{"id":7234,"date":"2005-07-14T09:05:26","date_gmt":"2005-07-14T08:05:26","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=7234"},"modified":"2014-05-21T17:23:26","modified_gmt":"2014-05-21T17:23:26","slug":"predicting-clinical-responses-to-ddi-from-genotypic-resistance","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/7234","title":{"rendered":"Predicting clinical responses to ddI from genotypic resistance"},"content":{"rendered":"<p><strong>Simon Collins, HIV i-Base<\/strong><\/p>\n<p><strong>Shulman and colleagues addressed the difficulty of interpreting resistance to ddI, by analysing stored samples from 444 treatment-experienced patients in three ACTG studies (359, 368 and 398) to test the results against responses to ddI monotherapy in ACTG 175 and ACTG 309.<\/strong><\/p>\n<p>Paired genotype-phenotype samples were compared to consensus RT and compared with treatment response. 16\/444 had &gt;4 fold change (all with either Q151M or substitutions at 69) and these samples were excused from the analysis.<\/p>\n<p>In the remaining 428 cases, 20 codons with P&lt;0.01 in the univariate analysis were used in stepwise regression modeling. This resulted in nine codons in the final multivariate model: 184, 215, 43, 67, 74, 223, 210, and 75 were associated with increased resistance (all p&lt;0.001) while 83 was associated with decreased resistance.<\/p>\n<p>The predictability of these mutations was tested against 52 genotype and 46 phenotype samples from ACTG 175 and ACTG 307. The resulting resistance score (total score = 184 + 215 + 43 + 67 + 74 + 223 + 210 + 75 \u0096 83) had a strong correlation between with ddI-fold sensitivity change (Spearman r=0.67 (P&lt;0.0001).<\/p>\n<p>This fitted more accurately than the Jaguar score (M41L + L74V + D67N + K219Q\/E + T215Y\/F + T69D \u0096 K70R \u0096 M184V) which is based on 4 week virological response to ddI in patients with a relatively high CD4 count, and correlated with fold-change, r=0.38, P&lt;0.0001.<\/p>\n<p>The low phenotypic change associated with loss of activity with ddI makes predicting response from genotypic results a difficult challenge, for which there is certainly a clinical need. An important suggestion from the audience, similar to other studies, was that cooperation between the researchers in ths study and those involved Jaguar should usefully now cross-validate each set of results.<\/p>\n<p>Reference:<\/p>\n<p>Shulman N, Bosch R, Fiscus S et al. Mutations associated with didanosine resistance determined from 444 matched genotype-phenotype pairs. 14th International HIV Drug Resistance Workshop (14th IHDRW), 7-11 June 2005, Quebec City, Canada.\u00a0Abstract 49. Antiviral Therapy 2005; 10:S54<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Simon Collins, HIV i-Base Shulman and colleagues addressed the difficulty of interpreting resistance to ddI, by analysing stored samples from 444 treatment-experienced patients in three ACTG studies (359, 368 and 398) to test the results against responses to ddI monotherapy &hellip;<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,36],"tags":[111],"class_list":["post-7234","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-drug-resistance","tag-idrw-14th-2005"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7234","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=7234"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7234\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=7234"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=7234"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=7234"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}