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Safety of Autologous, Ex Vivo-Expanded Human Immunodeficiency Virus (HIV)-Specific Cytotoxic T-Lymphocyte Infusion in HIV-Infected Patients
Judy Lieberman,
Paul R. Skolnik,
G. Robert Parkerson III,
Jessica A. Fabry,
Bernard Landry,
James Bethel,
Jonathan Kagan, and
the DATRI 006 Study Team
From the Center for Blood Research, Harvard Medical School, Boston, MA; the Division of Hematology-Oncology, and Geographic Medicine and Infectious Diseases, Department of Medicine, New England Medical Center, Boston, MA; Westat, Rockville, MD; and the Division of AIDS, National Institute for Allergy and Infectious Diseases, Rockville, MD.
We infused six human immunodeficiency virus (HIV)-seropositive subjects with autologous CD8+ cytotoxic T cells (CTLs) enriched for HIV-specific cytotoxicity targeted against a diversity of HIV epitopes in gp120, gag p17 and p24, and nef. There was no toxicity and no subject deteriorated clinically. In the first 2 weeks, CD4 counts increased for all subjects and plasma viremia decreased in five of six subjects. Twenty-four weeks later, the mean values of all measures of viral burden and surrogate markers of HIV infection were either unchanged or improved, but none of the changes was statistically significant. Two subjects continued to have decreased cell-associated viral burden and another subject had more than doubled CD4 cell count. HIV-specific CTL activity increased in most subjects. The increase in CD4 T-cell counts in the first weeks after the infusion suggests that antiviral CTLs of diverse specificities do not play a significant role in CD4 T-cell decline. The lack of any acute toxicity or adverse effect on viral burden suggests that therapy with antiviral CTLs deserves further study.
Blood, Vol. 90 No. 6 (September 15), 1997:
pp. 2196-2206
© 1997 by The American Society of Hematology.
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