Medical Advocates for Social Justice
Conference Abstract
from the
4th International Workshop on the Clinical Pharmacology
of HIV Therapy

Cannes, France  March 27-29, 2003

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Background:
P-glycoprotein is a transmembrane efflux transporter of a large number of pharmacological components including protease ihibitors which are now more frequently administered to HIV-infected women during pregnancy. As P-glycoprotein (P-gp) is expressed in the placenta and localised on the fetal side of trophoblastic cells, it may play an important role in limiting the materno-fetal transfer of antiretroviral drugs. Therefore, we investigated the expression of the P-gp encoding mdr1 gene in placentas from women infected or not by HIV.

Methods:
Ten HIV-infected women gave their informed consent to the use of their placentas in this study. Nine other placentas were obtained from non-infected non-treated women. Total RNA was extracted from isolated chorionic villi using standard procedure. cDNA was synthetised from 1 µg total RNA. Relative quantification of mdr1 transcripts was performed by real time PCR analysis using the SYBR^ÒGreen technology on a LightCycler^Ò (Roche Diagnostics). Each cDNA sample was tested in triplicate and transcripts concentrations were calculated from 5 serial dilutions of cDNA from the positive control K562 R7 cell line. Student t-test was used to compare both populations.

Results:
Our preliminary results showed a mean of 20-fold statistically significant increase in mdr1 transcription in HIV-positive subpopulation compared to non-infected women (p=0.01). Individual ratios of mdr1 overexpression in HIV-infected to the mean of non-infected placentas were comprised between 2.3 and 46.4. These results are currently under investigation upon a larger cohort. This overexpression of mdr1 was observed in a similar extent with placentas from pregnant women treated with zidovudine alone or in combination with nelfinavir.

Conclusion:
This up-regulation of mdr1 in HIV-infected placentas might contribute to diminish the fetal exposure to antiretroviral treatments or to other P-gp substrates and modulate their materno-fetal transport across the placental barrier.

Overexpression of mdr1 in placentas from HIV-infected women.
 4th International Workshop on the Clinical Pharmacology of HIV Therapy
A Medical Advocates for Social Justice Update