{"id":40691,"date":"2021-06-01T07:40:35","date_gmt":"2021-06-01T07:40:35","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=40691"},"modified":"2021-06-01T08:44:34","modified_gmt":"2021-06-01T08:44:34","slug":"dolutegravir-based-regimens-safe-and-effective-in-pregnancy-and-postpartum","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/40691","title":{"rendered":"Dolutegravir-based regimens safe and effective in pregnancy and postpartum"},"content":{"rendered":"<div><\/div>\n<div>\n<p class=\"HTBsubhead3authorcredit\"><strong><span lang=\"EN-US\"><img loading=\"lazy\" decoding=\"async\" class=\"alignright size-medium wp-image-40209\" src=\"https:\/\/i-base.info\/htb\/wp-content\/uploads\/2021\/03\/CROI-2021-logo-213x300.png\" alt=\"\" width=\"213\" height=\"300\" srcset=\"https:\/\/i-base.info\/htb\/wp-content\/uploads\/2021\/03\/CROI-2021-logo-213x300.png 213w, https:\/\/i-base.info\/htb\/wp-content\/uploads\/2021\/03\/CROI-2021-logo.png 371w\" sizes=\"auto, (max-width: 213px) 100vw, 213px\" \/>Polly Clayden, HIV i-Base<\/span><\/strong><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><b><span lang=\"EN-US\">Two presentations at CROI 2021, showed post-partum data from key studies of dolutegravir in pregnancy.<\/span><\/b><\/p>\n<\/div>\n<div>\n<ul>\n<li class=\"HTBBODYindent\"><span lang=\"EN-US\">VESTED (IMPAACT 2010) compared safety and efficacy of dolutegravir (DTG) + emtricitabine (FTC)\/tenofovir alafenamide fumarate (TAF) vs DTG + FTC\/tenofovir disoproxil fumarate (TDF) vs efavirenz (EFV)\/FTC\/TDF in women starting ART in pregnancy. Results shown were from enrollment through week 50 postpartum (PP). [1]<\/span><\/li>\n<li class=\"HTBBODYindent\">DolPHIN-2 compared safety and efficacy of\u00a0 DTG- vs EFV-based regimens among women starting treatment in the third trimester to in South Africa and Uganda. Final results with follow-up of mothers and infants to 72 weeks PP were shown. [2]<\/li>\n<\/ul>\n<\/div>\n<div><span lang=\"EN-US\">Both studies have previously reported results through delivery [3, 4].<\/span><\/div>\n<p><span>VESTED<\/span><\/p>\n<p><span lang=\"EN-US\">ART-naive pregnant women with HIV in 9 countries (<\/span>Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, US and Zimbabwe \u2013 the majority from Africa) <span lang=\"EN-US\">were randomised 1:1:1 to start open-label DTG + FTC\/TAF vs DTG + FTC\/TDF vs EFV\/FTC\/TDF at 14\u201328 weeks\u2019 gestation.<\/span><\/p>\n<p>Safety outcomes included pairwise comparisons of grade 3 and higher maternal and infant adverse events, infant mortality and infant HIV infection. Efficacy analyses included comparison of maternal viral load &lt;200 copies\/mL at week 50 PP between the combined DTG arms and the EFV arm.<\/p>\n<p>Six hundred and forty three women were randomised to DTG + FTC\/TAF; DTG + FTC\/TDF and EFV\/FTC\/TDF. At baseline median age was 26.6 years, gestational age 21.9 weeks, viral load 903 copies\/mL and CD4 count 466 cells\/mm3. Median baseline BMI was 24.7 \u2013 pre-pregnancy BMI was not available.<\/p>\n<p>There were no apparent differences between arms at week 50 PP in the estimated probability of maternal or infant grade 3 and higher adverse events.<\/p>\n<p>Six hundred and seven (94.4%) women and 566 (91.7%) of 617 liveborn infants completed the study. Three quarters of the infants 479\/617 (77.6%) were breastfed for a median of 49.9 weeks.<\/p>\n<p><span lang=\"EN-US\">There were 20 infant deaths, of which 15 were within 28 days of delivery. The estimated probability of infant death was higher in the EFV arm (6.9%) compared to DTG + FTC\/ TAF (1.0%, p&lt;0.001) and DTG + FTC\/TDF (2.0%, p=0.008) arms. In post-hoc analysis, combining still births and infant deaths, this was highest in the EFV arm (8.5%) compared to DTG + FTC\/ TAF (4.6%) and DTG + FTC\/TDF (7.0%).