Progress towards gene therapy for HIV infection.

The retroviral life cycle and genetic plasticity of human immunodeficiency virus 1 (HIV-1) present unprecedented therapeutic challenges. Twelve years into the HIV epidemic, satisfactory treatment remains elusive. Our current understanding of AIDS pathogenesis calls for early intervention with antiviral agents. Although still in its infancy, human gene therapy holds considerable potential for the long-term treatment of genetic disorders, cancer and chronic infectious diseases. Gene therapy for HIV infection is receiving particularly intensive study: approaches that are in development include both immunotherapy (e.g. therapeutic vaccines and adoptive transfer of CD8+ T-cell clones) and direct antiviral therapy (intracellular immunization). The latter strategies include transdominant modifications of HIV proteins, RNA decoys, antisense RNA, ribozymes and modifications of cellular proteins (e.g. intracellular antibodies, soluble CD4). Several of these strategies are now entering clinical trials. While significant conceptual and technical hurdles remain to be overcome before the promise of gene therapy for HIV infection can be fully realized, progress in this field is likely to be rapid and to contribute to the broader applicability of human gene therapy to the treatment of other disorders.