul>\n<li>Is high viremia copy-years a lab proxy for poor medication adherence? \u00a0Probably &#8212; but this doesn&#8217;t invalidate the results.<\/li>\n<li>Of course in clinical practice, few of us have the calculus skills (remember integrals?) actually to calculate something like an area under the viral load curve. OK, <em>I<\/em> don&#8217;t have the math skills.<\/li>\n<li>A study evaluating whether\u00a0<em>pre<\/em>-ART viremia copy-years influences prognosis would be particularly fascinating &#8212;\u00a0and highly relevant for the when-to-start question.<\/li>\n<li>The results reinforce the findings from\u00a0<a href=\"http:\/\/jid.oxfordjournals.org\/content\/200\/1\/79.full\" target=\"_blank\">this interesting study<\/a> linking time of uncontrolled viral replication to an increased risk of lymphoma &#8212; paper summarized in <em><a href=\"http:\/\/aids-clinical-care.jwatch.org\/cgi\/content\/full\/2009\/622\/4?ijkey=jy8ifLfcVoeZA&amp;keytype=ref&amp;siteid=jnlwatch\">Journal Watch AIDS Clinical Care<\/a><\/em>.<\/li>\n<\/ul>\n<p>So even though we are unlikely to start using this viremia copy-years value in clinical practice, these data certainly make intuitive sense &#8212; and reinforce the notion that getting this lethal virus under control is the logical way to improve outcomes.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>When studies evaluate the prognostic importance of measuring HIV viral load, they generally do so by assessing a single measurement rather than values obtained longitudinally. \u00a0One obvious limitation of this approach is that baseline VL poorly predicts outcome after ART initiation &#8212; a finding in stark contrast to the original description of VL from the [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,4,8,10],"tags":[423,444,977,978],"class_list":["post-1974","post","type-post","status-publish","format-standard","hentry","category-health-care","category-hiv","category-patient-care","category-research","tag-hiv","tag-hiv-rna","tag-viral-load","tag-viral-replication"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/1974","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=1974"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/1974\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=1974"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=1974"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=1974"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}