{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:30:06Z","timestamp":1791387006392,"version":"4.3.3"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CHIP clinic","award":["HHSN275201800001I; 5P01HD103133-02; 5U01HD068063-05; 5U01HD068040474-15S1; UM1 AI068619; ENVHL-202158734-00; X0700056; H12HA24784"],"award-info":[{"award-number":["HHSN275201800001I; 5P01HD103133-02; 5U01HD068063-05; 5U01HD068040474-15S1; UM1 AI068619; ENVHL-202158734-00; X0700056; H12HA24784"]}]},{"name":"NIH\/NCATS Colorado CTSA","award":["UL1 TR002535"],"award-info":[{"award-number":["UL1 TR002535"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antiretroviral therapy (ART) decreases perinatal HIV transmission, but concerns exist regarding maternal and infant safety. We compared the incidence of congenital malformations and other adverse outcomes in pregnancies exposed to integrase inhibitor (INSTI) versus non-INSTI ART.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Single-site review of all pregnancies among women living with HIV between 2008 and 2018.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used binomial family generalized estimating equations to model the relationship of congenital anomalies and pregnancy outcomes with exposure to INSTI or dolutegravir (DTG) versus non-INSTI ART.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 257 pregnancies, 77 women received \u22651 INSTI (54 DTG, 14 elvitegravir, 15 raltegravir), 167 received non-INSTI, and 3 had missing data. Fifty congenital anomalies were identified in 36 infants. Infants with first-trimester DTG or any first-trimester INSTI exposure had higher odds of congenital anomalies than infants with first-trimester non-INSTI exposure (OR = 2.55; 95%CI = 1.07\u20136.10; OR = 2.61; 95%CI = 1.15\u20135.94, respectively). Infants with INSTI exposure after the second trimester had no increased odds of anomalies. Women with INSTI exposure had higher odds of preeclampsia (OR = 4.73; 95%CI = 1.70\u201313.19). Among women who received INSTI, grade \u22653 laboratory abnormalities were noted in 2.6% while receiving the INSTI and 3.9% while not receiving the INSTI, versus 16.2% in women who received non-INSTI. There was no association between INSTI exposure and other pregnancy outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In our cohort, first-trimester INSTI exposure was associated with increased rates of congenital anomalies and use of INSTI during pregnancy was associated with preeclampsia. These findings underscore the need for continued monitoring of the safety of INSTI in pregnancy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0276473","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T13:31:37Z","timestamp":1686576697000},"page":"e0276473","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Congenital malformations and preeclampsia associated with integrase inhibitor use in pregnancy: A single-center analysis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4611-6477","authenticated-orcid":true,"given":"Christiana","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela J.","family":"Fought","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce F.","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1641-9610","authenticated-orcid":true,"given":"Jennifer R.","family":"McKinney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torri D.","family":"Metz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6903-0644","authenticated-orcid":true,"given":"Kirk B.","family":"Fetters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Lazarus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Capraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Barr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Glenny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Buehler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6920-0623","authenticated-orcid":true,"given":"Adriana","family":"Weinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the CHIP Perinatal Medical Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"pone.0276473.ref001","unstructured":"Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. [Available from: https:\/\/clinicalinfo.hiv.gov\/en\/guidelines\/perinatal]."