The aim was to describe the blood plasma (BP) and seminal plasma (SP) pharmacokinetics of tenofovir (TFV) in HIV-1 infected men, to assess the role of genetic polymorphism in the variability of TFV transfer into the male genital tract and to evaluate the impact of TFV SP exposure on seminal plasma HIV load (spVL). Men from EVARIST ANRS EP49 study treated with TFV as part of their antiretroviral therapy were included in the study. A total of 248 and 217 TFV BP and SP concentrations from 129 men were available for the analysis. For pharmacogenetic assessment a total of 121 single nucleotide polymorphisms (SNP) were genotyped. Data were analyzed using a non-linear mixed effects modeling approach. TFV pharmacokinetics was best described by a two-compartment model for BP and by an effect compartment with different input and output constants for SP. TFV exposures (AUC0-24) were higher in SP than in BP (median AUC0-24 7.01 vs 2.97 mg.l-1.h, respectively). Median [range] SP-to-BP AUC0-24 ratio was 2.24 [0.53 - 34.13]. After correction for multiple testing, none of the SNPs were significantly associated with TFV transfer rate constant. The impact of TFV SP AUC0-24 or TFV SP-to-BP AUC0-24 ratio on spVL was not significant (p = 0.808 and 0.768, respectively). This is the first population-model describing TFV pharmacokinetics in the male genital tract. TFV SP concentrations were higher than BP concentrations. Despite TFV SP exposures higher than BP exposures, spVL was detectable for 12.2 % of men.
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