{"id":32228,"date":"2017-08-10T12:14:04","date_gmt":"2017-08-10T12:14:04","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=32228"},"modified":"2017-08-15T08:23:10","modified_gmt":"2017-08-15T08:23:10","slug":"low-dose-efavirenz-efv400-can-be-used-in-pregnancy","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/32228","title":{"rendered":"Low dose efavirenz (EFV400) can be used during pregnancy"},"content":{"rendered":"

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

Results from a pharmacokinetic (PK) study of 400 mg efavirenz (EFV400) during\u00a0pregnancy, showed lower drug concentrations in the third trimester, compared with post-partum, but these were within adequate ranges described elsewhere. The findings were presented as a late breaker poster at IAS 2017.<\/strong> [1]<\/p>\n

WHO guidelines recommend EFV400 as alternative first-line drug, with a disclaimer that no data exist on its use at this dose during the third trimester of pregnancy.<\/p>\n

This study investigated the PK, efficacy and CYP2B6 pharmacogenetics of EFV400 in HIV positive women during third trimester (TT) and post-partum (PP). The aim was to provide data to support the removal of the WHO disclaimer to allow wider EFV400 first-line use.<\/p>\n

It was an open-label, multicentre study conducted in UK and Uganda in women receiving tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and EFV 600 mg with an undetectable viral load (<50 cells\/mm3), who switched to TDF\/FTC\/EFV400.<\/p>\n

The investigators evaluated weekly therapeutic drug monitoring (TDM) 10\u201314 hours post dose, steady-state PK profiles during TT and PP, safety, virologic efficacy and polymorphisms in CYP2B6 (516C>T and 938T>C).<\/p>\n

The primary endpoint was the comparison of EFV Ctrough TT vs PP using geometric mean ratios (GMR). A sample size of 25 provided at least 80% power to detect a 20% decrease in Ctrough during TT vs PP.<\/p>\n

The study enrolled 25 women of African origin: baseline median age and CD4 were 29 years (range 18 to 41) and 561 cells\/mm3 (range 152 to 882), respectively. All women had baseline viral load <50 copies\/mL at enrolment and remained undetectable throughout the study (there were only two viral load blips, both confirmed <50 copies\/mL, when repeated).<\/p>\n

All of the infants were HIV uninfected. No women were excluded because of low EFV400 TDM results (<800 ng\/mL in >3 consecutive visits).<\/p>\n

GMR (TT\/PP) of EFV400 Cmax, AUC, and C24trough were: 0.93 (90% CI 0.80 to 1.08), 0.84 (90% CI 0.72 to 0.99), 0.73 (90% CI 0.60 to 0.89).<\/p>\n

Of 25 women, 23 were carriers of the CYP2B6 516G allele and only two were slow metabolisers.<\/p>\n

EFV400 was well tolerated in pregnancy with no grade 3 or 4 laboratory abnormalities.<\/p>\n

Cmax, AUC, and Ctrough in TT were 7%, 27% and 26% lower compared with PP but within ranges previously reported for EFV600 during TT and those measured in ARV-naive patients receiving EFV400 in ENCORE1. [2, 3]<\/p>\n

All participants maintained a viral load <50 copies\/mL, suggesting that EFV400 can be used in pregnant HIV positive women.<\/p>\n

Comment<\/h3>\n

Like dolutegravir, EFV400 is an alternative option in 2016 WHO guidelines.<\/strong><\/p>\n

Evidence for efficacy in pregnancy at the lower dose (as described above) and with TB co-treatment (for which a PK study is ongoing) are needed for an unrestricted WHO recommendation.\u00a0<\/strong><\/p>\n

References:<\/p>\n

    \n
  1. Boffito M et al. Pharmacokinetics, pharmacodynamics and pharmacogenomics of efavirenz 400mg once-daily during pregnancy and postpartum. IAS 2017. 23\u201326 July 2017. Paris. Poster abstract TUPDB0203LB.
    \nhttp:\/\/programme.ias2017.org\/Abstract\/Abstract\/5612<\/a><\/li>\n
  2. Schalkwijk S et al. Pharmacokinetics of efavirenz 600 mg QD during pregnancy and postpartum. CROI 2016. 22\u201325 February. Boston. Poster abstract 433.
    \n    http:\/\/www.croiconference.org\/sites\/default\/files\/posters-2016\/433.pdf<\/a>\u00a0 (PDF)<\/li>\n
  3. Puls R et al. Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial. Lancet.\u00a02014 Apr 26;383(9927):1474-82.
    \n    https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24522178<\/a><\/li>\n<\/ol>\n\n","protected":false},"excerpt":{"rendered":"

    Polly Clayden, HIV i-Base Results from a pharmacokinetic (PK) study of 400 mg efavirenz (EFV400) during\u00a0pregnancy, showed lower drug concentrations in the third trimester, compared with post-partum, but these were within adequate ranges described elsewhere. The findings were presented as …<\/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],"tags":[243],"class_list":["post-32228","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pmtct-and-maternal-health","tag-ias-9-paris-2017"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/32228","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=32228"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/32228\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=32228"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=32228"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=32228"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}