Academic Journal
Dolutegravir Discontinuation for Neuropsychiatric Symptoms in People Living with HIV and Their Outcomes after Treatment Change: A Pharmacogenetic Study
| العنوان: | Dolutegravir Discontinuation for Neuropsychiatric Symptoms in People Living with HIV and Their Outcomes after Treatment Change: A Pharmacogenetic Study |
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| المؤلفون: | Cusato, Jessica, Borghetti, Alberto, Teti, Elisabetta, Milesi, Maurizio, Tettoni, Maria Cristina, Bonora, Stefano, Trunfio, Mattia, D'Avolio, Antonio, Compagno, Mirko, Di Giambenedetto, Simona, Di Perri, Giovanni, Calcagno, Andrea |
| المساهمون: | Cusato, Jessica, Borghetti, Alberto, Teti, Elisabetta, Milesi, Maurizio, Tettoni, Maria Cristina, Bonora, Stefano, Trunfio, Mattia, D'Avolio, Antonio, Compagno, Mirko, Di Giambenedetto, Simona, Di Perri, Giovanni, Calcagno, Andrea |
| سنة النشر: | 2022 |
| المجموعة: | Università degli studi di Torino: AperTo (Archivio Istituzionale ad Accesso Aperto) |
| مصطلحات موضوعية: | depression, discontinuation, dolutegravir, pharmacogenetic, psychiatric symptoms |
| الوصف: | Neuropsychiatric symptoms have been reported in patients receiving dolutegravir, a known inhibitor of the renal and neuronal-expressed organic anion transporter 2 (encoded by SLC22A2 gene). The effect of the genetic variant SLC22A2 808C>A on dolutegravir discontinuation was assessed and analyzed by real-time PCR. We enrolled 627 participants: CA/AA carriers showed a higher prevalence of pre-existing psychiatric comorbidities and use of antidepressants. After 27.9 months, 108 participants discontinued dolutegravir, 64 for neuropsychiatric symptoms. Patients with pre-existing psychiatric comorbidities were at higher risk of dolutegravir discontinuation, while patients carrying the SLC22A2 CA/AA genotype were not. Combining the two variables, an opposite effect of SLC22A2 variants according to pre-existing psychiatric disorders was observed. Using multivariate Cox models, the combined variable pre-existing psychiatric comorbidities/SLC22A2 variants and the use of non-tenofovir alafenamide containing antiretroviral regimens were predictors of dolutegravir discontinuation for neuropsychiatric symptoms. Within 30 days, the majority of participants had a complete resolution of symptoms (61.8%), while 32.7% and 5.5% had partial or no change after dolutegravir discontinuation, respectively. Discontinuation of dolutegravir for neuropsychiatric symptoms was not uncommon and more frequent in participants with pre-existing psychiatric disorders. We described an interaction between SLC22A2 genetic variant and psychiatric comorbidities. In 38.2% of patients, a complete neuropsychiatric symptoms resolution was not observed after dolutegravir discontinuation suggesting the involvement of additional factors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/36557240; volume:12; issue:12; firstpage:1202; lastpage:1212; numberofpages:11; journal:METABOLITES; https://hdl.handle.net/2318/1884160 |
| DOI: | 10.3390/metabo12121202 |
| الاتاحة: | https://hdl.handle.net/2318/1884160 https://doi.org/10.3390/metabo12121202 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.8C7FEFD8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/metabo12121202 |
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