{"id":1984,"date":"2011-10-03T22:52:45","date_gmt":"2011-10-04T02:52:45","guid":{"rendered":"http:\/\/blogs.nejm.org\/?p=1984"},"modified":"2015-06-04T15:15:43","modified_gmt":"2015-06-04T19:15:43","slug":"cascade-when-to-start-yet-another-take","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/cascade-when-to-start-yet-another-take\/2011\/10\/03\/","title":{"rendered":"CASCADE: When to Start, (Yet) Another Take"},"content":{"rendered":"

\"\"<\/a>As we await the enrollment, analysis, and results of the START study — which is randomizing patients with CD4>500 to start HIV therapy \u00a0vs waiting until the CD4 falls to 350 — much of the research on “when to start” ART in patients with high CD4’s comes from observational studies. Several have already been published (NA-ACCORD<\/a>, ART-CC<\/a>, CAUSAL<\/a>), but one limitation of each of them is that none could accurately assess duration of HIV infection.<\/p>\n

Enter “CASCADE<\/a>“, or “Concerted Action on SeroConversion to AIDS and Death in Europe”. CASCADE includes patients from Europe, Australia, and Canada only if they have a defined date of HIV acquisition, thereby limiting effects of lead-time bias. In order to get at the when-to-start question, the investigators constructed something called “nested subcohorts” between 1996 and 2009, comparing the outcomes of those who started ART vs. those who didn’t.<\/p>\n

The results? Out of 9,455 patients, starting ART (vs deferring) was associated with a lower risk of developing AIDS or death for those with a CD4 cell count < 500 — but not for those who started between 500-799. An interesting aspect of this study is that they were able to calculate a “number needed to treat” (NNT) to prevent progression. Over 3 years of follow-up, 21 and 34 patients would need to start treatment to prevent one patient from progressing to AIDS or death in those with CD4s between 200-349 and 350-499 respectively.<\/p>\n

Usual caveats of observational studies apply — most notably that no such study can control for all factors between those who started ART vs those who didn’t that would influence outcome — but the results are helpful nonetheless, as the benefits of therapy before<\/em> the CD4 cell count falls to < 350 shown here have been consistently seen in multiple studies. Furthermore, the NNT data to prevent AIDS or death — 34 for CD4 between 350-499 — place the benefits of treating these patients as even greater than what we accomplish with statin therapy for hypercholesterolemia to prevent MIs<\/a>, which is estimated as 40-70.<\/p>\n

Bottom line: \u00a0Treating patients with CD4 350-500 and no symptoms may not be as exciting giving ART to someone with advanced HIV disease, but it sure makes good clinical sense.<\/p>\n","protected":false},"excerpt":{"rendered":"

As we await the enrollment, analysis, and results of the START study — which is randomizing patients with CD4>500 to start HIV therapy \u00a0vs waiting until the CD4 falls to 350 — much of the research on “when to start” ART in patients with high CD4’s comes from observational studies. Several have already been published […]<\/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":[77,83,423,992],"class_list":["post-1984","post","type-post","status-publish","format-standard","hentry","category-health-care","category-hiv","category-patient-care","category-research","tag-antiretroviral-therapy","tag-art","tag-hiv","tag-when-to-start"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/1984","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=1984"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/1984\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=1984"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=1984"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=1984"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}