{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:40:39Z","timestamp":1776069639186,"version":"3.50.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We analysed the association between host genetic risk scores (GRSs) predicting efavirenz (EFV) plasma levels and exposure and suicidal behaviours in participants in one of several global antiretroviral therapy (ART) clinical trials linked to the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a matched case\u2013control study (two controls per case) on suicide or grade-4 suicidal ideation\/attempts or depression. Cases and controls were matched by EFV initiation strategy, study, and follow-up time. CYP2B6-based GRS classified participants as extensive, intermediate, or slow metabolisers. EFV and its metabolites (8-hydroxy-EFV and 7-hydroxy-EFV) were measured in plasma. Conditional logistic regression was used to analyse the associations between GRS categories, EFV levels, and suicidal behaviour.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 74 cases and 146 controls, 128 (58.2%) started EFV-containing first-line treatment. Of the treatment-experienced participants, 35% were on EFV at entry. Pre-existing psychiatric conditions and recreational drug-use were more common in cases (16.2%, 25.7%) than in controls (0.7%, 9.6%). On comparing cases to controls, more cases were extensive metabolisers (52% vs. 45%), but there were fewer slow metabolisers (8% vs. 13%). The unadjusted odds ratio (OR) for suicidal behaviour per one more minor allele was 0.76 (95% CI: 0.49\u20131.18). The OR for being a case vs. a control was 0.57 (95% CI: 0.38\u20130.86) per doubling of the EFV plasma level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CYP2B6-based GRS for cytochrome P450 enzymatic activity appeared not to be associated with suicidal behaviour in individuals living with HIV treated with EFV-containing ART combinations. CYP2B6-based GRS effectively predicted EFV exposure, but suicidal behaviour appeared more likely in extensive (normal) metabolisers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1734919","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T07:40:54Z","timestamp":1776066054000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CYP2B6 polymorphisms and suicidal behaviour in people living with HIV treated with efavirenz-containing combination antiretroviral therapy: a global case\u2013control study"],"prefix":"10.3389","volume":"17","author":[{"given":"Alejandro","family":"Arenas-Pinto","sequence":"first","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, University College London","place":["London, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline","family":"Nordwall","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dianne","family":"Carey","sequence":"additional","affiliation":[{"name":"University of New South Wales, Kirby Institute","place":["Sydney, NSW, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney V.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center, College of Pharmacy","place":["Omaha, NE, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D.","family":"Badley","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Department on Molecular Medicine","place":["Rochester, MN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Thompson","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cavan","family":"Reilly","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra E.","family":"Safo","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Grund","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, University of Minnesota","place":["Minneapolis, MN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Lundgren","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Health, Immunity, and Infections, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1093\/cid\/ciy051","article-title":"Risk of suicidal behavior with use of efavirenz: results from the strategic timing of antiretroviral treatment trial","volume":"67","author":"Arenas-Pinto","year":"2018","journal-title":"Clin. 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