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

AAPS J. 2020 Oct 25;22(6):138. doi: 10.1208/s12248-020-00516-2.

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.

Keywords: HIV; antiretroviral agents; placenta; pregnancy; transporters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacokinetics*
  • Down-Regulation
  • Drug Therapy, Combination
  • Female
  • Gene Expression Profiling
  • HIV Infections / diagnosis
  • HIV Infections / drug therapy*
  • HIV Infections / pathology
  • HIV Infections / transmission
  • HIV-1 / isolation & purification
  • Humans
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control
  • Male
  • Maternal Age
  • Maternal-Fetal Exchange
  • Organic Anion Transporters / metabolism*
  • Placenta / metabolism*
  • Placenta / pathology
  • Pregnancy
  • Pregnancy Complications, Infectious / diagnosis
  • Pregnancy Complications, Infectious / drug therapy*
  • Pregnancy Complications, Infectious / pathology
  • Tissue Culture Techniques
  • Treatment Outcome
  • Up-Regulation
  • Viral Load

Substances

  • ATP-Binding Cassette Transporters
  • Anti-HIV Agents
  • Organic Anion Transporters