{"id":32207,"date":"2017-08-10T12:18:05","date_gmt":"2017-08-10T12:18:05","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=32207"},"modified":"2017-08-15T08:12:35","modified_gmt":"2017-08-15T08:12:35","slug":"reduced-dose-darunavir-is-safe-and-effective-in-switch-study","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/32207","title":{"rendered":"Reduced-dose darunavir is safe and effective in switch study"},"content":{"rendered":"

\"IASPolly Clayden HIV i-Base<\/strong><\/p>\n

A 400\/100 mg once-daily darunavir\/ritonavir (DRV\/r) dose plus two NRTIs maintained virologic efficacy through 48 weeks in participants previously suppressed with DRV\/r 800\/100 mg.<\/strong> [1]<\/p>\n

These data from the ANRS-165 Darulight study were shown at IAS2017.<\/p>\n

Darulight was a multicentre, phase 2, single arm, open label study in stable participants with viral load <50 copies\/mL who had received DRV\/r 800\/100 mg for at least 12 months.<\/p>\n

Of 100 participants enrolled in the study, 95 were included in the modified intent to treat analysis.<\/p>\n

A minimum of 94 participants were needed to detect a difference in success rate from 80% to 90% with 85% power.<\/p>\n

Participants were a median age of 43 years and 78% were male. They had received ART for a median of 46 months, and had a median CD4 count of 633 cells\/mm3<\/sup> and duration of viral load <50 copies\/mL of 35 months. The majority (76%) received a TDF\/FTC backbone and the remainder ABC\/3TC.<\/p>\n

At 48 weeks 87 of 95 participants had viral load <50 copies\/mL: 91.6% (95% CI 84.1 to 96.3), p<0.001. Of the remaining 8 participants: 2 changed DRV dose without virological failure; 6 had viral load >50 copies\/mL (2 >200 copies\/mL).<\/p>\n

The only risk factor for viral load >50 copies\/mL was baseline peak viral load >threshold: OR 4.76 (95% CI 1.47 to 15.4), p=0.009.<\/p>\n

Nine participants had serious adverse advents, none led to treatment discontinuation.<\/p>\n

A pharmacokinetic sub study of Darulight conducted in 15 men found total and unbound blood and seminal plasma exposure of DRV to be not significantly different between both doses, despite 50% dose reduction. [2]<\/p>\n

Unexpectedly total blood plasma exposure of ritonavir trended to be higher in 400\/100mg once-daily, than in 800\/100mg once-daily (p=0.09) due to a change in the inducer\/inhibitor balance between DRV and RTV.<\/p>\n

comment<\/h3>\n

DRV has long been a candidate for dose optimisation and these data support further investigation.<\/strong><\/p>\n

A DRV\/r 400\/100 mg switch trial in South Africa is currently enrolling participants, stable on boosted lopinavir-based second-line.<\/strong> [3]<\/p>\n

And plans for phase 2 and 3 studies in unsuppressed participants are underway. <\/strong><\/p>\n

Fit for Purpose July 2017 gives more details<\/strong> [4]<\/p>\n

References:<\/p>\n

    \n
  1. Molina JM et al. Efficacy and safety of 400 mg darunavir\/100 mg ritonavir with TDF\/FTC or ABC\/3TC in virologically suppressed HIV-1 infected adults: an open-label study \u2013 ANRS-165 Darulight. IAS 2017. 23\u201326 July 2017. Paris. \u00a0Poster abstract MOPEB0313.
    \nhttp:\/\/programme.ias2017.org\/Abstract\/Abstract\/1075<\/a><\/li>\n
  2. L\u00ea MP et al. Pharmacokinetic modelling of darunavir\/ritonavir dose reduction (800\/100 mg to 400\/100mg once daily) containing regimen in virologically suppressed HIV-infected patients as maintenance treatment: ANRS-165 DARULIGHT sub-study. Poster abstract MOPEB0329.
    \n    http:\/\/programme.ias2017.org\/Abstract\/Abstract\/1586<\/a><\/li>\n
  3. US National Institutes of Health. Evaluation of\u00a0low-dose darunavir\u00a0in a switch study (DRV).
    \n    https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02671383<\/a><\/li>\n
  4. Clayden P. Antiretroviral treatment optimisation for adults and children. Fit for Purpose. 24 July 2017.
    \n    https:\/\/i-base.info\/htb\/32022<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Polly Clayden HIV i-Base A 400\/100 mg once-daily darunavir\/ritonavir (DRV\/r) dose plus two NRTIs maintained virologic efficacy through 48 weeks in participants previously suppressed with DRV\/r 800\/100 mg. [1] These data from the ANRS-165 Darulight study were shown at IAS2017. …<\/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-32207","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\/32207","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=32207"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/32207\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=32207"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=32207"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=32207"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}