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Role of HIV and Antiretroviral Therapy on the Expression of Placental Transporters in Women with HIV

  • Research Article
  • Theme: Celebrating Women in the Pharmaceutical Sciences
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Abstract

Treatment guidelines recommend continuation of combination antiretroviral therapy (cART) throughout pregnancy for all women living with human immunodeficiency virus (HIV). Many of these drugs are substrates of transporters expressed in the placenta and therefore play a role in fetal exposure. As placental transporters can be impacted by both HIV infection and drug therapy, our objective was to explore the impact of HIV infection and cART on transporter expression. Drug transporter expression was examined in human placental samples collected from women with HIV (n = 25) and from healthy HIV(−) controls (n = 23). The effect of exposure to drugs commonly used in cART during pregnancy was examined in vitro in placental villous explants obtained from healthy women. Gene expression was measured via qRT-PCR. Several ABC (ABCG2, ABCC1,2,4) and SLC (SLC21A9, SLC22A1,3,11) transporters were significantly downregulated in placentas isolated from HIV(+) women as compared with HIV(−) controls (p < 0.05–0.001), while ABCB1 and SLC21A12 were significantly upregulated (p < 0.001). Twenty-four to 48-h exposure of human placental explants to agents used in cART resulted in significant upregulation of ABCB1 and downregulation of SLC22A11. Our findings suggest that transplacental transport may be compromised during HIV infection due to altered expression of clinically important transporters. Furthermore, in vitro results indicate that cART imposes significant alterations in placental transporters but not all changes are consistent with findings in the placenta from HIV(+) women, indicating disease effects. As this may impact in utero-fetal exposure to clinically used medications, further studies are needed to determine the overall impact on maternal-fetal transfer.

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Funding

This work was supported by operating grants from the Canadian Institutes of Health Research [MOP 13346, MOP-130398, PJT-148684]. D.K was a recipient of an Ontario Graduate Scholarship.

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Authors and Affiliations

  1. Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario, M5S 3M2, Canada

    Dea Kojovic & Micheline Piquette-Miller

  2. Pharmacy Practice Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia

    Ragia H. Ghoneim

  3. Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada

    Lena Serghides

  4. Department of Immunology and Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

    Lena Serghides

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  1. Dea Kojovic
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  4. Micheline Piquette-Miller
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Correspondence to Micheline Piquette-Miller.

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Conflict of Interest

Micheline Piquette-Miller, Ragia H Ghoneim, and Dea Kojovic have no conflicts of interest to disclose pertaining to this project. Lena Serghides reports personal fees from ViiV Healthcare for participation in a Women and Transgender Think Tank.

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Kojovic, D., Ghoneim, R.H., Serghides, L. et al. Role of HIV and Antiretroviral Therapy on the Expression of Placental Transporters in Women with HIV. AAPS J 22, 138 (2020). https://doi.org/10.1208/s12248-020-00516-2

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