{"id":36443,"date":"2019-07-24T15:38:24","date_gmt":"2019-07-24T15:38:24","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=36443"},"modified":"2020-02-11T12:09:45","modified_gmt":"2020-02-11T12:09:45","slug":"dual-therapy-with-islatravir-mk-8591-plus-doravirine-24-week-results-as-switch-strategy","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/36443","title":{"rendered":"Dual therapy with islatravir (MK-8591) plus doravirine: 24 week results as switch strategy"},"content":{"rendered":"

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

A late-breaking oral abstract at <\/b>IAS 2019 included the first results of a new dual therapy of the investigational NRTTI islatravir plus the NNRTI doravirine, compared to triple therapy with additional lamivudine (3TC). [1]<\/strong><\/p>\n

This was part of a phase 2b study for treatment na\u00efve participants who initiated ART with islatravir, doravirine and 3TC and who switched to dual ART at week 24 if viral load was undetectable (<50 copies\/mL). Participants taking longer than 24 weeks were able to switch when then did become undetectable. Week 24 results were already presented at IAS 2019 and reported separately. [2, 3]<\/p>\n

This was a randomised, double-blind, comparator-controlled, dose-ranging trial (using 0.25 mg, 0.75 mg or 2.25 mg once-daily doses of islatravir). This compound has a long intracellular half-life ~120 hours with potential for weekly and perhaps monthly dosing.<\/p>\n

Primary efficacy endpoints included the overall proportion of participants at week 48 with viral load < 50 copies\/mL by FDA snapshot analysis. The results at 48 weeks (following 24 weeks on dual ART) were presented by Jean-Michel Molina from St Louis Hospital, Paris.<\/p>\n

Baseline characteristics included mean age 31 years, 93% male. Mean CD4 count was 492 cells\/mm3<\/sup> (SD: 188) and 22% had viral load >100,000 copies\/mL.\u00a0Race included 76% white and 20% black but the study also referred to approximately half the participants being Hispanic or Latin American. Approximately 40% were treated in sites in North America, 30% in South American and 25% in Europe.<\/p>\n

At week 48, five participants in the islatravir arms (4 rebound, 1 non-response) vs one in the control arm (viral rebound) had viral load levels that were >50 copies\/mL. However, no participants had viral load rebound >200 copies\/mL and all were reported as being <80 copies\/mL. This was below the threshold to test for drug resistance and no new drug resistance was reported. Mean CD4 increases were similar in all groups.<\/p>\n

Tolerability was generally good. Drug-related AEs were reported less frequently for the combined dual therapy arms compared to triple drug control group (7.8% vs 19.4%).<\/p>\n

From week-48 all participants in the islatravir groups were changed to the 0.75 mg dose (for follow up until week-96) \u2013 although the dose to take forward into phase 3 studies has not yet been announced.<\/p>\n

The study concluded that dual therapy would continue to be studied.<\/p>\n

Table 1: Viral load responses after week 48: dual ART for 24 weeks,<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n
<\/td>\nISL 0.25mg + DOR<\/td>\nISL 0.75 mg + DOR<\/td>\nISL 2.25 mg + DOR<\/td>\ndoravirine
\n\/3TC\/TDF<\/td>\n<\/tr>\n
\u00a0n<\/td>\n29<\/td>\n30<\/td>\n31<\/td>\n31<\/td>\n<\/tr>\n
d\/c before wk 24<\/td>\n0<\/td>\n0<\/td>\n4<\/td>\n3<\/td>\n<\/tr>\n
d\/c wk 24-48<\/td>\n2<\/td>\n1<\/td>\n3<\/td>\n2<\/td>\n<\/tr>\n
<50 c\/mL wk 48<\/td>\n89% (26\/29)<\/td>\n90% (27\/30<\/td>\n77% (24\/31)<\/td>\n84% (26\/31)<\/td>\n<\/tr>\n
> 50 c\/mL\u00a0wk 48<\/td>\n7% (2\/29)<\/td>\n7% (2\/30)<\/td>\n13% (4\/31)<\/td>\n7% (2\/31)<\/td>\n<\/tr>\n
No data<\/td>\n3% (1\/29)<\/td>\n3% (1\/30)<\/td>\n10% (3\/31)<\/td>\n10% (3\/31)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

References<\/p>\n

    \n
  1. MolinaJ-M et al. MK-8591 at doses of 0.25 to 2.25 mg QD, in combination with doravirine establishes and maintains viral suppression through 48 weeks in treatment-na\u00efve adults with HIV-1 infection.10th IAS Conference on HIV Science (IAS 2019), 21-24 July 2019, Mexico City. Late-breaker oral abstract WEAB0402LB.
    \nhttp:\/\/programme.ias2019.org\/Abstract\/Abstract\/4789<\/a><\/li>\n
  2. MolinaJ-M et al. Tolerability, safety and efficacy of MK-8591 at doses of 0.25 to 2.25 mg QD, in combination with doravirine and lamivudine through 24 weeks in treatment-na\u00efve adults with HIV-1 infection. 10th IAS Conference on HIV Science (IAS 2019), 21-24 July 2019, Mexico City. Late breaker post abstract LBPED46.
    \n    http:\/\/programme.ias2019.org\/Abstract\/Abstract\/4694<\/a><\/li>\n
  3. Collins S.Islatravir (MK-8591) in new fixed dose combination (FDC) with doravirine plus lamivudine: 24 week results. HTB July 2019.
    \n    https:\/\/i-base.info\/htb\/36398<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base A late-breaking oral abstract at IAS 2019 included the first results of a new dual therapy of the investigational NRTTI islatravir plus the NNRTI doravirine, compared to triple therapy with additional lamivudine (3TC). [1] This was …<\/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":[273],"class_list":["post-36443","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-ias-10-mexico-city-2019"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/36443","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=36443"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/36443\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=36443"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=36443"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=36443"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}