{"id":43149,"date":"2022-07-01T07:42:36","date_gmt":"2022-07-01T07:42:36","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=43149"},"modified":"2022-07-01T08:24:22","modified_gmt":"2022-07-01T08:24:22","slug":"combination-bnabs-sustain-viral-suppression-for-50-weeks-phase-1-results","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/43149","title":{"rendered":"Combination bNAb’s sustain viral suppression for 40 weeks: phase 1 results"},"content":{"rendered":"
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Kirk Taylor, HIV i-Base<\/strong><\/p>\n<\/div>\n

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A combination of two broadly-neutralising antibodies (bNAbs) \u2013 3BNC117 and 10-1074 \u2013 maintained<\/span> undetectable viral load after interrupting ART for over 40 weeks. [1] <\/span><\/strong><\/p>\n<\/div>\n

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This paper was published in 1 June 2022 edition of Nature reported on two studies run from September 2018 to January 2021. The first was a randomised placebo-controlled study in 14 participants already suppressed on ART that had been started during acute infection. A second open-label study was in five treatment naive participants. Neither study screened participants for sensitivity to the bNAbs.<\/span><\/p>\n<\/div>\n

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Participants were randomised 1:1 to bNAb’s or placebo (Group 1); or enrolled in the open label study (Groups 2). All participants were male, 12\/19 were white and median age was 39 (range: 27 to 57).<\/span><\/p>\n<\/div>\n

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Median baseline CD4 counts were 799 cells\/mm3<\/sup> (range: 543 to 1,177) vs 612 cells\/mm3<\/sup> (426 to 832) in the active vs placebo arms; and 640 cells\/mm3\u00a0<\/sup>(540 to 1,1011) in Group 2 where viral load ranged from 200 to 5,000 copies\/mL<\/span><\/p>\n<\/div>\n

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Participants received bNAbs across 8 infusions: twice in month 1 and then monthly for 6 months, ART was stopped three days after the first infusion. <\/span><\/p>\n<\/div>\n

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Those receiving bNAbs in group 1 were off ART for a median of 39.6 weeks (range 9.9 to 49.6). Median viral suppression for 40% of group 2 participants was 41.7 weeks. In Group 1, ART was restarted for 6 out of 7 participants in the placebo group before week 28 (median 9.4 weeks; range 5.3 to 26).<\/span><\/p>\n<\/div>\n

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L<\/span>ongitudinal measurements did not indicate a reduction HIV reservoir in participants that received bNAbs. Participant CD4 counts did however remain stable across the study period.<\/p>\n<\/div>\n

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comment<\/span><\/h3>\n<\/div>\n
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Although ART is highly effective, stopping treatment usually leads to rapid viral rebound often within two weeks . Early results using bNAbs have included the potential to maintain viral suppression off-ART. <\/span><\/strong><\/p>\n<\/div>\n

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3BNC117 and 10-1074 are promising bNAb therapies that target the CD4 binding site and V3 loop of the HIV, respectively. Previous studies have also reported sustained suppression off ART. [2, 3]<\/span><\/strong><\/p>\n<\/div>\n

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Of note, both antibodies are older formulations, with more recent LC variants now providing significantly longer half-lives, with a single infusion expected to last more than 16 weeks.<\/span><\/strong><\/p>\n<\/div>\n

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The long-acting formulations of these bNAbs are included in the UK RIO study that is currently recruiting in London and Brighton and shortly begin in Manchester. [4]<\/span><\/strong><\/p>\n<\/div>\n

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References<\/span><\/p>\n<\/div>\n

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  1. Sneller MC et al. Combination anti-HIV antibodies provide sustained virological suppression. Nature. https:\/\/doi.org\/10.1038\/s41586-022-04797-9\u00a0 (01 Jun 2022).
    \n<\/span>https:\/\/www.nature.com\/articles\/s41586-022-04797-9<\/a><\/li>\n
  2. Mendoza P et al. Combination therapy with anti HIV-1 antibodies maintains viral suppression. Nature. https:\/\/doi.org\/10.1038\/s41586-018-0531-2 (26 Sep 2018)
    \n    https:\/\/www.nature.com\/articles\/s41586-018-0531-2\u00a0<\/a><\/li>\n
  3. Jefferys R. CROI 2022: targeting reservoir with ART + bNAb 3BNC117 + romidepsin maintained undetectable viral load off-ART for 3.7 years in one case. (HTB 01 Mar 2022).
    \n    https:\/\/i-base.info\/HTB\/42209<\/a><\/li>\n
  4. The RIO study.
    \n    https:\/\/riotrial.org<\/a><\/li>\n<\/ol>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

    Kirk Taylor, HIV i-Base A combination of two broadly-neutralising antibodies (bNAbs) \u2013 3BNC117 and 10-1074 \u2013 maintained undetectable viral load after interrupting ART for over 40 weeks. [1] This paper was published in 1 June 2022 edition of Nature reported …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,20],"tags":[],"class_list":["post-43149","post","type-post","status-publish","format-standard","hentry","category-antiretrovirals","category-cure-research"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/43149","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=43149"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/43149\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=43149"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=43149"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=43149"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}