{"id":1777,"date":"2008-02-01T09:02:16","date_gmt":"2008-02-01T08:02:16","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=1777"},"modified":"2013-08-30T11:10:40","modified_gmt":"2013-08-30T11:10:40","slug":"background-drugs-and-low-maraviroc-levels-explain-resistance-in-motivate-studies","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/1777","title":{"rendered":"Background drugs and low maraviroc levels explain resistance in Motivate studies"},"content":{"rendered":"

Mark Mascolini, for NATAP<\/strong><\/p>\n

Having only one or no active drugs in the background regimen explained emergence of virus resistant to the CCR5 antagonist maraviroc in the salvage trials MOTIVATE 1 and 2, according to new work by Pfizer researchers<\/strong> [1]. All 4 people in whom maraviroc-resistant virus emerged during the study had low concentrations of the drug.<\/strong><\/p>\n

Thirty-eight of 267 enrollees in the placebo-controlled MOTIVATE trials met criteria for virologic failure with R5-using virus, including 12 in the maraviroc group–7 taking maraviroc once daily and 5 taking maraviroc twice daily. (Maraviroc is licensed for twice-daily dosing.) In 4 of the 12 people with maraviroc failure, Pfizer detected emergence of mutations in the gene that codes for the V3 loop of HIV\u0092s envelope protein gp120 [2].<\/p>\n

These mutations differed from person to person, but all 4 people still had R5-using HIV when their regimen failed. Three of the four were taking maraviroc once daily. Viral loads before these 4 people started maraviroc ranged from 4.87 to 5.64 log copies\/mL, and their CD4 counts ranged from 4 to 177.<\/p>\n

To get a better handle on how resistance to maraviroc evolves, the Pfizer team determined viral susceptibility to maraviroc and background regimen drugs in these 4 patients before they started their maraviroc salvage regimen and when that regimen failed. They also measured concentrations of maraviroc in samples collected from patients during the trial.<\/p>\n

Maraviroc resistance mutations emerged in 3 people who had no active drugs in their background regimen, according to prestudy resistance tests. The other person in whom maraviroc-related mutations evolved during failure had only one active drug in the background regimen–enfuvirtide–and HIV became resistant to that drug during the trial.<\/p>\n

All 4 people in whom maraviroc failed with resistance mutations had low concentrations of the CCR5 antagonist during the study. Two people taking once-daily maraviroc and 1 taking twice-daily maraviroc had average concentrations from 93 to 98 ng\/mL–just below the target minimum concentration of 100 ng\/mL. The fourth person, who took maraviroc once daily, averaged only 44 ng\/mL.<\/p>\n

Time to treatment failure measured 49 days, 58 days, and 169 days in the 3 people who had no active drugs except maraviroc in their salvage regimen. In the 1 person with active enfuvirtide in the background regimen, times to treatment failure measured 114 days.<\/p>\n

Among the 8 people in whom maraviroc failed with no evidence of resistance mutations, 3 had no active drugs in their background regimen, 2 had one active drug (amprenavir or abacavir), 2 had two active drugs (3TC\/abacavir or tenofovir\/atazanavir\/ritonavir), and 1 had three active drugs (3TC\/abacavir plus lopinavir\/ritonavir). Maraviroc concentrations were good in 2 of these 8 (205 and 268 ng\/mL), marginally low in another 2, one of whom temporarily discontinued maraviroc (97 and 94 ng\/mL), and very low in the other 4 (1 to 50 ng\/mL).<\/p>\n

References:<\/p>\n

    \n
  1. Mori J, Lewis M, Simpson P, et al. Characterization of maraviroc resistance in patients failing treatment with CCR5-tropic virus in MOTIVATE 1 and 2. Targeting HIV Entry: 3rd International Workshop. December 7-9, 2007. Washington, DC. Abstract 21.<\/li>\n
  2. Mori J, Mosley M, Lewis M, et al. Characterization of maraviroc resistance in patients failing treatment with CCR5-tropic virus in MOTIVATE 1 and MOTIVATE 2. Antiviral Therapy 2007;12:S12. Abstract 10.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Mark Mascolini, for NATAP Having only one or no active drugs in the background regimen explained emergence of virus resistant to the CCR5 antagonist maraviroc in the salvage trials MOTIVATE 1 and 2, according to new work by Pfizer researchers …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,36],"tags":[88],"class_list":["post-1777","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-drug-resistance","tag-hiv-entry-workshop-3rd-2007"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1777","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=1777"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1777\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=1777"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=1777"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=1777"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}