},{"issue":"10","key":"pone.0276473.ref002","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1056\/NEJMc1807653","article-title":"Neural-Tube Defects with Dolutegravir Treatment from the Time of Conception","volume":"379","author":"R Zash","year":"2018","journal-title":"N Engl J Med"},{"key":"pone.0276473.ref003","first-page":"2020","article-title":"Update on Neural Tube Defects with Antiretroviral Exposure in the Tsepamo Study, Botswana.","author":"R Zash","year":"2020","journal-title":"AIDS 2020"},{"key":"pone.0276473.ref004","author":"C Thorne","year":"2020","journal-title":"Outcomes following prenatal exposure to dolutegravir: The DOLOMITE-EPPICC Study Conference on Retroviruses and Opportunistic Infections"},{"issue":"1","key":"pone.0276473.ref005","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1016\/S2352-3018(20)30268-X","article-title":"Dolutegravir and pregnancy outcomes in women on antiretroviral therapy in Brazil: a retrospective national cohort study","volume":"8","author":"GFM Pereira","year":"2021","journal-title":"Lancet HIV"},{"key":"pone.0276473.ref006","article-title":"Maternal Dolutegravir (DTG) Use, and Pregnancy and Birth Outcomes: The Antiretroviral Pregnancy Registry (APR).","author":"V Vannappagari","year":"2021","journal-title":"IDWeek"},{"key":"pone.0276473.ref007","author":"World Health Organization","year":"2019","journal-title":"WHO recommends dolutegravir as preferred HIV treatment option in all populations"},{"issue":"1","key":"pone.0276473.ref008","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1097\/QAI.0000000000002213","article-title":"Postmarketing Surveillance of Pregnancy Outcomes With Dolutegravir Use.","volume":"83","author":"M Crawford","year":"2020","journal-title":"J Acquir Immune Defic Syndr."},{"issue":"6","key":"pone.0276473.ref009","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1097\/QAD.0000000000001755","article-title":"Dolutegravir pharmacokinetics in pregnant and postpartum women living with HIV","volume":"32","author":"N Mulligan","year":"2018","journal-title":"Aids"},{"issue":"9","key":"pone.0276473.ref010","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1097\/QAD.0000000000002550","article-title":"Safety of in-utero antiretroviral exposure: neurologic outcomes in children who are HIV-exposed but uninfected","volume":"34","author":"CS Crowell","year":"2020","journal-title":"AIDS"},{"key":"pone.0276473.ref011","author":"Antiretroviral Pregnancy Registry Steering Committee","year":"2020","journal-title":"Antiretroviral Pregnancy Registry Interim Report for 1 January 1989 through 31 January 2020 Wilmington NC: Registry Coordinating Center"},{"issue":"11","key":"pone.0276473.ref012","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1111\/1471-0528.15838","article-title":"Congenital anomalies following antenatal exposure to dolutegravir: a Canadian surveillance study.","volume":"126","author":"D Money","year":"2019","journal-title":"BJOG."},{"issue":"4","key":"pone.0276473.ref013","doi-asserted-by":"crossref","first-page":"ofz129","DOI":"10.1093\/ofid\/ofz129","article-title":"A Multicenter Analysis of Elvitegravir Use During Pregnancy on HIV Viral Suppression and Perinatal Outcomes.","volume":"6","author":"ML Badell","year":"2019","journal-title":"Open Forum Infect Dis."},{"issue":"3","key":"pone.0276473.ref014","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1097\/QAI.0000000000001924","article-title":"Brief Report: Surveillance of Congenital Anomalies After Exposure to Raltegravir or Elvitegravir During Pregnancy in the United Kingdom and Ireland, 2008\u20132018.","volume":"80","author":"V Rasi","year":"2019","journal-title":"J Acquir Immune Defic Syndr."},{"issue":"2","key":"pone.0276473.ref015","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1097\/QAD.0000000000002719","article-title":"Risk of birth defects and perinatal outcomes in HIV-infected women exposed to integrase strand inhibitors during pregnancy","volume":"35","author":"J Sibiude","year":"2021","journal-title":"Aids"},{"issue":"7","key":"pone.0276473.ref016","doi-asserted-by":"crossref","first-page":"e804","DOI":"10.1016\/S2214-109X(18)30218-3","article-title":"Comparative safety of dolutegravir-based or efavirenz-based antiretroviral treatment started during pregnancy in Botswana: an observational study","volume":"6","author":"R Zash","year":"2018","journal-title":"Lancet Glob Health"},{"issue":"10281","key":"pone.0276473.ref017","first-page":"1276","article-title":"Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010\/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial.","volume":"397","author":"S