CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

proportions of pregnant women with HIV diagnosed prior to pregnancy (80%) (Nesheim, et al, PIDJ, 2019) and on antiretroviral treatment (ART) (58%-74%) (CDC) to estimate annual pregnancies to women on ART at conception. We then utilized data from the North American AIDS Cohort Collaboration on Research and Design from 2007-2016, the most current years available, (Jennifer Lee, personal communication, February 4, 2019) and factored the proportion of women aged 15-45 years with ≥ 1 month exposure to each INSTI to estimate periconceptional INSTI exposures by year. Results: In 2007-2016, women with diagnosed HIV in the United States had an estimated 63,085 pregnancies and 41,005 live births. Among 29,272-37,346 pregnancies conceived by women on ART, an estimated 6,727-8,583 (23%) had periconceptional INSTI exposure, of which 3,694-4,713 (55%) were exposed to raltegravir (RAL), 1,610-2,055 (24%) to DTG, 1,413-1,801 (21%) to elvitegravir (ELV) and none to bictegravir. Periconceptional INSTI use among women on ART increased steadily with 1% exposed in 2007 and 61% in 2016. In 2016, among 1,535-1,959 periconceptional INSTI exposures, 15%were exposed to RAL, 52% to DTG and 33% to ELV. An additional 5,314 pregnancies among women with HIV occurred in 2017; assuming same proportion on INSTIs as in 2016, there would have been an additional 1,492-1903 periconceptional INSTI exposures (746-801 DTG exposures). Conclusion: INSTI use by U.S. women on ART at pregnancy conception has increased. This is the first U.S. national estimate, and ascertainment of exposures will be an important component of monitoring safety of new pharmacologic agents used in pregnancy.

singleton pregnancies, 16 were terminated (1 for birth defects at 29WG for neuronal migration disorder and severe microcephaly, with periconception DTG exposure) and 22 ended in spontaneous abortion; of 10 twin pregnancies, 1 was terminated and in 1, a fetus miscarried. There were 417 live-born infants (229 male, 185 female, 3 missing), born at median 39WG (IQR 38, 40). Five infants were stillborn, all exposed to periconception DTG, none with birth defects. The Table shows birth outcomes for the 400 live-born singleton infants (no twins had birth defects); 266 (67%) had periconception DTG exposure. One neonate died at 2 days (born at 23 GW) with periconception DTG exposure. Among the 417 live-born infants there were 17 with reported birth defects (4.1%, 95% CI 2.4, 6.5); 1 infant had 2 defects. The 18 defects were in the following systems: genitourinary (7), heart (3), limb addition (polydactyly, 3), gastrointestinal (2), other (3); no CNS defects were reported. There were no vertical transmissions (106 infants still indeterminate) Conclusion: The birth defect rate and pattern add further support to current evidence on safety of periconception DTG use. This study is ongoing, in order to provide robust pharmacovigilance data in Europe.

