Details

Autor(en) / Beteiligte

• Thiebaut, Rodolphe
• jarne, Ana
• Routy, Jean-Pierre
• Sereti, Irini
• Fischl, Margaret
• lve, Prudence
• Speck, Roberto F.
• D'Offizi, Gianpiero
• Casari, Salvatore
• Commenges, Daniel
• Foulkes, Sharne
• Natarajan, Ven
• Croughs, Therese
• Delfraissy, Jean-Francois
• Tambussi, Guiseppe
• Levy, Yves
• Lederman, Michael M.

Titel

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

Ist Teil von

• Clinical infectious diseases, 2016-05, Vol.62 (9), p.1178-1185

Ort / Verlag

United States: Oxford University Press

Erscheinungsjahr

2016

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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 μg/kg) with the objective of restoring a sustained CD4 T-cell count >500 cells/μL. 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/μL were eligible. A repeat cycle was administered when CD4 T-cell counts fell to <550 cells/μL. 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/μL. Conclusions. Repeated cycles of r-hIL-7 were well tolerated and achieved sustained CD4 T-cell restoration to >500 cells/μL in the majority of study participants. Clinical Trials Registration. INSPIRE II: clinicaltrials.gov (NCT01190111) and INSPIRE III: EudraCT (No. 2010-019773-15) and clinicaltrials.gov (NCT01241643).