Lockman","year":"2021","journal-title":"Lancet Infect Dis"},{"issue":"3","key":"pone.0276473.ref018","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1097\/QAI.0000000000002445","article-title":"Repeat Pregnancies Among US Women Living With HIV in the SMARTT Study: Temporal Changes in HIV Disease Status and Predictors of Preterm Birth","volume":"85","author":"BE O\u2019Brien","year":"2020","journal-title":"Journal of acquired immune deficiency syndromes"},{"key":"pone.0276473.ref019","first-page":"2021","article-title":"The Risk of Gestational Hypertension with Use of Dolutegravir at Conception.","volume":"10","author":"R Zash","year":"2021","journal-title":"Conference on Retroviruses and Opportunistic Infections"},{"key":"pone.0276473.ref020","unstructured":"Chadwick EG, Jacobson D, Haddad L, Jao J, Powis KM, Kacanek D, et al., editors. Timing of ART is Associated with Hypertensive Disorders of Pregnancy. Conference on Retroviruses and Opportunistic Infections; March 6\u201310, 2021; (Held virtually due to COVID-19)."},{"issue":"2","key":"pone.0276473.ref021","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)\u2014a metadata-driven methodology and workflow process for providing translational research informatics support.","volume":"42","author":"PA Harris","year":"2009","journal-title":"J Biomed Inform"},{"issue":"2","key":"pone.0276473.ref022","doi-asserted-by":"crossref","first-page":"e214","DOI":"10.1542\/peds.2009-0913","article-title":"New intrauterine growth curves based on United States data","volume":"125","author":"IE Olsen","year":"2010","journal-title":"Pediatrics"},{"key":"pone.0276473.ref023","year":"2017","journal-title":"Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events"},{"key":"pone.0276473.ref024","volume-title":"UpToDate","author":"FC Cunningham","year":"2020"},{"key":"pone.0276473.ref025","doi-asserted-by":"crossref","first-page":"S428","DOI":"10.1093\/cid\/ciu738","article-title":"Assessment of congenital anomalies in infants born to pregnant women enrolled in clinical trials","volume":"597","author":"SA Rasmussen","year":"2014","journal-title":"Clin Infect Dis"},{"key":"pone.0276473.ref026","doi-asserted-by":"crossref","first-page":"894627","DOI":"10.3389\/fped.2022.894627","article-title":"Congenital Co-infections Among HIV-Exposed Infants Born to Mothers on Antiretroviral Treatment in the United States.","volume":"10","author":"C Smith","year":"2022","journal-title":"Front Pediatr."},{"key":"pone.0276473.ref027","unstructured":"Smith M-SR, Cote HC, editors. Toxicity of Integrase Inhibitors in a Human Embryonic Stem-Cell Model. Conference on Retroviruses and Opportunistic Infections; March 8\u201311, 2020; (Held virtually due to COVID-19)."},{"key":"pone.0276473.ref028","article-title":"Some InSTIs Induce Toxicity and Differentiation in Human Embryonic Stem Cells.","author":"M-SR Smith","year":"2022","journal-title":"Conference on Retroviruses and Opportunistic Infections"},{"key":"pone.0276473.ref029","first-page":"1","article-title":"Update on Overall Prevalence of Major Birth Defects\u2014Atlanta, Georgia, 1978\u20132005","volume":"57","author":"L Rynn","year":"2008","journal-title":"Morbidity and Mortality Weekly Report"},{"issue":"16","key":"pone.0276473.ref030","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1097\/QAD.0000000000001610","article-title":"Antiretroviral combination use during pregnancy and the risk of major congenital malformations","volume":"31","author":"A Berard","year":"2017","journal-title":"AIDS"},{"issue":"1","key":"pone.0276473.ref031","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1001\/jamapediatrics.2014.1889","article-title":"Congenital anomalies and in utero antiretroviral exposure in human immunodeficiency virus-exposed uninfected infants","volume":"169","author":"PL Williams","year":"2015","journal-title":"JAMA Pediatr"},{"issue":"2","key":"pone.0276473.ref032","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1097\/INF.0b013e318235c7aa","article-title":"Prevalence of congenital anomalies in infants with in utero exposure to antiretrovirals.","volume":"31","author":"KM Knapp","year":"2012","journal-title":"Pediatr Infect Dis J"},{"issue":"4","key":"pone.0276473.ref033","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1097\/QAI.0000000000002035","article-title":"Eppicc. Pregnancy