<\/span><\/p>\n<p>Major congenital anomalies occurred in 4 infants: 2 in DTG + FTC\/TAF arm (atrial septal defect and talipes equinovarus in the right foot) and 2 in EFV\/FTC\/TDF arm (duodenal\u00a0 atresia\/ileal stenosis and subgaleal cyst).<\/p>\n<p>Either stillbirth (previously reported) or infant death (combined) occurred as follows: 10 in DTG + FTC\/TAF, 15 in DTG + FTC\/TDF, and 18 in EFV\/FTC\/TDF arms. Four infants were diagnosed with HIV: 2 in DTG + FTC\/TAF, 1 in DTG + FTC\/TDF, and 1 in EFV arm.<\/p>\n<p>Week 50 PP maternal viral load results were available for 573 (89.1%). Another 30 women had results within an extended window (due to COVID-19).<\/p>\n<p>Proportions of women with viral load &lt;200 copies\/mL were similar in the combined DTG arms (96.3%) and EFV arm (96.4%).<\/p>\n<p>The average weight loss from enrolment through PP was: -0.027 kg\/week in DTG + FTC\/TAF, -0.050 kg\/week in DTG + FTC\/TDF, and -0.084 kg\/week in EFV\/FTC\/TDF arms (p&lt;0.001, DTG + FTC\/TAF vs EFV\/FTC\/TDF). There were no statistical differences in obesity rates between arms at week 50 PP \u2013 although this was highest in the DTG + FTC\/TAF (22.6%) and lowest in the EFV\/FTC\/TDF (15%) arms .<\/p>\n<h2>DOLPHIN-2<\/h2>\n<p>In this study, 268 ART-naive pregnant women at 28 weeks\u2019 gestation or more (safety cohort) were enrolled and randomised to receive EFV- (n=133) or DTG-based ART (n=135). Of those women, 250 (125 EFV and 125 DTG intention-to-treat cohort) were evaluable for efficacy.<\/p>\n<p>At baseline women had a median age of 28 years, viral load 4.5 log10 copies\/mL and CD4 449 cells\/mm3.<\/p>\n<p>Safety outcomes included maternal and\/or infant drug related serious adverse events (SAE). Primary efficacy included maternal viral load &lt;50 copies\/mL.<\/p>\n<p>At week 72 PP, 21.3% of women experienced one or more SAE: DTG 24.4% vs EFV 18.0%. But only 3% were judged to be drug-related. DTG was well tolerated with a lower frequency of drug-related SAE: DTG 2.2% vs EFV 3.8%.<\/p>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">Among the infants, 56.2% experienced one or more SAE, with 24.8% grade 3 or higher. There were 11 infant deaths: DTG 8 vs EFV 3. None of the SAE were judged to be drug-related. The high frequency of SAE was driven primarily by umbilical hernia and birth marks. <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">There were 4 infant HIV infections: 3 in utero in the DTG arm and 1 transmission at week 72 PP in the EFV arm. The late transmission was despite optimal maternal suppression (viral load &lt;50 copies\/mL) at delivery and serial negative tests in the infant. \u00a0<\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">At week 72 PP, 116\/125 mothers receiving DTG achieved viral load &lt;50 copies\/mL with a median time of 4.14 (IQR 4.00 to 5.14) weeks. This compared to the EFV arm in which 114\/125 women achieved suppression at a median of 12.14 (IQR 10.71 to 13.29) weeks: adjusted HR 1.93 (95% CI 1.47 to 2.53), p&lt;0.0001.<\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">For time to viral suppression to &lt;1000 copies\/mL, these values were DTG 1 week (IQR 1 to 2.86) vs EFV 3.71 weeks (IQR 3 to 4): adjusted HR 1.83 (95% CI 1.83 to 2.44), p&lt;0.0001.<\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">There were very few protocol defined failures (failure to achieve &lt;50 copies\/mL by week 24 PP or suppression with subsequent rebound \u2013 2 consecutive results with viral load &gt;1000 copies\/mL). There was a small difference by arm: DTG 2.4% (n=3) vs EFV 6.4% (n=8).\u00a0\u00a0 <\/span><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">The mean change in maternal weight from delivery to 72 weeks PP was -1.2 kg, with nonsignificant differences by arm in weight loss: DTG -0.7 kg vs EFV -1.6 kg. <\/span><\/p>\n<\/div>\n<div>\n<h3 class=\"HTBcommenttitle\"><span lang=\"EN-US\">comment<\/span><\/h3>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><strong><span lang=\"EN-US\">These data are reassuring and support WHO and most national recommendations to use DTG-based ART first-line including for pregnant and lactating women.