{"id":32209,"date":"2017-08-10T12:19:20","date_gmt":"2017-08-10T12:19:20","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=32209"},"modified":"2017-08-15T08:10:32","modified_gmt":"2017-08-15T08:10:32","slug":"doravirine3tctdf-compared-to-efavirenzftctdf-as-first-line-art","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/32209","title":{"rendered":"Doravirine\/3TC\/TDF compared to efavirenz\/FTC\/TDF as first-line ART"},"content":{"rendered":"

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

Doravirine is a new once-daily NNRTI active against many first generation NNRTI resistant mutations, that is being developed by Merck in an FDC coformulated with generic lamivudine (3TC) and TDF<\/strong>.<\/p>\n

Results from a randomised phase 3 study comparing the doravirine\u00a0FDC to efavirenz\/FTC\/TDF (Atripla) in 728 treatment-naive participants were presented by Kathleen Squires from Thomas Jefferson University Hospital, Philadelphia.<\/p>\n

This is an ongoing, double-blind, placebo controlled non-inferiority study defined using a 10% boundary for the 95% confidence interval.<\/p>\n

Baseline characteristics included mean age 33 years, 85% male and 48% were white. Approximate mean (+\/\u2013SD) baseline CD4 and viral load were 420 (+\/\u2013 220) cells\/mm3<\/sup> and 4.4 (+\/\u2013 0.7) log copies\/mL respectively with approximately 12% having CD4 count <200 cells\/mm3<\/sup> and 20% having viral load >5 logs.<\/p>\n

At week-48, viral load <50 copies\/mL was reported for 84.3% (307\/364) vs 80.8% (294\/364) of the doravirine vs efavirenz groups respectively, (difference 3.5%, 95%CI [\u20132.0 to +9.0]). Viral suppression was similar between arms in participants with <100,000 and >100,000 copies\/mL (approximately 90% and 80% in each arm) and with baseline CD4 <200 and > 200 (approximately 69% vs 83% and 91% vs 90% in the doravirine vs efavirenz groups respectively). However, CD4 increases were similar between groups (+198 vs +188 cells\/mm3<\/sup>; difference +10, 95%CI: \u201316 to +36).<\/p>\n

There were slightly more protocol defined virological failures in the doravirine arm: n=22 (6%) vs n=14 (3%). Of these, 6 vs 4 were non-responders and 16 vs 10 involved viral rebound. Slightly fewer people in the doravirine arm discontinued for other reasons (n=35 vs 50).<\/p>\n

Of approximately 24 genotype tests in each arm, n=5 in each group had NRTI resistance and n=6 vs 12 people had NNRTI resistance).<\/p>\n

Doravirine was superior to efavirenz based on secondary endpoints CNS and lipid side effects.<\/p>\n

For example, dizziness (9% vs 37%, p<0.001), sleep disorders\/disturbances (12% vs 25%, p<0.001) and mood changes (4% vs 8%, p=0.03) were all significant. Similarly, fasting lipids included significantly reduced LDL (\u20131.6 vs +8.7 mg\/dL, p<0.0001), cholesterol and triglycerides for the doravirine group but higher HDL increases (+1.9 vs +8.5 mg\/dL) in the efavirenz group, and no data presented for HDL:TC ratio.<\/p>\n

The timeline for regulatory submission for doravirine in this FDC is unclear but marketing will depend on FDC patents for the generic TDF in different countries.<\/p>\n

These results support the doravirine FDC as a more tolerable alternative to efavirenz in treatment-naive participants.<\/p>\n

Reference:<\/p>\n

Squires KE et al. Fixed dose combination of doravirine\/lamivudine\/TDF is non-inferior to efavirenz\/emtricitabine\/TDF in treatment-na\u00efve adults with HIV-1 infection: week 48 results of the Phase 3 DRIVE-AHEAD study. IAS 2017, Paris. Late breaker oral abstract TUAB0104LB.
\nhttp:\/\/programme.ias2017.org\/Abstract\/Abstract\/5585<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Simon Collins, HIV i-Base Doravirine is a new once-daily NNRTI active against many first generation NNRTI resistant mutations, that is being developed by Merck in an FDC coformulated with generic lamivudine (3TC) and TDF. Results from a randomised phase 3 …<\/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":[243],"class_list":["post-32209","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","tag-ias-9-paris-2017"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/32209","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=32209"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/32209\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=32209"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=32209"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=32209"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}