{"id":2962,"date":"2006-10-07T13:51:24","date_gmt":"2006-10-07T12:51:24","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=2962"},"modified":"2013-12-06T15:49:49","modified_gmt":"2013-12-06T15:49:49","slug":"nucleoside-inhibitor-mk-0608-mediates-suppression-of-hcv-replication-for-30-days-in-chronically-infected-chimpanzees","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/2962","title":{"rendered":"Nucleoside inhibitor MK-0608 mediates suppression of HCV replication for >30 days in chronically infected chimpanzees"},"content":{"rendered":"<p><strong>Jules Levin, natap.org<\/strong><\/p>\n<p><strong>There are 3 HCV polymerase inhibitors in patient studies now: HCV-796; R1626; NM283. HCV-796 &amp; R1626 showed 1.2 o 1.4 log viral load reductions in 10 day studies. And there are 2 HCV protease inhibitors in patients studies: VX-950, which showed 4.4 log reductions in 14 day study in viral load, and SCH503034 which showed about 1.8 logs viral load reduction in 14 day study.<\/strong><\/p>\n<p>David Olsen et al from Merck reported in a poster on this last day at ICAAC new study results of a study reporting the effect of a new HCV polymerase inhibitor MK-0608 in chimpanzees. The first presentation of MK-0608 was at the HIV Drug Resistance Workshop in the Summer of 2006 where a 5.7 log reduction was seen in chimps after 7 days, and with one dose three logs reduction was seen.<\/p>\n<p>The results reported an average reduction of 4.7 logs HCV RNA for 4 chimps who were treated. Three of 4 chimps had undetectable HCV RNA with a sensitive assay. But the baseline viral loads were lower for these 3 chimps than the chimp that saw a 5.7 log viral load reduction reported at the Resistance Workshop. Of note, until now we have seen these types of deep HCV RNA reductions only in HCV protease inhibitors.<\/p>\n<p>Once-daily dosing of MK-0608 for 37 days in HCV chronically infected resulted in a rapid decrease in plasma viral RNA to below the limit of quantification (20 IU\/ml) in 3 of 4 animals in less than 10 days.<\/p>\n<p>Continued administration for up to 37 days resulted in sustained suppression of viral load to levels below detection that remained undetectable throughout the dosing period.<\/p>\n<p>Viral load in the fourth chimpanzee (starting titer &gt;106 IU\/mL) decreased by 4.7 logs during dosing without the selection of resistant virus. All animals experienced a rebound in viral load upon cessation of dosing.<\/p>\n<p>Author conclusions included that IV and oral dosing of MK-0608 to HCV infected chimpanzees resulted in significant reductions in viral load: &gt;5 log reduction in viral load (mg\/kg IV), no rebound during dosing and a delay in rebound after end of extended dosing The resistance genotype included mutations at amino acid 282, with reversion back to wild-type sequence suggesting this mutation impacts on viral fitness.<\/p>\n<p class=\"ref\">Reference:<\/p>\n<p class=\"ref\">Olsen DB, Davies M, Handt L et al. The nucleoside inhibitor MK-0608 mediates suppression of HCV replication for &gt;30 days in chronically infected chimpanzees. 46th ICAAC, Toronto 2006. Abstract V-1914a.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Jules Levin, natap.org There are 3 HCV polymerase inhibitors in patient studies now: HCV-796; R1626; NM283. HCV-796 &amp; R1626 showed 1.2 o 1.4 log viral load reductions in 10 day studies. And there are 2 HCV protease inhibitors in patients &hellip;<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,24],"tags":[101],"class_list":["post-2962","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-hepatitis-coinfection","tag-icaac-46th-2006"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/2962","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=2962"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/2962\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=2962"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=2962"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=2962"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}