AIDSWEEKLY Plus; Monday, August 23, 2004
Staff Medical Writers

"VRX496 is a VSV-G-pseudotyped HIV-based vector that encodes an antisense payload against the HIV envelope gene. The antisense payload is under the control of the native LTR promoter, which is highly transactivated by tat upon HIV infection in the cell," scientists in the United States report.

"Transfer of autologous CD4+ T lymphocytes genetically modified with VRX496 (VRX496T) into HIV-infected patients is intended to provide a reservoir of cells capable of controlling HIV, potentially delaying AIDS onset," wrote L.M. Humeau and colleagues.

"To determine the patient population likely to respond to VRX496 for optimal efficacy," said investigators, "we examined the ability of our research vector, VRX494, to modify and suppress HIV in vitro in lymphocytes isolated from 20 study subjects discordant for CD4 count and viral load.

"VRX494 is analogous to the clinical vector VRX496, except that it contains GFP as a marker gene instead of the 186-tag marker in the clinical vector."

Humeau continued, "To transfer VRX494 to target cells we developed a novel scalable two-step transduction procedure that has been translated to the clinic in an ongoing clinical trial. This procedure achieved unprecedented transduction efficiencies of 94±5% in HIV+ study subject cells.

"In addition, the vector inhibited HIV replication, greater than or equal to93% in culture regardless of the viral load or CD4 count of the subject or tropism of the virus strain with which they were infected."

"These findings demonstrate that VRX496T therapy is expected to be beneficial to patients that differ in their status in term of CD4 count and viral load.

"The methods described represent significant technical advances facilitating execution of lentivirus vector-mediated gene therapy for treatment of HIV and are currently being employed in the first trial evaluating lentivirus vector safety in humans," the authors concluded.

Humeau and colleagues published their study in Molecular Therapy (Efficient lentiviral vector-mediated control of HIV-1 replication in CD4 lymphocytes from diverse HIV+ infected patients grouped according to CD4 count and viral load. Mol Ther. 2004 Jun;9(6):902-13.

For additional information, contact B. Dropulic, VIRxSYS Corp., 200 Perry Pkwy, Ste. 1A, Gaithersburg, MD 20877 USA.

The publisher's contact information for the journal Molecular Therapy is: Academic Press Inc. Elsevier Science, 525 B St., Ste. 1900, San Diego, CA 92101-4495 USA.

The information in this article comes under the major subject areas of Biotechnology, Gene Therapy, HIV/AIDS, and Molecular Virology.

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

Reference

Humeau LM, Binder GK, Lu X, et al., "Efficient lentiviral vector-mediated control of HIV-1 replication in CD4 lymphocytes from diverse HIV+ infected patients grouped according to CD4 count and viral load", Mol Ther. 2004 Jun;9(6):902-13.

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