The purposes of this study are to determine whether transporters expression levels and drug interaction between TDF and FTC could contribute to modulate the placental transfer of this drug or. To test this hypothesis, an ex vivo model known as "the perfused ex vivo cotyledon model" allows to reproduce the conditions of the third trimester of pregnancy
Nowadays, mother-to-child HIV transmission is the main cause of paediatric HIV infections. Yet, this way of transmission is effectively limited by the use of antiretroviral therapies during pregnancy in HIV infected women. The study TEmAA (ANRS 12109) we conducted allowed us to suggest a therapeutic scheme of administration of the association tenofovir disoproxil fumarate (TDF) - emtricitabine (FTC) to reduce the risk of postpartum resistance that may occur with the administration of a single dose of nevirapine before delivery. However, we also observed a large interindividual variability of TDF in vivo placental transfer that remained unexplained. Placental membrane transporters, including efflux transporters belonging the ABC transporter superfamily and uptake transporters, may constitute a source of variability. In this case, we showed such an association for maraviroc with a significant inverse correlation between its clearance index and the placental expression level of several efflux transporters of the ABCC/MRP family. Regarding TDF, it has been shown that this drug is a substrate of several efflux transporters (ABCC2/MRP2, ABCC4/MRP4, ABCC10/MRP7) and an uptake transporter (hOAT3). As these transporters are expressed on the placental barrier, it may be hypothesized that their expression levels could contribute to modulate the placental transfer of this drug. To test this hypothesis, an ex vivo model known as "the perfused ex vivo cotyledon model" allows to reproduce the conditions of the third trimester of pregnancy. Our first aim is to evaluate the potential effect of ABCC2, ABCC4, ABCC10 and hOAT3 placental expression on TDF placental transfer (First year). We also want to investigate whether a potential interaction between TDF and FTC could take part to variability.
Study Type
OBSERVATIONAL
Enrollment
369
Maternité de Port Royal
Paris, France
Determination of ABC transporters gene expression levels by quantitative RT-PCR
Placental villi were extracted To study the expression level of transporters that may affect the placental transfer. Gene expression was evaluated for each sample using the cycle threshold value (CT), defined as the fraction cycle number at which the fluorescence generated by SYBR green dye-amplicon complex formation passes a fixed threshold above the baseline.
Time frame: 1 hour
Fetal transfer rate (%)of emtricitabine alone, or Tenofovir alone, or in association
Placental perfusion with Emtricitabine alone, then with Tenofovir alone, and together. Fetal transfer rate of (FTR) was calculated as follow : (Cf\*Vf)\*100/ ((Cf\*Vf)+(Cm\*Vm))where Cf denotes the fetal concentration, Vf, the volume of fetal perfusate, Cm, the maternal concentration and Vm, the volume maternal perfusate.
Time frame: 3 hours
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