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The Role of Transplacental Microtransfusions of Maternal Lymphocytes in In Utero HIV Transmission

Lee, Tzong-Hae MD, PhD*; Chafets, Daniel M BS*; Biggar, Robert J MD†‡; McCune, Joseph M MD, PhD§; Busch, Michael P MD, PhD*‖

JAIDS Journal of Acquired Immune Deficiency Syndromes: October 1st, 2010 - Volume 55 - Issue 2 - p 143-147
doi: 10.1097/QAI.0b013e3181eb301e
Basic and Translational Science

Background: The mechanisms of HIV transmission from mothers to infants are poorly understood. A possible mechanism of in utero transmission is transplacental transfer of HIV-infected maternal leukocytes into the fetal circulation during pregnancy.

Objective: To determine if the frequency of in utero HIV infection correlates with presence or levels of maternal cells (MCs) in placenta-derived cord blood.

Methods: DNA was extracted from dried cord blood spots (DBS) from newborns born to HIV+ mothers and corresponding maternal DBS specimens. Paired mother-infant samples were probed to identify unique maternal sequences targeted by 24 allele-specific real-time polymerase chain reaction assays. Infant DBS-derived DNA was then probed in replicate analyses for noninherited maternal allelic sequences. Rates of detection and levels of MCs in DBS samples of HIV(+) and HIV(−) newborns were compared.

Results: Of 114 mother-infant pairs with informative alleles, 38 newborns were HIV(+) and 76 HIV(−), based on detection of HIV DNA/RNA at birth. MC were detected in 23 of 38 HIV(+) newborns (60.5%) and in 47 of 76 HIV(−) newborns (61.8%). The mean and median concentrations of nucleated MCs in DBS for the HIV(+)/MC(+) newborns (n = 23) were 0.33% and 0.27%, respectively, compared with 0.09% and 0.10% for the HIV(−)/MC(+) newborns (n = 47) (2-sample T test for means: P = 0.78).

Conclusions: There was no significant difference in rates of detection or concentrations of MC in DBS between HIV(+) and HIV(−) newborns. Therefore, we could not demonstrate a correlation between MC in DBS, assumed to reflect levels of in utero maternal-fetal cell trafficking, and the risk of in utero HIV transmission.

From the *Blood Systems Research Institute, San Francisco, CA; †Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; ‡Department of Epidemiology Research, State Serum Institute, Copenhagen, Denmark; §Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA; and ‖Department of Laboratory Medicine, University of California, San Francisco, CA.

Received for publication April 26, 2010; accepted May 27, 2010.

These studies were supported in part by R01-HL-083388, NHLBI (D.M.C., T.H.L., and M.B.), R37 AI40312, and DPI OD00329 (J.M.M.). J.M.M. is a recipient of the NIH Director's Pioneer Award Program, part of the NIH Roadmap for Medical Research.

*Drs. J.M.M. and M.P.B. contributed equally to the design, funding, and oversight of this study.

Correspondence to: Michael P. Busch, MD, PhD, Director, Blood Systems Research Institute, Vice President, Research/Scientific Affairs, Blood Systems, Prof Laboratory Medicine, UCSF, 270 Masonic Avenue, San Francisco CA 94118 (e-mail: mbusch@bloodsystems.org).

© 2010 Lippincott Williams & Wilkins, Inc.