Poster Abstracts

792 CHANGES IN DTG USE FOLLOWING THE NTD SAFETY SIGNAL IN BOTSWANA

Rebecca Zash 1 , Chelsea Morroni 2 , Gloria K. Mayondi 3 , Modiegi D. Diseko 3 , Judith Mabuta 3 , Mompati O. Mmalane 3 , Joseph Makhema 3 , Mimi Raesima 4 , Tendani Gaolathe 3 , Tumalano Sekoto 3 , Shahin Lockman 5 , Roger L. Shapiro 6 1 Beth Israel Deaconess Medical Center, Boston, MA, USA, 2 Liverpool School of Tropical Medicine, Liverpool, UK, 3 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 4 Botswana Ministry of Health, Gaborone, Botswana, 5 Brigham and Women's Hospital, Boston, MA, USA, 6 Harvard T.H. Chan School of Public Health, Boston, MA, USA Background: In May 2018 a preliminary safety signal for neural tube defects among women on dolutegravir (DTG) at conception led to in-country guidance for individualized counseling for pregnant women who had already conceived on DTG and women on DTG or starting antiretroviral treatment (ART) who desired pregnancy; DTG-based ART otherwise remained the recommended regimen for new ART starts. We evaluated patterns of DTG use before and after this guidance. Methods: This is a secondary analysis of data abstracted from Aug 2016-Sept 2019 in the Tsepamo birth outcomes surveillance study. HIV diagnosis date, ART regimens taken before or during pregnancy and dates of ART initiation and discontinuation were collected from all women living with HIV who delivered at study sites. Botswana national HIV treatment guidelines recommended DTG- based ART fromMay 2016 onward, with updated guidance related to pregnancy intention issued in May 2018. Results: Among 20,254 women living with HIV who delivered from Aug 15, 2016-Aug31, 2019, 13,205 (65.2%) were on ART prior to conception, 5,718 (28.2%) started ART during pregnancy, 904 (4.5%) received no ART and 427 (2.1%) had unknown timing of ART start. The proportion of deliveries with DTG conception exposure increased steadily during the study period to a maximum of 30% in 10/2018 (Figure 1a). Among women who likely conceived in the 5 months after the May 2018 guidance, 27% of conceptions were on DTG-based ART, which was unchanged from 28% in the 5 months prior to the guidance. Before May 2018, 97% of women initiating ART in pregnancy started DTG-based ART (1.7%<6 weeks gestational age)(Figure 1b). After May 2018, only 43% of starts in pregnancy were DTG-based ART (1.6%<6 weeks gestational age), and 56% started EFV-based ART. Among 441 who changed ARVs during pregnancy, 177 (40%) switched from DTG-based ART to EFV-based ART (99% after May 2018). Only 71 (0.4%) women completely discontinued ART during pregnancy, including 35 women on DTG and 24 on EFV. Conclusion: Program guidance based on individual counselling regarding pregnancy intention had no apparent impact on the number of women who conceived on DTG-based ART in 2018-2019 in Botswana. However, pregnant women frequently initiated non-DTG-based ART, or switched off DTG-based ART, despite being beyond the NTD risk period. Evaluation of clinician and patient perceptions of the NTD risk, and improvement in understanding

791 OUTCOMES FOLLOWING PRENATAL EXPOSURE TO DOLUTEGRAVIR: THE DOLOMITE-EPPICC STUDY Claire Thorne 1 , Virginia Rasi 1 , Karoline Aebi-Popp 2 , Luminita Ene 3 , Marco Floridia 4 , Natalia Mendoza Palomar 5 , Luis M. Prieto 6 , Leigh Ragone 7 , Rebecca Sconza 1 , Carlo Giaquinto 8 , Vani Vannappagari 7 , for the Dolomite-EPPICC Study Group 1 University College London, London, UK, 2 University Hospital of Bern, Bern, Switzerland, 3 Victor Babes Private Medical Clinic, Bucharest, Romania, 4 Istituto Superiore di Sanità, Rome, Italy, 5 Vall d'Hebron Research Institute, Barcelona, Spain, 6 Hospital Universitario 12 de Octubre, Madrid, Spain, 7 ViiV Healthcare, Research Triangle Park, NC, USA, 8 University of Padova, Padova, Italy Background: Dolutegravir (DTG) was approved for treating HIV in adults and adolescents in 2013. In 2018, the Tsepamo Study reported a significantly increased neural tube defect (NTD) risk in women conceiving on DTG (0.94%), leading to a safety alert. In July 2019, additional data showed NTD prevalence with periconception DTG to be lower than in the initial analysis, but still greater than seen for other antiretroviral exposures (0.3% vs 0.1%). We aimed to assess birth outcomes following prenatal DTG use using real-world data Methods: Dolomite-EPPICC is a multi-cohort European observational study of DTG use in pregnant women living with HIV and their infants. Analysis of prospectively collected individual patient data on all pregnancies with any prenatal DTG exposure and with birth outcomes reported by Feb 2019 was conducted. Periconception exposure was defined as being within the first 6 weeks of gestation (WG). Results: A total of 453 pregnancies in 428 women from 6 cohorts were included. Women were mainly of black African (229, 54%) and white (129, 30%) ethnicity. Most (326/428, 76%) women had heterosexual HIV acquisition, 42 women were vertically infected and 11 had injecting drug use history. Of 443

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