A5214: SQ SINGLE DOSE INTERLEUKIN-7 IN HIV-1 INFECTED SUBJECTS

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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. This is a phase I, randomized, placebo-controlled, double-blind sequential cohort dose-escalation study of single dose subcutaneous injection of rhIL-7 in HIV-1 infected subjects receiving potent ART with CD4+ counts > 100 cells/mm3 and viral load > 50,000 copies/ml. The study will look at the safety of biologically active doses of IL-7 and will study the biologic effect of rhIL-7 (CD127, alpha chain of the IL-7 receptor) on CD4 and CD8 T-cells, expression of intracellular bcI-2 in T-cells and development of IL-7 antibodies. It will also study the pharmacokinetic profile of rhIL-7 in HIV-1 infected subjects. Doses will be escalated from 3-100ug/kg. For each dose (3, 10, 30, 60 and 100ug/kg) of active rhIL-7 drug or placebo, subjects will be stratified at entry (viral load < 50 copies/mL or viral load 50-50,000 copies/mL). Within each stratum, subjects will be randomized 3:1 (exactly three subjects in each arm receiving rhIL-7 and exactly one subject in the arm receiving placebo). The primary endpoint is safety: for each stratum, the maximum toxic dosage (MTD) of rhIL-7 will be reported. For each stratum and dose, the frequency of dose-limiting toxicity (DLT) will be described by treatment arm and specific AEs and/or laboratory evaluations that constituted the DLT. Secondary endpoints include CD8/CD127 ratio and pharmacokinetics. Of 40-50 subjects nationally, 2-3 subjects will be recruited at MHMC. There will be a pre-screening, a screening and a 12-hour PK entry visit. Post entry, patients will be seen about seven times during eight weeks of follow-up.