<\/span><\/strong><\/p>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><strong><span lang=\"EN-US\">The HIV transmission to one infant in the DolPHIN-2 EFV arm, detected at week 72, shows the potential for transmission during breastfeeding despite undetectable viral load. The investigators described the infant feeding as exclusive breastfeeding to 6 months and stopped at 12 months. Maternal adherence included a \u201cslight blip at 24 weeks\u201d.<\/span><\/strong><\/p>\n<p><b>It is not clear how much additional evidence is needed before the UK BHIVA pregnancy guidelines change from the recommendation to still use efavirenz\/boosted PI-based combinations?<span class=\"Apple-converted-space\">\u00a0<\/span><\/b><\/p>\n<\/div>\n<div>\n<p class=\"HTBreferences\"><span lang=\"EN-US\">References<\/span><\/p>\n<\/div>\n<div>\n<ol>\n<li class=\"HTBreferences\"><span lang=\"EN-US\">Chinula L et al. Safety\/efficacy of DTG vs EFV, TDF vs TAF in pregnancy\/ postpartum: IMPAACT 2010 trial.<br \/>\nCROI 2021 (virtual). 6\u201310 March 2021. Oral abstract 177.<br \/>\n<\/span><a href=\"https:\/\/www.croiconference.org\/abstract\/safety-efficacy-of-dtg-vs-efv-tdf-vs-taf-in-pregnancy-postpartum-impaact-2010-trial\/\">https:\/\/www.croiconference.org\/abstract\/safety-efficacy-of-dtg-vs-efv-tdf-vs-taf-in-pregnancy-postpartum-impaact-2010-trial\/<\/a> (abstract)<br \/>\n<a href=\"http:\/\/www.croiwebcasts.org\/p\/2021croi\/croi\/177\">http:\/\/www.croiwebcasts.org\/p\/2021croi\/croi\/177<\/a> (webcast)<\/li>\n<li class=\"HTBreferences\"><span lang=\"EN-US\">Malaba TR et al. DoLPHIN2 final results dolutegravir vs efavirenz in late pregnancy to 72w postpartum. <\/span>CROI 2021 (virtual). 6\u201310 March 2021. Oral abstract 175.<br \/>\n<a href=\"https:\/\/www.croiconference.org\/abstract\/dolphin2-final-results-dolutegravir-vs-efavirenz-in-late-pregnancy-to-72w-postpartum\/\">https:\/\/www.croiconference.org\/abstract\/dolphin2-final-results-dolutegravir-vs-efavirenz-in-late-pregnancy-to-72w-postpartum\/<\/a> (abstract)<br \/>\n<a href=\"http:\/\/www.croiwebcasts.org\/p\/2021croi\/croi\/175\">http:\/\/www.croiwebcasts.org\/p\/2021croi\/croi\/175<\/a> (webcast)<\/li>\n<li class=\"HTBreferences\">Clayden P. Dolutegravir-based ART is safe and effective for pregnant women: first results from the VESTED trial. HTB. 17 April 2020.<br \/>\n<a href=\"https:\/\/i-base.info\/htb\/37534\">https:\/\/i-base.info\/htb\/37534<\/a><\/li>\n<li class=\"HTBreferences\">Clayden P. Dolutegravir suppresses viral load faster than efavirenz in late pregnancy: results from DolPHIN-2. HTB. 12 March 2019.<br \/>\n<a href=\"https:\/\/i-base.info\/htb\/35794\">https:\/\/i-base.info\/htb\/35794<\/a><\/li>\n<\/ol>\n<\/div>\n<div>\n<p class=\"HTBBODYtext\"><span lang=\"EN-US\">\u00a0<em>This report was first posted on 21 May 2021.<\/em><\/span><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Polly Clayden, HIV i-Base Two presentations at CROI 2021, showed post-partum data from key studies of dolutegravir in pregnancy. VESTED (IMPAACT 2010) compared safety and efficacy of dolutegravir (DTG) + emtricitabine (FTC)\/tenofovir alafenamide fumarate (TAF) vs DTG + FTC\/tenofovir disoproxil &hellip;<\/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":[307],"class_list":["post-40691","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pmtct-and-maternal-health","tag-croi-2021-virtual"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/40691","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=40691"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/40691\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=40691"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=40691"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=40691"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}