Pharmacokinetics of raltegravir in the semen of HIV-infected men.

Background: We sought to determine the pharmacokinetic disposition of raltegravir in the blood and seminal plasma of HIV-infected men. Methods: We conducted a pharmacokinetic study using a staggered sampling approach. 16 HIV-infected men receiving raltegravir-based therapy were recruited into the study. Each participant provided six blood plasma and six seminal plasma samples for quantification of drug concentrations in both compartments. Blood and semen samples were obtained within 1 hour of each other, and were collected prior to the morning dose, and at 1, 2, 4, 8 and 12 hours post-ingestion. Drug concentrations were determined by liquid chromatography tandem mass spectrometry. Results: A total of 96 semen samples and 96 blood samples were obtained from all participants during the study period. The median age and baseline CD4+ cell count of the study participants were 48 years (interquartile range 42 to 53 years) and 450 cells/mm (interquartile range 289 cells/mm to 585 cells/mm). Virologic suppression to < 50 copies/mL had been maintained for a median of 21 months (interquartile range 7 to 35 months) at the time of study enrolment. The median seminal plasma to blood plasma ratios and AUC0-12h seminal plasma to blood plasma ratios of raltegravir were 3.25 (interquartile range 1.46 to 5.37) and 2.26 (interquartile range 1.05 to 4.45), respectively. Conclusions: Concentrations of raltegravir in seminal plasma are several foldhigher than those attained in blood plasma and those required to inhibit viral Publication: Antiviral Therapy; Type: Short communication DOI: 10.3851/IMP2750 replication in this compartment. Further research examining the therapeutic and prophylactic implications of these findings is warranted. Accepted 27 January 2014, published online 12 February 2014 Running head: Raltegravir levels in semen