{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:58:17Z","timestamp":1792979897630,"version":"4.5.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","funder":[{"DOI":"10.13039\/100017973","name":"International Maternal Pediatric Adolescent AIDS Clinical Trials Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017973","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI068632"],"award-info":[{"award-number":["UM1AI068632"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI068616"],"award-info":[{"award-number":["UM1AI068616"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI106716"],"award-info":[{"award-number":["UM1AI106716"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN275201800001I"],"award-info":[{"award-number":["HHSN275201800001I"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1 AI069465"],"award-info":[{"award-number":["UM1 AI069465"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>TB APPRISE (IMPAACT P1078), a Phase IV randomized, multi-country non-inferiority trial assessing the safety of 28 weeks of isoniazid preventive therapy (IPT) initiated during pregnancy (immediate IPT) versus deferring to week 12 postpartum (deferred IPT) in people with HIV on antiretroviral therapy, showed higher than expected hepatotoxicity. We investigated the potential roles of antiretrovirals, isoniazid, pharmacogenetics and other factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Hepatotoxicity was defined as Grade \u22653 liver enzyme elevations; or Grade \u22652 enzyme elevations with elevated bilirubin or symptomatic hepatitis. We performed Poisson regression of all-cause hepatotoxicity on study arm, antiretroviral regimen, pharmacogenetics of isoniazid and efavirenz metabolism (NAT2, CYP2B6) and other participant characteristics. Adjusted models included study arm and covariates with P &amp;lt; .25 in unadjusted models. Antiretroviral regimen and pharmacogenetics interactions with study arm were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All 945 pregnant participants with follow-up liver function measurements were on antiretrovirals (85% with efavirenz, 13% with nevirapine); 63 (6%) experienced hepatotoxicity events; 29 (6%) in immediate, and 34 (7%) in deferred arm; only 5 events (8%) occurred in pregnancy; 49 (78%) occurred between delivery and 24 weeks postpartum. Higher risk of hepatotoxicity was observed with nevirapine use in the immediate arm, but there was no difference by study arm in participants on efavirenz. Slow efavirenz metabolizers had increased risk of hepatotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>It is critical to monitor for hepatotoxicity in early postpartum, where there is higher risk compared to antepartum. ARV regimen and pharmacogenetics should also be considered in making decisions on when to initiate IPT in pregnant and postpartum populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaf198","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T07:24:30Z","timestamp":1744701870000},"page":"e156-e164","source":"Crossref","is-referenced-by-count":4,"title":["Hepatotoxicity Among People With HIV and Receiving Isoniazid Preventive Therapy in Pregnancy and Postpartum: The Role of Antiretroviral Regimen and Pharmacogenetics"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6866-4335","authenticated-orcid":false,"given":"Grace","family":"Montepiedra","sequence":"first","affiliation":[{"name":"Center for Biostatistics in AIDS Research, Harvard T.H. 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Chan School of Public Health , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Theron","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"McCarthy","sequence":"additional","affiliation":[{"name":"FHI 360 , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bradford","sequence":"additional","affiliation":[{"name":"FHI 360 , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsungai","family":"Chipato","sequence":"additional","affiliation":[{"name":"University of Zimbabwe College of Health Sciences Clinical Trials Research Centre , Harare ,","place":["Zimbabwe"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tichaona","family":"Vhembo","sequence":"additional","affiliation":[{"name":"University of Zimbabwe College of Health Sciences Clinical Trials Research Centre , Harare ,","place":["Zimbabwe"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda","family":"Stranix-Chibanda","sequence":"additional","affiliation":[{"name":"University of Zimbabwe College of Health Sciences Clinical Trials Research Centre , Harare ,","place":["Zimbabwe"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deo","family":"Wabwire","sequence":"additional","affiliation":[{"name":"Makerere University-Johns Hopkins University Research Collaboration , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2388-9637","authenticated-orcid":false,"given":"Gaerolwe","family":"Masheto","sequence":"additional","affiliation":[{"name":"Botswana Harvard AIDS Institute Health Partnership , Gaborone ,","place":["Botswana"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Jean-Philippe","sequence":"additional","affiliation":[{"name":"Division of AIDS, National Institute of Allergy and Infectious Diseases , Bethesda, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R","family":"Sterling","sequence":"additional","affiliation":[{"name":"Vanderbilt Tuberculosis Center, Vanderbilt University Medical Center , Nashville, Tennessee ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6920-0623","authenticated-orcid":false,"given":"Adriana","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]},{"name":"Department Medicine and Pathology, University of Colorado Anschutz Medical Campus , Aurora, Colorado ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7036-2718","authenticated-orcid":false,"given":"Amita","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"2026071623564866400_ciaf198-B1","doi-asserted-by":"crossref","DOI":"10.54394\/CJQU6666","volume-title":"Global tuberculosis report 2024","author":"World Health Organization","year":"2024"},{"key":"2026071623564866400_ciaf198-B2","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1093\/cid\/cis732","article-title":"Tuberculosis in pregnant and postpartum women: epidemiology, management, and research gaps","volume":"55","author":"Mathad","year":"2012","journal-title":"Clin Infect Dis"},{"key":"2026071623564866400_ciaf198-B3","volume-title":"WHO Consolidated guidelines on tuberculosis. 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