Safety Study of IL-7 in HIV-infected Patients (Inspire)

Interleukin 7 (IL-7) is an essential cytokine for the thymic development and the post-thymic survival, expansion and maturation of T lymphocytes in humans. The rationale for using IL-7 as immunotherapy in HIV infection would be to support the expansion, survival and functional properties of T lymphocytes and enhance immune reconstitution. Phase I studies of a previous formulation of rhIL7 in cancer and HIV infected patients have shown that T cell proliferation and expansion can be achieved at doses that are well tolerated. The newly glycosylated form of IL-7 tested in this study has a longer half-life allowing weekly administrations. This is a phase I/IIa, open label, single arm trial that will test the safety of three subcutaneous injections of IL-7 at three different dose levels (10, 20 and 30 micrograms/kilograms) that will be tested sequentially. Eligible subjects (400 cells/microliters greater than CD4 greater than 101 cells/microliters and VL less than 1000 copies/milliliter, on antiretroviral therapy for at least one year) will be given 3 doses of IL-7 at weekly intervals (day 0, day 7 and day 14). Participants will be followed on days 0, 1, 4, 7, 14, 21 and 28 with additional visits on days 35, 56, and 77 and optional follow up every 3 months thereafter until week 56 (approximately 1 year after enrollment). The three doses will be tested sequentially (10, 20 and 30 micrograms/kilograms per dose) and dose escalation will occur only when safety data from day 28 of the previous dose level participants are complete. Ten subjects will enroll in each dose level and dose escalation will occur only after all subjects complete four weeks without evidence of dose-limiting toxicities. Secondary end points include a PK study of glycosylated rhIL7 as well as immunologic studies throughout the duration of the study to assess evidence of IL7 biologic activity with markers of T cell proliferation and expression of the alpha chain of the IL7 receptor. This is a multi-center international study sponsored by Cytheris with sites in USA, Canada, Italy and France. Children will be excluded and a separate study will be required in the future after the safety and biologic activity of this agent is established in adults. The study will enroll a total of approximately 30 participants.