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HIV/AIDS Vertical Transmission: Fetal peripheral blood cells efficiently metabolize AZT

AIDSWEEKLY Plus; Monday, June 9, 2003
Staff Medical Writers


NewsRx -- Fetal peripheral blood cells efficiently metabolize the antiretroviral agent zidovudine, better known as AZT.

In a recent study, researchers in Israel "compared the phosphorylation rate of 3'-azidothymidine (AZT) in isolated maternal and fetal peripheral blood mononuclear cells (PBMCs) with that in amniocytes obtained during gestation and at term."

"Maternal PBMCs were isolated from venous blood samples obtained from HIV-seronegative pregnant women during delivery. Immediately after delivery, cord blood specimens were collected, and fetal PBMCs were isolated," according to R. Agbaria and coauthors at Ben Gurion University of the Negev. "In a separate set of experiments, maternal and fetal PBMCs and amniocytes were obtained at 17-21 weeks of gestation."

In these experiments, "the fresh isolated PBMCs and amniocytes were maintained in RPMI 1640 medium until incubation with 10 microM tritiated AZT (10 microCi/mL)," they noted. "Thereafter, methanolic cell extracts were prepared for determination of AZT phosphates by high-performance liquid chromatography."

"Fetal PBMCs can efficiently convert AZT to its antivirally active metabolite," test results revealed. "There were no significant differences after six or 12 hours of incubation with AZT between AZT phosphate levels in maternal and fetal PBMCs isolated at term or at 17-21 weeks of gestation: AZT monophosphate was found to be the major metabolite (about 95%). AZT phosphate levels in the amniocytes were up to sevenfold higher than those in the maternal or fetal PBMCs."

"These results show that during pregnancy and at term, fetal PBMCs-like maternal PBMCs-are able to take up AZT and to efficiently generate the active metabolite AZT triphosphate," the researchers concluded. "These results are of major significance both in enabling efficient treatment of the fetuses of HIV-infected women and in the prediction and understanding of the efficacy and toxicity of AZT in pregnant women and their fetuses."

Agbaria and colleagues published their findings in the Journal of Acquired Immune Deficiency Syndromes (Phosphorylation of 3'-azidothymidine in maternal and fetal peripheral blood mononuclear cells during gestation and at term. J Acquir Immune Defic Syndr. 2003 Apr 15;32(5):477-81.

Additional information can be obtained by contacting R. Agbaria, Ben Gurion University of the Negev, Department of Clinical Pharmacology, Faculty of Health Science, IL-84105 Beer Sheva, Israel.

The publisher of the Journal of Acquired Immune Deficiency Syndromes can be contacted at: Lippincott Williams & Wilkins, 530 Walnut St., Philadelphia, PA 19106-3621, USA.

The information in this article comes under the major subject areas of AIDS and HIV, Fetal Medicine and Women's Health.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Agbaria R, Manor E, Barak J, et al., "Phosphorylation of 3'-azidothymidine in maternal and fetal peripheral blood mononuclear cells during gestation and at term", J Acquir Immune Defic Syndr. 2003 Apr 15;32(5):477-81.

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