HIV-Resistant Stem Cells Engrafted to Treat AIDS-Related Lymphoma

By Anthony J. Brown, MD

NEW YORK DEC 08, 2008 (Reuters Health) - Anti-HIV genes can be introduced into autologous peripheral blood progenitor cells, resulting in a potentially HIV-resistant treatment for AIDS-related lymphoma (ARL), according to study findings presented Sunday at the American Society of Hematology annual meeting in San Francisco.

"We are the first study to incorporate multiple genes into hematopoietic stem cells collected from the patient for the treatment of their HIV infection," lead author Dr. Amrita Krishnan told Reuters Health. "In addition, we are the first to use a lentiviral vector for the transfer of the genes into the stem cells for AIDS and, even more importantly, this is the first in-human use of this mechanism of using a short-hairpin RNA trigger for RNA interference in any disease."

Autologous stem cell transplantation is viable treatment for relapsed or high risk ARL. Although treatment-related mortality in ARL patients is comparable to that seen in HIV-negative lymphoma patients, optimal outcomes are hampered by the presence of HIV.

Highly active antiretroviral therapy can achieve undetectable HIV levels in the blood, but HIV tissue reservoirs and resistance to HAART may still impair outcomes. These issues, however, could be circumvented if it were possible to make the stem cells intrinsically resistant to HIV.

To do that, Dr. Krishnan, from the City of Hope National Medical Center, Duarte, California, and colleagues used a lentiviral vector to incorporate short hairpin RNA to HIV tat/rev, a nucleolar localizing TAR decoy sequence, and a ribozyme targeted to CCR5 into the peripheral blood progenitor cells of four patients with ARL.

The results indicate that following high-dose chemotherapy, stable engraftment of these autologous, anti-HIV cells was possible. No serious adverse events were noted.

Dr. Krishnan said that further research is needed to examine how to improve engraftment and whether engraftment of cells with less intensive non-marrow-ablative doses of chemotherapy is possible, "which would then allow the use of this procedure in HIV-infected patients without lymphoma."


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