{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:54:33Z","timestamp":1781848473407,"version":"3.54.5"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"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":"\n Objective<\/jats:title>\n \n To characterize the distribution of voriconazole (VRC) trough concentrations (\n C<\/jats:italic>\n trough<\/jats:sub>\n ), identify factors associated with VRC exposure in HIV-infected patients complicated by invasive fungal disease (IFD), and determine the\n C<\/jats:italic>\n trough<\/jats:sub>\n threshold associated with an increased risk of adverse drug reactions (ADRs).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A retrospective study was conducted at the First Hospital of Changsha from 1 January 2021, to 31 December 2025. Univariate and multivariate analyses were performed to identify factors associated with VRC\n C<\/jats:italic>\n trough<\/jats:sub>\n . Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for predicting ADRs.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 44 patients contributed 55 VRC\n C<\/jats:italic>\n trough<\/jats:sub>\n measurements. The median\n C<\/jats:italic>\n trough<\/jats:sub>\n was 2.44\u00a0mg\/L (range, 0.07\u20137.26\u00a0mg\/L). Of these measurements, 8 (14.5%) were &lt;1.0\u00a0mg\/L, 39 (70.9%) were within the therapeutic range (1.0\u20135.5\u00a0mg\/L), and 8 (14.5%) were &gt;5.5\u00a0mg\/L. The interindividual coefficient of variation for\n C<\/jats:italic>\n trough<\/jats:sub>\n was 63.6%. Univariate analysis showed that albumin-bilirubin (ALBI) grade, Child\u2013Pugh classification, hypoalbuminemia, concomitant glucocorticoid use, C-reactive protein levels, and CD4\n +<\/jats:sup>\n \/CD8\n +<\/jats:sup>\n ratio were associated with VRC\n C<\/jats:italic>\n trough<\/jats:sub>\n . The mixed-effects model identified ALBI grade, concomitant glucocorticoid use, and the CD4\n +<\/jats:sup>\n \/CD8\n +<\/jats:sup>\n ratio as factors significantly associated with VRC\n C<\/jats:italic>\n trough<\/jats:sub>\n . The incidence of ADRs was 20.5% (9\/44). Patients who developed ADRs had significantly higher median VRC\n C<\/jats:italic>\n trough<\/jats:sub>\n than those who did not (5.15 mg\/L [range, 0.88\u20135.93 mg\/L]\n vs.<\/jats:italic>\n 2.40 mg\/L [range, 0.07\u20137.26 mg\/L],\n P<\/jats:italic>\n = 0.038). ROC analysis yielded an area under the curve (AUC) of 0.720 (95% confidence interval, 0.525\u20130.914;\n P<\/jats:italic>\n = 0.038) for\n C<\/jats:italic>\n trough<\/jats:sub>\n in predicting ADRs. The optimal cutoff value was 4.43\u00a0mg\/L, with a sensitivity of 66.7% and a specificity of 80.4%.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n In patients with HIV-infected and IFD, VRC\n C<\/jats:italic>\n trough<\/jats:sub>\n showed substantial variability and was influenced by multiple factors, including ALBI grade, concomitant glucocorticoid use, and the CD4\n +<\/jats:sup>\n \/CD8\n +<\/jats:sup>\n ratio. Maintaining VRC\n C<\/jats:italic>\n trough<\/jats:sub>\n &lt; 4.43\u00a0mg\/L may help reduce the risk of ADRs in this population.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2026.1837833","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:46:35Z","timestamp":1781847995000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Voriconazole therapeutic drug monitoring and safety in HIV-infected patients with invasive fungal disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Lin","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University","place":["Changsha, Hunan, China"]},{"name":"Department of Pharmacy, The First Hospital of Changsha","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University","place":["Changsha, Hunan, China"]},{"name":"Department of Pharmacy, The First Hospital of Changsha","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University","place":["Changsha, Hunan, China"]},{"name":"Department of Pharmacy, The First Hospital of Changsha","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University","place":["Changsha, Hunan, China"]},{"name":"Department of Pharmacy, The First Hospital of Changsha","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaogui","family":"He","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The First Hospital of Changsha","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s12981-025-00757-1","article-title":"Hypoalbuminemia in HIV-Infected patients: its determinants and correlation with CD4 count in northern Uganda","volume":"22","author":"Ahmed","year":"2025","journal-title":"AIDS Res. 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