Genetic variation on dolutegravir pharmacokinetics and relation to safety and efficacy outcomes: a systematic review.

Background: Dolutegravir (DTG) is an antiviral agent used for the treatment of HIV, however, there is uncertainty over the influence of genetic variation on DTG exposure, and whether it has clinical implications for the efficacy or toxicity in different populations. This systematic review aims to create an overview of the impact of pharmacogenomics (PGx) on DTG exposure, efficacy, and toxicity.

Methods: Publications up to 14 November 2023 were searched and articles were selected on the following criteria: original research articles providing data on people with HIV, data on PGx and either PK or PD or both PD and PGx.

Results: 711 records were identified, and after screening 10 articles were included. Commonly analyzed genes across the articles were UGT1A1, ABCB1, ABCG2, and NR1I2. The most reported variant associated with PD variability was in SLC22A2, with carriers at higher risk of neuropsychiatric adverse events.

Conclusions: This review concludes that while PGx testing may help explain some variability in DTG pharmacokinetics when combined with therapeutic drug monitoring (TDM), current evidence is insufficient to support its routine clinical use. The role of PGx research for DTG remains relevant, especially in specific patient populations where interindividual PK variations are still unexplained.