Dolutegravir and Risk of Neuropsychiatric Adverse Events: A Pharmacogenetic Study

Dolutegravir (DTG) treatment can lead to neuropsychiatric adverse events (NPAEs). This study assessed the association between NPAEs and polymorphisms in DTG-related pharmacogenes, determined by next-generation sequencing panel testing. Using a case-control design, 36 patients having previously discontinued DTG due to NPAEs were compared to 98 patients tolerating DTG. In the latter group, psychometric scores were compared according to genotype, targeting polymorphisms associated with drug intolerance. NR1I2 c.-22-7659C > T was independently associated with a reduced risk of NPAE-related DTG discontinuation (odds ratio, 0.36 [95% confidence interval, .15-.88] for T-variant allele carriage) and was linked to decreased anxiety scores in control group participants.