Background:  Antiretrovirals (ARV) and elective caesarean contribute to reduce mother-to-child transmission rate which remains the dominant cause of child contamination. During pregnancy, the management of ARV implies to take into account the benefit-risk assessment of drugs for both mothers and fetus. Many ARV are transported by membrane transporters such as P-glycoprotein (MDR1) and multidrug-resistance associated protein (MRP1) which are expressed by placental cytotrophoblasts. Informations are missing regarding their expression in placentas during HIV-infection and their influence on the materno-fetal transfer of ARV during pregnancy. Therefore, we aimed to compare levels of expression of MDR1 and MRP1 transcripts, encoding those drug transporters, in placentas from HIV⁺ and HIV^- women.

Methods: In this prospective study, 25 HIV⁺ and 28 HIV^- women were enrolled. Chorionic villi were isolated by microdissection from placentas obtained immediately after delivery. The number of copies of MDR1 and MRP1 transcripts /µg cDNA was assessed by quantitative real-time PCR. Data between groups were compared by Mann-Whitney non-parametric test and/or ANOVA as appropriate and correlations were assessed by Spearman rank-test.

Results: Women from both groups were comparable according to their mean age and the week of delivery. Median MDR1 expression in placentas from HIVp women was significantly higher compared to HIV^- women: 6188 (range 1487 to 71,705) and 1902 (79 to 8962) copies/µg cDNA respectively (p <0.0002). No correlation was found between MDR1 expression and the viral load nor CD4⁺ cell count. However our findings pointed out the influence of ARV regimen on MDR1 expression (p = 0.0008). The level of expression of MDR1 was similar in HIV^- and HIV⁺ women treated by zidovudine + lamivudine or zidovudine + lamivudine + nelfinavir combination, and significantly lower than in HIV⁺ women treated by zidovudine alone (p <0.005). Although there was a trend of correlation between MDR1 and MRP1 levels among HIV^- women (s = 0.36, p = 0.07), median MRP1 expression was not statistically different between the 2 groups (6904 in HIV⁺ and 6581 in HIV^- women).

Conclusions:  In HIV⁺ women, the up-regulation of MDR1 expression contrary to MRP1 certainly contributes to affect the materno-fetal transfer of ARV across the placental barrier. Thus, in this population, a better protection of the fetus might be provided against ARV exposure and against viral replication.

Keywords: placenta; MDR1; MRP1