{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:58:25Z","timestamp":1777532305414,"version":"3.51.4"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,17]],"date-time":"2023-12-17T00:00:00Z","timestamp":1702771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate whether efavirenz (EFV) or 8\u2010hydroxy\u2010EFV (8\u2010OH\u2010EFV) plasma levels are associated with neurocognitive impairment and central nervous system (CNS) side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a cross\u2010sectional analysis to explore the potential links between EFV\/8\u2010OH\u2010EFV levels and cognitive performance or CNS\u2010related side effects in patients screened within a randomized trial involving a switch from EFV to rilpivirine. The Mann\u2013Whitney test was employed to compare drug levels in patients with or without cognitive impairment, depression, anxiety, sleep disorder or CNS symptoms. Additionally, Spearman's test was used to assess correlations between drug levels and test scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 104 patients, neither EFV nor 8\u2010OH\u2010EFV levels were linked to cognitive impairment, although trends towards higher EFV levels were observed in those with impaired executive function (<jats:italic>p<\/jats:italic>\u2009=\u20090.055) and language performances (<jats:italic>p<\/jats:italic>\u2009=\u20090.021). On the other hand, elevated 8\u2010OH\u2010EFV levels, but not EFV levels, were associated with more CNS side effects (222 vs. 151\u2009ng\/mL, <jats:italic>p<\/jats:italic>\u2009=\u20090.027), depressive symptoms (247 vs. 164\u2009ng\/mL, <jats:italic>p<\/jats:italic>\u2009=\u20090.067) and sleep impairment (247 vs. 164\u2009ng\/mL, <jats:italic>p<\/jats:italic>\u2009=\u20090.078). Consistently, a trend towards a correlation between EFV levels and lower <jats:italic>z<\/jats:italic>\u2010scores in executive function and motor function was observed, while 8\u2010OH\u2010EFV levels, but not EFV levels, were directly correlated with symptom scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Higher levels of 8\u2010OH\u2010EFV were associated with CNS side effects, while EFV levels were only marginally associated with cognitive performance, thus suggesting that EFV and its metabolite may act differently in determining detrimental neurological effects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hiv.13600","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:41:21Z","timestamp":1702860081000},"page":"491-497","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Influence of efavirenz and 8\u2010hydroxy\u2010efavirenz plasma levels on cognition and central nervous system side effects"],"prefix":"10.1111","volume":"25","author":[{"given":"Alice","family":"Ranzani","sequence":"first","affiliation":[{"name":"Fondazione IRCCS \u201cSan Gerardo dei Tintori\u201d  Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Castelli","sequence":"additional","affiliation":[{"name":"University of Brescia  Brescia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Di Biagio","sequence":"additional","affiliation":[{"name":"University of Genoa  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0073-1789","authenticated-orcid":false,"given":"Antonella","family":"d'Arminio Monforte","sequence":"additional","affiliation":[{"name":"University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"D'Avolio","sequence":"additional","affiliation":[{"name":"University of Turin  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Soria","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS \u201cSan Gerardo dei Tintori\u201d  Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Bai","sequence":"additional","affiliation":[{"name":"University of Milan  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4395-5379","authenticated-orcid":false,"given":"Emanuele","family":"Foc\u00e0","sequence":"additional","affiliation":[{"name":"University of Brescia  Brescia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6622-6358","authenticated-orcid":false,"given":"Lucia","family":"Taramasso","sequence":"additional","affiliation":[{"name":"University of Genoa  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Calcagno","sequence":"additional","affiliation":[{"name":"University of Turin  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8247-276X","authenticated-orcid":false,"given":"Elena","family":"Bresciani","sequence":"additional","affiliation":[{"name":"University of Milano\u2013Bicocca  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Torsello","sequence":"additional","affiliation":[{"name":"University of Milano\u2013Bicocca  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Bonfanti","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS \u201cSan Gerardo dei Tintori\u201d  Monza Italy"},{"name":"University of Milano\u2013Bicocca  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Lapadula","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS \u201cSan Gerardo dei Tintori\u201d  Monza Italy"},{"name":"University of Milano\u2013Bicocca  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,17]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Consolidated guidelines on HIV prevention testing treatment service delivery and monitoring: recommendations for a public health approach.World Health Organization;2021. 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