{"id":34358,"date":"2018-06-29T08:34:00","date_gmt":"2018-06-29T08:34:00","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=34358"},"modified":"2019-03-28T17:12:04","modified_gmt":"2019-03-28T17:12:04","slug":"reduced-exposure-to-elvitegravir-in-pregnancy-results-from-the-panna-network","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/34358","title":{"rendered":"Reduced exposure to elvitegravir in pregnancy: results from the PANNA Network \u00a0"},"content":{"rendered":"

Polly Clayden, HIV i-Base<\/strong><\/p>\n

Preliminary data from a small pharmacokinetic (PK) study suggests exposure to elvitegravir is lower during the third trimester of pregnancy than postpartum. [1] <\/strong><\/p>\n

These results are in line with those from IMPAACT and support caution for its initial use in pregnancy. [2, 3, 4]<\/p>\n

PANNA is an open-label, multi-centre, observational, phase 4 study in HIV positive pregnant women recruited in HIV treatment centres in Europe. The findings were presented at the 19th International Workshop on Clinical Pharmacology<\/p>\n

Participants receiving elvitegravir\/cobicistat 150\/150mg + 2 NRTIs (86% TDF\/FTC) once daily during pregnancy had intensive steady-state 24-hour PK-profiling in the third trimester and 5\u20137 weeks postpartum. Optional cord and matching maternal blood samples were taken at delivery. Seven participants with a median age of 32 years (range 25\u201340) years were included in the analysis.<\/p>\n

Geometric mean ratios of PK parameters during the third trimester\/postpartum were: 0.67 h*mg\/L (90% CI: 0.47 to 0.96) for AUC0-24; 0.79 mg\/L (90% CI: 0.61 to 1.02) for Cmax; 0.35 mg\/L (90% CI: 0.0.16 to 0.76) for Ctrough.<\/p>\n

Five out of seven participants had a sub-therapeutic Ctrough in the third trimester, one out of six postpartum. The median cord\/maternal elvitegravir plasma concentration ratio (n=4) was 0.87 mg\/L (range 0.3 to 1.2) \u2013 indicating substantial foetal exposure around delivery.<\/p>\n

During pregnancy 71% of the participants had sub-therapeutic Ctrough versus 17% postpartum.<\/p>\n

The investigators noted that cobicistat exposure was 56% lower during pregnancy, which might have led to less boosting, increased elvitegravir clearance and, in turn, lower exposure.<\/p>\n

Approaching delivery 6\/7 (86%) participants had viral load <50 copies\/mL; one participant had a viral load of 6363 copies\/mL six weeks before delivery.<\/p>\n

There were no serious adverse events or birth defects in this small study and all infants were HIV negative.<\/p>\n

comment<\/h3>\n

These PK results are similar to those presented previously by the IMPAACT Network, based on which, US DHHS perinatal guidelines do not recommend elvitegravir\/cobicistat for initial use in pregnancy.<\/strong><\/p>\n

The upcoming BHIVA guidelines will recommend that <\/strong>elvitegravir\/cobicistat may be continued with close monitoring if a woman receiving it with undetectable viral load becomes pregnant but not do recommend starting in pregnancy.<\/strong><\/p>\n

POSTSCRIPT: In March 2019 Gilead issue a Dear Doctor letter noting that elvitegravir\/cobicistat should not be continued during pregnancy and that women should be changed to an alternative combination.<\/strong><\/p>\n

References<\/p>\n

    \n
  1. Colbers A et al. Elvitegravir pharmacokinetics during pregnancy and postpartum.19th International Workshop on Clinical Pharmacology, 22\u201324 May 2018, Baltimore. Oral abstract 17.
    \n<\/strong>http:\/\/regist2.virology-education.com\/presentations\/2018\/Antiviralpk\/19_colbers.pdf<\/a>\u00a0(PDF)<\/li>\n
  2. Best B et al.Elvitegravir\/cobicistat pharmacokinetics in pregnancy and postpartum. CROI 2017. Seattle, Washington. February 13\u201316, 2017. Poster abstract 755.
    \n    http:\/\/www.croiconference.org\/sessions\/elvitegravircobicistat-pharmacokinetics-pregnancy-and-postpartum<\/a><\/li>\n
  3. US DHHS. Recommendations for the use of antiretroviral drugs in pregnant women with HIV infection and interventions to reduce perinatal HIV transmission in the United States. 30 May 2018.
    \n    https:\/\/aidsinfo.nih.gov\/guidelines\/html\/3\/perinatal\/224\/whats-new-in-the-guidelines<\/a><\/li>\n
  4. Clayden P. Key changes to upcoming UK HIV pregnancy guidelines (2018). HTB. 1 May 2018.
    \n    https:\/\/i-base.info\/htb\/34013<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Polly Clayden, HIV i-Base Preliminary data from a small pharmacokinetic (PK) study suggests exposure to elvitegravir is lower during the third trimester of pregnancy than postpartum. [1] These results are in line with those from IMPAACT and support caution for …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,35,34],"tags":[254],"class_list":["post-34358","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pmtct-and-maternal-health","category-pk-and-drug-interactions","tag-pk-workshop-2018"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/34358","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=34358"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/34358\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=34358"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=34358"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=34358"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}