{"id":35248,"date":"2018-11-13T11:27:53","date_gmt":"2018-11-13T11:27:53","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=35248"},"modified":"2018-11-13T16:14:52","modified_gmt":"2018-11-13T16:14:52","slug":"dual-bnab-maintains-viral-suppression-for-median-21-weeks-off-art","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/35248","title":{"rendered":"Dual bNAb maintains viral suppression for median 21 weeks off-ART"},"content":{"rendered":"

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

In the first presentation in a session at R4P2018 looking at using bNAbs for prevention, <\/span><\/b>Pilar Mendoza from the Rockefeller University presented results on the impact of a combination of two antibodies in HIV positive people on ART who then took an analytic treatment interruption (ATI). [1]<\/span><\/b><\/p>\n

The two bNAbs, 3BNC117 and 10-1074, target non-overlapping epitopes and provide broader coverage. \u00a0All\u00a011 participants were initially screened for sensitivity to both antibodies (there was an approximate 50% rate of failing screening) and were on effective ART. <\/span><\/p>\n

ART was stopped two days after the first dual infusion, with additional infusions at weeks 3 and 6 when off ART.<\/span><\/p>\n

The reservoir was measured at the first infusion and at 12 weeks (when suppressions was still expected) and the criteria to restart ART was two consecutive viral load results >200 copies\/mL or at 30 weeks, whichever was sooner.<\/span><\/p>\n

Viral suppression using the dual bNAbs resulted in median 21 weeks to viral rebound >200 copies\/mL, which was significantly longer compared to historical controls or previous single bNAb studies (p <0.0003). Two participants were still virally suppressed at week 30.<\/span><\/p>\n

However, 2\/11 participants were later found to have preexisting bNAb resistance in the viral reservoir that was not detected at baseline, and both responded with similar early viral rebound to monotherapy studies.<\/span><\/p>\n

Analysis of the time to rebound in the 9\/11 sensitive participants showed this closely linked to when plasma levels of 3BNC117 fell below estimated therapeutic concentrations of 10 ug\/mL, leaving a window of monotherapy to 10-1074 due to it’s longer half-life. This also meant that rebound virus tended to show resistance to 10-1074. <\/span><\/p>\n

Some participants also rebounded after both antibodies were cleared. No cases of double resistance were reported.<\/span><\/p>\n

No reduction in the viral reservoir was seen between baseline and week 12.<\/span><\/p>\n

Previous studies using 3BNC117 monotherapy delayed viral rebound by approximately nine weeks.\u00a0<\/span><\/p>\n

comment<\/span><\/h2>\n

These tentative results show an exciting potential for combination bNAbs therapy to maintain viral suppression off-ART.<\/span><\/strong><\/p>\n

However, the rapid rebound with antibody resistance during periods of effective monotherapy is an important caution for future research.<\/span><\/strong><\/p>\n

This also creates a challenge for considering pharmacokinetic profiles of different molecules when used in combinations.<\/span><\/strong><\/p>\n

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

    \n
  1. Mendoza P et al.\u00a0Combination of HIV-1 antibodies 3BNC117 and 10-1074 delays viral rebound during treatment interruption. R4P2018, 21-25 October 2018, Oral abstract\u00a0OA08.01.
    \n<\/span>http:\/\/webcasts.hivr4p.org\/console\/player\/40352<\/a> (webcast)<\/span><\/li>\n<\/ol>\n

    \u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base In the first presentation in a session at R4P2018 looking at using bNAbs for prevention, Pilar Mendoza from the Rockefeller University presented results on the impact of a combination of two antibodies in HIV positive people …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3,41],"tags":[259],"class_list":["post-35248","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","category-treatment-strategies","tag-r4p-2018-madrid"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35248","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=35248"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35248\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=35248"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=35248"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=35248"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}