A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy.

Abstract Highly active antiretroviral therapy (HAART) can suppress HIV replication to undetectable levels in plasma, but it is unlikely to eradicate cellular reservoirs of virus. Immunotherapies that are cytolytic may be useful adjuncts to drug therapies that target HIV replication. We have generated HIV-specific CD4 + and CD8 + T cells bearing a chimeric T-cell receptor (CD4ζ) composed of the extracellular and transmembrane domain of human CD4 (which binds HIVgp120) linked to the intracellular-ζ signaling chain of the CD3 T-cell receptor. CD4ζ-modified T cells can inhibit viral replication, kill HIV-infected cells in vitro , and survive for prolonged periods in vivo . We report the results of a phase II randomized trial of CD4ζ gene–modified versus unmodified T cells in 40 HIV-infected subjects on HAART with plasma viral loads + T-cell counts.