and Neonatal Outcomes Following Prenatal Exposure to Dolutegravir","volume":"81","author":"V Vannappagari","year":"2019","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"5","key":"pone.0276473.ref034","doi-asserted-by":"crossref","first-page":"e332","DOI":"10.1016\/S2352-3018(20)30050-3","article-title":"Dolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial.","volume":"7","author":"K Kintu","year":"2020","journal-title":"Lancet HIV"},{"issue":"3","key":"pone.0276473.ref035","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/QAI.0000000000002447","article-title":"Metabolic Changes Associated With the Use of Integrase Strand Transfer Inhibitors Among Virally Controlled Women.","volume":"85","author":"NA Summers","year":"2020","journal-title":"J Acquir Immune Defic Syndr."},{"issue":"8","key":"pone.0276473.ref036","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/hiv.13120","article-title":"Gestational diabetes in women living with HIV in Botswana: lower rates with dolutegravir- than with efavirenz-based antiretroviral therapy","volume":"22","author":"KN Mmasa","year":"2021","journal-title":"HIV Med"},{"key":"pone.0276473.ref037","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12978-016-0149-5","article-title":"Is protease inhibitors based antiretroviral therapy during pregnancy associated with an increased risk of preterm birth? Systematic review and a meta-analysis","volume":"13","author":"YM Mesfin","year":"2016","journal-title":"Reprod Health"},{"issue":"5","key":"pone.0276473.ref038","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1097\/QAI.0000000000002072","article-title":"Risk Factors for Adverse Birth Outcomes in the PROMISE 1077BF\/1077FF Trial.","volume":"81","author":"D Sebikari","year":"2019","journal-title":"J Acquir Immune Defic Syndr."},{"key":"pone.0276473.ref039","doi-asserted-by":"crossref","first-page":"867674","DOI":"10.1155\/2011\/867674","article-title":"Safety and tolerability of antiretrovirals during pregnancy.","volume":"2011","author":"A Weinberg","year":"2011","journal-title":"Infectious diseases in obstetrics and gynecology."},{"issue":"5","key":"pone.0276473.ref040","doi-asserted-by":"crossref","first-page":"e322","DOI":"10.1016\/S2352-3018(20)30038-2","article-title":"Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial.","volume":"7","author":"EC Joao","year":"2020","journal-title":"Lancet HIV"},{"issue":"2","key":"pone.0276473.ref041","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1093\/cid\/civ260","article-title":"In utero exposure to zidovudine and heart anomalies in the ANRS French perinatal cohort and the nested PRIMEVA randomized trial.","volume":"61","author":"J Sibiude","year":"2015","journal-title":"Clinical infectious diseases: an official publication of the Infectious Diseases Society of America."},{"issue":"9","key":"pone.0276473.ref042","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1097\/QAD.0000000000001066","article-title":"Zidovudine treatment in HIV-infected pregnant women is associated with fetal cardiac remodelling","volume":"30","author":"L Garcia-Otero","year":"2016","journal-title":"AIDS"},{"issue":"4","key":"pone.0276473.ref043","doi-asserted-by":"crossref","first-page":"e1001635","DOI":"10.1371\/journal.pmed.1001635","article-title":"Association between prenatal exposure to antiretroviral therapy and birth defects: an analysis of the French perinatal cohort study (ANRS CO1\/CO11).","volume":"11","author":"J Sibiude","year":"2014","journal-title":"PLoS medicine."},{"key":"pone.0276473.ref044","doi-asserted-by":"crossref","first-page":"i1753","DOI":"10.1136\/bmj.i1753","article-title":"High Risk of Pre-eclampsia Identification G. Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies","volume":"353","author":"E Bartsch","year":"2016","journal-title":"Bmj"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0276473","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T13:32:20Z","timestamp":1686576740000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0276473"}},"subtitle":[],"editor":[{"given":"Carlo","family":"Torti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,6,12]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0276473","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.10.10.22280923","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,12]]}}}