CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

747 InSTI EXPOSURE AND NEURAL TUBE DEFECTS: DATA FROM ANTIRETROVIRAL PREGNANCY REGISTRY

Jessica D. Albano 1 , Vani Vannappagari 2 , Angela Scheuerle 3 , Heather Watts 4 , Claire Thorne 5 , Leslie Ng 6 , Veronica V. Urdaneta 7 , Lynne M. Mofenson 8 1 Syneos Health, Wilmington, NC, USA, 2 ViiV Healthcare, Research Triangle Park, NC, USA, 3 University of Texas Southwestern, Dallas, TX, USA, 4 US Department of State, Washington, DC, USA, 5 UCL Great Ormond Street Institute of Child Health, London, UK, 6 Gilead Sciences, Inc, Foster City, CA, USA, 7 Merck & Co, Inc, Kenilworth, NJ, USA, 8 Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA Background: Dolutegravir (DTG) is an integrase strand transfer inhibitor (InSTI) with once-daily dosing, good viral efficacy, high barrier to resistance, and good tolerability. Preliminary data from the NIH-supported Botswana birth defects surveillance project (Tsepamo study) reported a potential increased risk of neural tube defects (NTD) in infants born to HIV-positive women receiving DTG- based antiretroviral therapy (ART) prior to conception, compared to non-DTG ART or to uninfected women (0.9%, 0.1% , and 0.09%, respectively). Using data from the Antiretroviral Pregnancy Registry (APR), a voluntary, international, prospective exposure-registration cohort study with independent Advisory Committee oversight, we describe central nervous system (CNS) defects and NTD in infants born to women receiving InSTIs. Methods: Data on prospectively enrolled pregnancies through 31Jan2018 with birth outcome are summarized. Birth defects are reviewed by a dysmorphologist, coded according to modified Metropolitan Atlanta Congenital Defects Program criteria, classified by organ system and assigned timing of exposure to each InSTI (DTG, elvitegravir [EVG], raltegravir [RAL]). Birth defects within the CNS organ system include both NTDs and encephalocele, which is reported separately from NTD. Results: A total of 19,688 pregnancies resulted in 20,026 fetal outcomes including 18,685 live births. APR reports come from North America (75%), Europe (8%), Africa (7%), South America (6%) and Asia (4%). There were 1,021 live births with an InSTI exposure at any time during pregnancy, of which 507 had ongoing exposure at conception, including 121 DTG, 155 EVG, and 231 RAL live birth outcomes. There were no NTD or other CNS birth defects among prospective cases for any InSTI drug (Table). Conclusion: No occurrences of CNS defects or NTDs were observed among 1,021 prospective live birth outcomes with InSTI exposure at any time. This frequency is consistent with the observed low prevalence of NTD in developed countries (~0.1%), as most APR reports (83%) come from North America and Europe where food is supplemented with folate, which reduces NTD prevalence. However, InSTIs are a newer class of ARVs and the number of pregnancies with InSTI exposure in the APR to date is insufficient to draw definitive conclusions about a potential association between DTG and NTD, or to look at specific geographic regions. Healthcare providers are encouraged to continue to report pregnancies with prospective antiretroviral exposures to the APR.

Poster Abstracts

748 UGANDAN CLINIC EXPERIENCE FOLLOWING POTENTIAL TERATOGENICITY ALERT FOR DOLUTEGRAVIR Arinaitwe S. Arnold , Eva A. Laker Odongpiny, Noela Owarwo, Onzia Annet, Nasasira Benson, Wailagala Abdullah, Ivan Kalule, Anguzu Godwin, Agnes Kiragga, Kay Seden, Barbara Castelnuovo, Isaac Lwanga, Rachel Musomba, Mohammed Lamorde Infectious Disease Institute, Kampala, Uganda Background: In 2017, the Infectious Disease Institute (IDI) introduced dolutegravir (DTG)-based regimens in its Kampala clinic in Uganda. In May 2018, the WHO and international regulators released warnings on a possible increased risk of neural tube defects in infants born to women taking DTG at the time of conception. In response, IDI implemented a process to inform and support women already on DTG to make informed treatment choices. Methods: A clinic response plan was developed in the first week following the alert and clinic staff were trained on safety guidance. All women <55 years on DTG were identified from the clinic database and contacted by phone for earlier appointments. FromMay-June, group counselling sessions (<15 women/ group) were held. Non-menopausal and non-surgically sterilized women were referred for urine pregnancy testing, evaluation of pregnancy intentions in next 12 months and effective family planning was offered (preferably condoms plus implants, IUDs, depo-provera or pills). Pregnancies were confirmed by ultrasound and obstetrician review. Women intending to conceive were offered efavirenz (EFV)-based regimens. Women that chose to remain on DTG without effective family planning signed a declaration of informed choice. We used modified Poisson regression to determine factors associated with switching off DTG. Results: 9% (692/7963) were identified to be on DTG and 95% (658/692) were reviewed by September 2018. 22% (146/658) were menopausal or surgically sterilized. 510 women were of reproductive potential with median age (IQR); 37 (30 - 42) and mean duration (SD) on DTG of 4.26 months (1.63). 5% (23/510) were HCG positive and all initial ultrasound reports revealed no deformities. 21% (108/510) had intentions to conceive and opted to be switched off DTG with 90% (97/108) switched to EFV. 79% (402/510) opted to stay on DTG. However only, 40% (160/402) chose effective contraceptives methods and 60% (242/402) opted for condoms only/no contraceptive method. Factors associated with switching off DTG were younger age (Prevalence Ratio (PR) 0.96 [95% CI: 0.94, 0.99, p=0.002]) and not using effective contraception (PR 0.04 [95% CI: 0.01,0.15, p<0.001]).

CROI 2019 288

Made with FlippingBook - Online Brochure Maker