Dolutegravir and Risk of Neuropsychiatric Adverse Events: a Pharmacogenetic Study

Abstract

Dolutegravir treatment can lead to neuropsychiatric adverse events (NPAE). This study assessed the association between NPAE and polymorphisms in dolutegravir-related pharmacogenes, determined by next-generation sequencing panel testing. Using a case-control design, 36 patients having previously discontinued dolutegravir due to NPAE were compared to 98 patients tolerating dolutegravir. 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 dolutegravir discontinuation (odds ratio of 0.36 [95% confidence interval, .15–.88] for T-variant allele carriage) and was linked to decreased anxiety scores in control-group participants.