{"id":35937,"date":"2019-03-28T09:49:05","date_gmt":"2019-03-28T09:49:05","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=35937"},"modified":"2019-03-29T15:11:15","modified_gmt":"2019-03-29T15:11:15","slug":"maturation-inhibitor-gsk-232-reduces-viral-load-by-1-5-log-at-day-10","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/35937","title":{"rendered":"Maturation inhibitor GSK’232 reduces viral load by \u20131.5 log at day 10"},"content":{"rendered":"

\"\"Simon Collins, HIV i-Base<\/span><\/strong><\/p>\n

Results from a 10-day phase 2a dose-finding study for <\/span><\/b>GSK2838232 (GSK’232) \u2013 a maturation inhibitor in development at GSK \u2013\u00a0were presented by Edwin DeJesus from Orlando Immunology Centre.<\/span><\/b><\/p>\n

Maturation inhibitors bind to gag protein to target a late-stage of viral lifecycle and the development of two previous compounds in this class were stopped due to limited activity due to commonly occurring polymorphisms (beviramat) and side effects (BMS-955176).<\/span><\/p>\n

The new GSK compound has good in vitro potency, minimal protein binding and broad-spectrum activity (including against polymorphisms associated with beviramat).<\/span><\/p>\n

GSK’232 was given once-daily with cobicistat boosting. Doses in this two-part study were 20 mg, 50 mg, 100 mg and 200 mg – each given with cobicistat 150 mg. The 100 mg dose was run as the first part of this study.<\/span><\/p>\n

Approximate baseline characteristics of the 33 participants (largely young white men) included mean CD4 and viral load of 540 cells\/mm3\u00a0<\/sup>and 58,000 copies\/mL (range: 1300 to 363,000), respectively.<\/span><\/p>\n

Mean viral load decline at day 10 was \u20131.5 log copies\/mL in the 200 mg arm and 1.2 log copes\/mL on the 50 mg and 100 mg arms, sustained for several days before returning towards baseline over the following 10 days.<\/span><\/p>\n

Steady state was reached by day 8 and most PK parameters (AUC, Cmax and C trough) showed broadly dose-proportional responses. <\/span><\/p>\n

Resistance results at days 1 and 11 were available for 28\/33 participants. Two participants (one in the 50 mg and one in the 100 mg arms) had genotypic changes at A364A\/W in gag, which phenotypic resistance to GSK’232 detected at day 11 in the 50 mg participant.<\/span><\/p>\n

Reduced baseline sensitivity to GSK’232 in another participant in the 50 mg arm only produced a viral load reduction of 0.17 log copies\/mL.<\/span><\/p>\n

Tolerability was good with no pattern form mild\/moderate side effects or dose relationship, with no serious events and no discontinuations. There were no grade 3\/4 lab abnormalities or clinically significant ECG abnormalities.<\/span><\/p>\n

Reference<\/span><\/p>\n

DeJesus E et al. <\/span>A phase IIa study of novel maturation inhibitor GSK2838232 in HIV patients. Conference on Retroviruses and Opportunistic Infections (CROI), 4-7 March 2019, Seattle. <\/span>Oral abstract 142.
\nhttp:\/\/www.croiconference.org\/sessions\/phase-iia-study-novel-maturation-inhibitor-gsk2838232-hiv-patients<\/a> (abstract)
\n<\/span>http:\/\/www.croiwebcasts.org\/console\/player\/41311<\/a> (webcast)<\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base Results from a 10-day phase 2a dose-finding study for GSK2838232 (GSK’232) \u2013 a maturation inhibitor in development at GSK \u2013\u00a0were presented by Edwin DeJesus from Orlando Immunology Centre. Maturation inhibitors bind to gag protein to target …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3],"tags":[264],"class_list":["post-35937","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-croi-2019"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35937","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=35937"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35937\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=35937"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=35937"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=35937"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}