AbstractThe aim of this study was to evaluate the effect of UGT1A1 polymorphisms on Raltegravir (RAL) and its metabolite RAL-glucuronide trough plasma concentrations ([RAL]plasma and [RAL-glu]plasma) and on the metabolic ratio (MR): [RAL-glu]plasma/[RAL]plasma. UGT1A1 genotyping was performed on 96 patients. 44% (n = 42) were homozygous UGT1A1*1/*1 while 50% (n = 48) and 6% (n = 6) were UGT1A1*28 and UGT1A1*36 carriers, respectively. The median concentration and interquartile range (IQR) of [RAL]plasma were 88.5 ng/ml (41.0–236), 168 ng/ml (85.8–318) and 92.5 ng/ml (36.4–316) for UGT1A1*1/*1, UGT1A1*28 and UGT1A1*36 carriers, respectively. Only the difference between UGT1A1*1/*1 and *28 carriers was statistically significant (p = 0.022). The median MR (IQR) were 5.8 (3–10), 2.9 (1.6–5.3) and 3.2 (1.7–5.9) for UGT1A1*1/*1, UGT1A1*28 and UGT1A1*36 carriers, respectively. Only the difference between UGT1A1*1/*1 and *28 carriers was statistically significant (p = 0.004) with an allele-dependent effect: UGT1A1*28 homozygous having lower MR than heterozygous carriers who show lower MR compared to *1/*1. Except for the sensation of fatigue, this PK effect did not correlate with clinical adverse events or biological abnormalities. In Conclusion, we demonstrate that UGT1A1*28 polymorphism has a significant impact on RAL metabolism: UGT1A1*28 carriers being characterized by higher [RAL]plasma and lower MR.