: 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.

Cusato, J., Borghetti, A., Teti, E., Milesi, M., Tettoni, M. C., Bonora, S., Trunfio, M., D'Avolio, A., Compagno, M., Di Giambenedetto, S., Di Perri, G., Calcagno, A., Dolutegravir Discontinuation for Neuropsychiatric Symptoms in People Living with HIV and Their Outcomes after Treatment Change: A Pharmacogenetic Study, <<METABOLITES>>, 2022; 12 (12): 1-11. [doi:10.3390/metabo12121202] [https://hdl.handle.net/10807/227369]

Dolutegravir Discontinuation for Neuropsychiatric Symptoms in People Living with HIV and Their Outcomes after Treatment Change: A Pharmacogenetic Study

Borghetti, Alberto;D'Avolio, Antonio;Di Giambenedetto, Simona;
2022

Abstract

: 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.
2022
Inglese
Cusato, J., Borghetti, A., Teti, E., Milesi, M., Tettoni, M. C., Bonora, S., Trunfio, M., D'Avolio, A., Compagno, M., Di Giambenedetto, S., Di Perri, G., Calcagno, A., Dolutegravir Discontinuation for Neuropsychiatric Symptoms in People Living with HIV and Their Outcomes after Treatment Change: A Pharmacogenetic Study, <<METABOLITES>>, 2022; 12 (12): 1-11. [doi:10.3390/metabo12121202] [https://hdl.handle.net/10807/227369]
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