Gene Therapeutic Approaches for Immune Modulation in AIDS

Antiviral drug therapy can effectively suppress HIV replication, but emerging viral resistance and drug toxicity limit long-term therapeutic efficacy. In addition, regeneration of the T helper cell repertoire is often incomplete. The current major challenges in the treatment of HIV infection are therefore the reconstitution of cellular immunity, and especially of the HIV-specific immune response, and the suppression of virus replication in patients with HAART failure. Several gene therapeutic strategies for immune reconstitution of AIDS patients have been described. Preclinical and clinical studies have examined the safety and efficacy of two basic approaches: firstly, the transfer of autologous T cells armed with recombinant receptors that target HIV antigens to specifically increase antiviral immunity and, secondly, the transfer of genetically modified T cells or hematopoietic progenitor cells that express an antiviral gene. However, for both approaches, engraftment levels of gene-modified cells have not been sufficient to reconstitute cellular immunity and to effectively reduce the overall viral load in patients. Strategies to improve the technologies and procedures involved in gene therapeutic immune reconstitution of AIDS patients are discussed.