| 摘要 |
Human immunodeficiency virus (HIV) is the primary etiologic agent for the acquired immune deficiency syndrome (AIDS). HIV exhibits considerable genotypic and phenotypic variability as manifested by different replicative kinetics, susceptibility to serum neutralization, antiviral drug resistance, cytopathic effects, and host-cell range specificity. Infection by HIV leads to progressive deterioration of cell-mediated immune responses making infected patients susceptible to a variety of opportunistic infections, such as pneumocystis carinii pneumonia (PCP), as well as, to the development of tumors such as Kaposi's sarcoma (KS). While the use of live-attenuated viruses to treat HIV infection has been proposed, to date researchers have been unable to demonstrate their efficacy in a clinical setting. The claimed invention addresses this defect by providing therapeutic compositions and methods of treatment employing viral suspensions prepared from cells transfected with a recombinant HIV-1 nef-deficient molecular clone. The HIV-1 nef gene product is required for efficient viral replication and pathogenicity in vivo. Nef may exert its effects through the downregulation of CD4 by endocytosis and lysosomal degradation, although other activities have also been ascribed to this gene product. Accordingly, this gene product was targeted for inactivation and a recombinant HIV-1ELI molecular clone was generated containing an NcoI/XhoI nef deletion. Suspensions comprising viral particles generated from cells transfected with the recombinant clone were prepared and administered to HIV-infected patients. Patients receiving these suspensions displayed a statistically significant reduction in viral burden and increase in CD4<+> lymphocyte counts during the study. The claimed compositions should facilitate the reduction of viral burden and the restoration of CD4<+> lymphocyte levels in HIV-1-infected subjects.
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