{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T23:58:26Z","timestamp":1789257506456,"version":"build-2803163510"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T00:00:00Z","timestamp":1686614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Concerns have been raised regarding neuropsychiatric adverse drug reactions of integrase inhibitors (INSTIs) in patients living with HIV. The aim of this study was to assess the risk of depression and suicidality reporting with INSTIs based on a global pharmacovigilance database.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Depression and suicidality cases in patients treated with INSTIs were identified within the WHO global database of individual case safety reports, VigiBase. Risk of depression and suicidality reporting with INSTIs compared with other ART was assessed using disproportionality analyses (case\/non-case statistical approach).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 19\u200a991\u200a410 reports over the study period, 124\u200a184 reports concerned patients exposed to ART, including 22\u200a661 patients exposed to an INSTI. Among patients treated with an INSTI, 547 cases of depression and 357 cases of suicidality were identified. Disproportionality analyses showed that depression [reporting OR (ROR) 3.6; 95% CI: 3.2\u20134.0] and suicidality (ROR 4.7; 95% CI: 4.1\u20135.4) were more reported with the use of INSTIs compared with other ART. Amongst INSTIs, depression reporting was significantly greater for bictegravir and dolutegravir, whereas suicidality reporting was significantly greater for dolutegravir only.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings suggest that depression and suicidality are adverse drug reactions of all INSTI agents, especially dolutegravir, which may occur within the first months of therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad187","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T21:27:53Z","timestamp":1686691673000},"page":"1944-1947","source":"Crossref","is-referenced-by-count":11,"title":["Association of depression and suicidal behaviour reporting with HIV integrase inhibitors: a global pharmacovigilance study"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3141-5925","authenticated-orcid":false,"given":"Laure-H\u00e9l\u00e8ne","family":"Pr\u00e9ta","sequence":"first","affiliation":[{"name":"Centre R\u00e9gional de Pharmacovigilance, Service de Pharmacologie p\u00e9rinatale p\u00e9diatrique et adulte, H\u00f4pital Cochin, AP-HP, Centre\u2014Universit\u00e9 Paris Cit\u00e9 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Chroboczek","sequence":"additional","affiliation":[{"name":"Service de Maladies Infectieuses et Tropicales, Centre Hospitalier Alpes L\u00e9man , Contamine sur Arve , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Treluyer","sequence":"additional","affiliation":[{"name":"Centre R\u00e9gional de Pharmacovigilance, Service de Pharmacologie p\u00e9rinatale p\u00e9diatrique et adulte, H\u00f4pital Cochin, AP-HP, Centre\u2014Universit\u00e9 Paris Cit\u00e9 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-3571","authenticated-orcid":false,"given":"Laurent","family":"Chouchana","sequence":"additional","affiliation":[{"name":"Centre R\u00e9gional de Pharmacovigilance, Service de Pharmacologie p\u00e9rinatale p\u00e9diatrique et adulte, H\u00f4pital Cochin, AP-HP, Centre\u2014Universit\u00e9 Paris Cit\u00e9 , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,13]]},"reference":[{"key":"2023080202261524100_dkad187-B1","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1007\/s11920-014-0530-4","article-title":"Depression in HIV infected patients: a review","volume":"17","author":"Nanni","year":"2015","journal-title":"Curr Psychiatry Rep"},{"key":"2023080202261524100_dkad187-B2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jad.2021.05.064","article-title":"Prevalence of suicidal ideation, suicide attempt, and suicide plan among HIV\/AIDS: a systematic review and meta-analysis","volume":"292","author":"Pei","year":"2021","journal-title":"J Affect Disord"},{"key":"2023080202261524100_dkad187-B3","doi-asserted-by":"crossref","first-page":"e58","DOI":"10.1111\/hiv.12538","article-title":"Severe depression as a neuropsychiatric side effect induced by dolutegravir","volume":"19","author":"Scheper","year":"2018","journal-title":"HIV Med"},{"key":"2023080202261524100_dkad187-B4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s15010-018-1201-x","article-title":"Overdose of elvitegravir\/cobicistat\/emtricitabine\/tenofovir alafenamide in an HIV-1-infected subject with attempted suicide","volume":"47","author":"\u00c1lvarez","year":"2019","journal-title":"Infection"},{"key":"2023080202261524100_dkad187-B5","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1097\/QAD.0b013e32830e0169","article-title":"Exacerbation of depression associated with starting raltegravir: a report of four cases","volume":"22","author":"Harris","year":"2008","journal-title":"AIDS"},{"key":"2023080202261524100_dkad187-B6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.2169\/internalmedicine.3498-19","article-title":"An HIV-infected patient with no serious adverse events after overdosing on raltegravir","volume":"59","author":"Hosoda","year":"2020","journal-title":"Intern