{"id":35918,"date":"2019-03-28T09:43:09","date_gmt":"2019-03-28T09:43:09","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=35918"},"modified":"2019-03-29T13:37:18","modified_gmt":"2019-03-29T13:37:18","slug":"double-dose-levonorgestrel-implant-does-not-overcome-interaction-with-efavirenz","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/35918","title":{"rendered":"Double-dose levonorgestrel implant does not overcome interaction with efavirenz"},"content":{"rendered":"

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

Using two levonorgestrel (LNG) implants does not fully overcome the drug-drug interaction with efavirenz (EFV) \u2013 according to findings from a <\/span><\/b>pharmacokinetic (PK) evaluation of double-dose LNG in Ugandan women receiving EFV-based ART. [1]<\/span><\/b>\u00a0 <\/span><\/b><\/b><\/p>\n

Kim Scarsi presented these data at CROI 2019 on behalf of investigators from University of Nebraska Medical Center; Infectious Disease Institute, Kampala; Northwestern University, Chicago; and University of Liverpool.<\/span><\/p>\n

LNG is primarily metabolised in the liver by cytochrome P450 (CYP) 3A4. EFV decreases progestin exposure through induction of cytochrome P450.<\/span><\/p>\n

LNG subdermal implants can be left in place for up to 5 years and are a highly effective form of contraception with less than 1% risk of unintended pregnancy.\u00a0\u00a0<\/span><\/p>\n

Professor Scarsi\u2019s group previously found 45\u201357% lower LNG exposure in women using the implant at standard dose (150mg) with EFV-based ART compared to ART-naive women. [2, 3] <\/span><\/p>\n

In that earlier study, 3 of 20 women (15%) had an unintended pregnancy within 48 weeks of combined LNG-EFV use. LNG concentrations were \u2264303 pg\/mL in the 3 women at the visit before pregnancy; 18 (90%) women had any LNG concentration \u2264303 pg\/mL during the study.<\/span><\/p>\n

The aim of the study presented was to see if the LNG-EFV interaction could be overcome with double-dose LNG (300 mg) implants over 48 weeks in women receiving EFV-based ART, compared with historical controls.<\/span><\/p>\n

It was an open label, sparse-sampling PK study. Women receiving EFV 600 mg based ART, with undetectable viral load, had LNG implants placed sub-dermally in each upper arm (DoubLNG group; n=28). All participants were also given a copper IUD as an additional form of contraception. <\/span><\/p>\n

Historical controls were ART-naive Ugandan women (n=17) who received a standard-dose LNG implant. <\/span><\/p>\n

Sampling was performed pre-implant and at weeks 1, 4, 12, 24, 36, and 48. There were optional study visits for 4 weeks after week 48 to assess endogenous progesterone as an indicator of ovarian activity (threshold 3 or 4 ng\/mL).<\/span><\/p>\n

All women were black African. The DoubLNG group was a median age of 33 years and median weight of 58 kg; the control group was 29 years and 69 kg. <\/span><\/p>\n

At week 48, LNG concentrations were 373 pg\/mL (319 to 540) in the DoubLNG group vs 651 pg\/mL (469 to 879) in the control group: GMR 0.66 (90% CI 0.61 to 0.72), p=0.003. This reduction in exposure was similar weeks 1 through 48.<\/span><\/p>\n

Despite the double-dose of LNG implants, concentrations remained 33\u201344% lower in women receiving EFV-based ART plus LNG vs ART-naive women on standard dose LNG.\u00a0<\/span><\/p>\n

More women in the DoubLNG group vs the control group had any LNG value \u2264303 pg\/mL: 13 (46%) vs 3 (18%), respectively, p=0.06. About 90% were below this threshold in the earlier study.\u00a0 <\/span><\/p>\n

Approximately 20\u201325% of participants in the DoubLNG group (n=24) had endogenous serum progesterone levels reflecting ovulation vs 10\u201315% expected to have ovulation in the first year of LNG use, based on historical data.\u00a0 <\/span><\/p>\n

comment<\/span><\/h3>\n

The reduction in concentrations was smaller with the double-dose compared with the standard dose used in the earlier study: 34 vs 57%. But although it increased exposure a bit, doubling the dose of LNG implants did not fully overcome the interaction with EFV.<\/span><\/strong><\/p>\n

Professor Scarsi described this as a \u201csurprising finding\u201d and explained that the contraceptive effectiveness of this approach remains uncertain. She remarked that these results may have complicated the challenges around providing contraception for women on EFV-based ART.<\/span><\/strong><\/p>\n

References<\/span><\/p>\n

    \n
  1. Scarsi K et al. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. CROI 2019. Seattle. 4\u20137 March 2019. Oral abstract 51.
    \n<\/span>http:\/\/www.croiconference.org\/sessions\/double-dose-levonorgestrel-implant-does-not-fully-overcome-interaction-efavirenz<\/a> (abstract)
    \n    http:\/\/www.croiwebcasts.org\/p\/2019croi\/51<\/a>\u00a0<\/span>(webcast)<\/span><\/li>\n
  2. Clayden P. Unintended pregnancies with levonorgestrel implant due to drug interactions with efavirenz-based ART. HTB. 24 March 2015.
    \n    https:\/\/i-base.info\/htb\/28063<\/a><\/li>\n
  3. Scarsi K et al. Unintended pregnancies observed with combined use of the levonorgestrel contraceptive implant and efavirenz-based antiretroviral therapy: a three-arm pharmacokinetic evaluation over 48 weeks. Clin Infect Dis. Volume 62, Issue 6. 15 March 2016.
    \n    https:\/\/academic.oup.com\/cid\/article\/62\/6\/675\/2462703<\/a><\/li>\n<\/ol>\n

    \u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

    Polly Clayden, HIV i-Base Using two levonorgestrel (LNG) implants does not fully overcome the drug-drug interaction with efavirenz (EFV) \u2013 according to findings from a pharmacokinetic (PK) evaluation of double-dose LNG in Ugandan women receiving EFV-based ART. [1]\u00a0 Kim Scarsi …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,44,34],"tags":[264],"class_list":["post-35918","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-womens-health","category-pk-and-drug-interactions","tag-croi-2019"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35918","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=35918"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35918\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=35918"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=35918"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=35918"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}