SAFETY AND ANTIVIRAL EFFICACY OF IMMUNOTHERAPY WITH AUTOLOGOUS CD8+ HIV-SPECIFIC

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Highly active antiretroviral therapy (HAART) can suppress HIV replication to undetectable levels. However, even after years of uninterrupted therapy and as soon as HAART is stopped, viral replication is rapidly reinitiated and progression to disease occurs. Viral persistence in individuals on HAART is due, in part, to the long-term survival of a pool of infected, resting CD4+ T cells and to low levels of ongoing HIV replication despite HAART suppression. This viral turnover could account for the constant replenishment of the HIV reservoir under HAART. Further studies have shown that gut and lymphoid tissues are major sites for such reservoirs. This phase I/II clinical study proposes to target sites of ongoing HIV replication in patients on HAART by the adoptive transfer of large amounts of HIV-specific CD8+ T cells. The safety and efficacy of transferred CD8+ T cells on HIV+ replication in patients with low viral burdens, most likely receiving HAART, will be evaluated. It will be determined if the administration of a 14 day course of low-dose s.c. IL-2 can promote the persistence and antiviral activity of transferred cells, as shown in adoptive transfer studies of melanoma-specific CD8+ T cell clones. The localization of HIV-specific CD8+ T cells to known sites of residual viral replication will be compared to the concomitant infusion of a CMV-specific clone used as a control. We plan to administer 3.3 x 109/m2 cells of an HIV and a CMV clone to 10 patients with a 1 month interval, the second infusion followed by 14 days of s.c. IL-2.