Med"},{"key":"2023080202261524100_dkad187-B7","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1007\/s40506-019-00203-7","article-title":"Update on adverse effects of HIV integrase inhibitors","volume":"11","author":"Kolakowska","year":"2019","journal-title":"Curr Treat Options Infect Dis"},{"key":"2023080202261524100_dkad187-B8","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1111\/j.1365-2125.2011.04037.x","article-title":"Benefits and strengths of the disproportionality analysis for identification of adverse drug reactions in a pharmacovigilance database","volume":"72","author":"Montastruc","year":"2011","journal-title":"Br J Clin Pharmacol"},{"key":"2023080202261524100_dkad187-B9","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/pds.1001","article-title":"The reporting odds ratio and its advantages over the proportional reporting ratio","volume":"13","author":"Rothman","year":"2004","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2023080202261524100_dkad187-B10","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1111\/hiv.13268","article-title":"Major revision version 11.0 of the European AIDS Clinical Society guidelines 2021","volume":"23","author":"Ryom","year":"2022","journal-title":"HIV Med"},{"key":"2023080202261524100_dkad187-B11","volume-title":"Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring: Recommendations for a Public Health Approach, 2021 Update","author":"WHO","year":"2021"},{"key":"2023080202261524100_dkad187-B12","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1097\/PSY.0000000000001127","article-title":"Suicidality among people living with HIV from 2010 to 2021: a systematic review and a meta-regression","volume":"84","author":"Tsai","year":"2022","journal-title":"Psychosom Med"},{"key":"2023080202261524100_dkad187-B13","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1097\/QAI.0000000000002466","article-title":"Long-acting injectable cabotegravir + rilpivirine for HIV maintenance therapy: week 48 pooled analysis of phase 3 ATLAS and FLAIR trials","volume":"85","author":"Rizzardini","year":"2020","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2023080202261524100_dkad187-B14","first-page":"14","article-title":"Dolutegravir neuropsychiatric adverse events: specific drug effect or class effect","volume":"20","author":"Yombi","year":"2018","journal-title":"AIDS Rev"},{"key":"2023080202261524100_dkad187-B15","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s40262-014-0171-0","article-title":"Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system","volume":"53","author":"Calcagno","year":"2014","journal-title":"Clin Pharmacokinet"},{"key":"2023080202261524100_dkad187-B16","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1124\/dmd.112.048918","article-title":"In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor","volume":"41","author":"Reese","year":"2013","journal-title":"Drug Metab Dispos"},{"key":"2023080202261524100_dkad187-B17","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1080\/00498254.2018.1539278","article-title":"Antiretroviral concentrations and surrogate measures of efficacy in the brain tissue and CSF of preclinical species","volume":"49","author":"Srinivas","year":"2019","journal-title":"Xenobiotica"},{"key":"2023080202261524100_dkad187-B18","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1097\/QAD.0000000000002628","article-title":"Antiretroviral drug concentrations in brain tissue of adult decedents","volume":"34","author":"Ferrara","year":"2020","journal-title":"AIDS"},{"key":"2023080202261524100_dkad187-B19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.tips.2009.10.001","article-title":"The complexities of antiretroviral drug\u2013drug interactions: role of ABC and SLC transporters","volume":"31","author":"Kis","year":"2010","journal-title":"Trends Pharmacol Sci"},{"key":"2023080202261524100_dkad187-B20","doi-asserted-by":"crossref","first-page":"4","DOI":"10.24875\/AIDSRev.19000023","article-title":"Neuropsychiatric adverse events with dolutegravir and other integrase strand transfer inhibitors","volume":"21","author":"Hoffmann","year":"2019","journal-title":"AIDS Rev"},{"key":"2023080202261524100_dkad187-B21","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jclinepi.2021.01.015","article-title":"Adverse drug reaction risks obtained from meta-analyses and pharmacovigilance disproportionality analyses are correlated in most cases","volume":"134","author":"Khouri","year":"2021","journal-title":"J Clin Epidemiol"},{"key":"2023080202261524100_dkad187-B22","article-title":"Variables associated with neuropsychiatric symptoms in PLWH receiving dolutegravir-based therapy in phase III clinical trials","author":"van Wyk"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/8\/1944\/50967424\/dkad187.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/8\/1944\/50967424\/dkad187.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T02:27:57Z","timestamp":1690943277000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/78\/8\/1944\/7197288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,13]]},"references-count":22,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,6,13]]},"published-print":{"date-parts":[[2023,8,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkad187","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,8]]},"published":{"date-parts":[[2023,6,13]]}}}