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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

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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.

© 2004 Lippincott Williams & Wilkins, Inc.





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