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Baboon Bone-Marrow Xenotransplant in a Patient with Advanced HIV Disease: Case Report and 8-Year Follow-Up

Michaels, Marian G.1; Kaufman, Christina2; Volberding, Paul A.3; Gupta, Phalguni1; Switzer, William M.4; Heneine, Walid4; Sandstrom, Paul5; Kaplan, Lawrence6; Swift, Patrick7; Damon, Lloyd6; Ildstad, Suzanne T.2,8

Immunobiology

Background. Xenotransplantation offers a solution to the shortage of organ donors and may offer resistance to human-specific pathogens. Baboons are resistant to productive infection with HIV-1. A baboon bone-marrow transplant (BMT) was performed in an attempt to reconstitute the immune system of a patient with advanced AIDS. The aims of this pilot study were to evaluate the safety of the procedure and develop an approach to prevent and monitor for xenozoonoses.

Methods. A source animal was selected on the basis of infectious disease surveillance protocols. Baboon bone marrow, engineered to remove graft-versus-host-disease-producing mature lineages, but to retain hematopoietic stem cells and facilitating cells, was infused into the patient after nonmyeloablative conditioning. Serial clinical, virologic, immunologic, and hematologic evaluations were performed.

Results. A 38-year-old male with advanced AIDS, who had failed to respond to triple-drug antiretroviral therapy, underwent baboon BMT in 1995. The patient tolerated the procedure without complication. Baboon cells were detected in the peripheral blood on days 5 and 13 after transplantation. Baboon endogenous virus (BaEV) was detected on day 5 but not subsequently. Antibody to BaEV was not detected. HIV-1 viral load declined 1.5 log and remained low until 11 months. The patient improved clinically, and no adverse events occurred. The patient is alive 8 years after the procedure.

Conclusions. Baboon BMT to treat AIDS was attempted using nonmyeloablative conditioning and resulted in transient microchimerism and clinical and virologic improvements. Long-term improvement was not achieved; however, no adverse events occurred, and no evidence of transmission of xenogeneic infections was found.

1 University of Pittsburgh, School of Medicine, Pittsburgh, PA.

2 Institute for Cellular Therapeutics, University of Louisville, Louisville, KY.

3 University of California, San Francisco and San Francisco General Hospital, San Francisco, CA.

4 HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, Center for Disease Control and Prevention (CDC), Atlanta, GA.

5 National HIV and Retrovirology Laboratories, Health Canada, Ottawa, Canada.

6 Hematology and Oncology Division, University of California San Francisco, San Francisco, CA.

7 Alta Bates Comprehensive Cancer Center, Radiation Oncology, Berkeley, CA.

This research was carried out in the General Clinical Research Center at San Francisco General Hospital with support from the National Center for Research Resources, National Institutes of Health (RROO083–84), AIDS Clinical Research Center, San Francisco, California, the Center for AIDS Research, University of California San Francisco, P30 AI 27763–11, NIH K08 AI 01437–03, and Project Inform.

8 Address Correspondence to: Dr. Suzanne T. Ildstad, Director, Institute for Cellular Therapeutics Jewish Hospital Distinguished Professor of Transplantation, Professor of Surgery, University of Louisville, Baxter I Biomedical Research Building, 570 South Preston Street, Suite 404, Louisville, KY 40202–1760. E-mail: stilds01@louisville.edu.

Received 11 February 2004. Accepted 10 June 2004.

© 2004 Lippincott Williams & Wilkins, Inc.