Repeated Cycles of Recombinant Human Interleukin 7 in HIV-Infected Patients With Low CD4 T-Cell Reconstitution on Antiretroviral Therapy: Results of 2 Phase II Multicenter Studies
CLINICAL INFECTIOUS DISEASES(2016)
摘要
Background. Phase I/II studies in human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy have shown that a single cycle of 3 weekly subcutaneous (s/c) injections of recombinant human interleukin 7 (r-hIL-7) is safe and improves immune CD4 T-cell restoration. Herein, we report data from 2 phase II trials evaluating the effect of repeated cycles of r-hIL-7 (20 mu g/kg) with the objective of restoring a sustained CD4 T-cell count >500 cells/mu L. Methods. INSPIRE 2 was a single-arm trial conducted in the United States and Canada. INSPIRE 3 was a 2 arm trial with 3: 1 randomization to r-hIL-7 versus control conducted in Europe and South Africa. Participants with plasma HIV RNA levels <50 copies/mL during antiretroviral therapy and with CD4 T-cell counts between 101 and 400 cells/mu L were eligible. A repeat cycle was administered when CD4 T-cell counts fell to < 550 cells/mu L. Results. A total of 107 patients were treated and received 1 (n = 107), 2 (n = 74), 3 (n = 14), or 4 (n = 1) r-hIL-7 cycles during a median follow-up of 23 months. r-hIL-7 was well tolerated. Four grade 4 events were observed, including 1 case of asymptomatic alanine aminotransferase elevation. After the second cycle, anti-r-hIL-7 binding antibodies developed in 82% and 77% of patients in INSPIRE 2 and 3, respectively (neutralizing antibodies in 38% and 37%), without impact on the CD4 T-cell response. Half of the patients spent >63% of their follow-up time with a CD4 T-cell count > 500 cells/mu L. Conclusions. Repeated cycles of r-hIL-7 were well tolerated and achieved sustained CD4 T-cell restoration to > 500 cells/mu L in the majority of study participants.
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关键词
interleukin-7,HIV,immune restoration,T-cell recovery,CD4
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