BACKGROUND: In advance of a large clinical end point trial evaluating the effectiveness of subcutaneous interleukin 2 (scIL-2) for treatment of patients with human immunodeficiency virus (HIV) infection, 3 identically designed Vanguard trials were conducted in Buenos Aires, Argentina; Bangkok, Thailand; and Houston, Texas. To more precisely quantitate the effect on CD4 cell response of 3 different doses of scIL-2 that were administered twice daily for 5 days every 8 weeks, the results of these 3 trials were pooled in a meta-analysis. METHODS: Two hundred eighteen HIV-1-infected subjects who were receiving antiretroviral therapy and who had a baseline CD4 cell count of > or =350 cells/mm3 were consecutively randomized to receive scIL-2 at a dose of 1.5 mIU (n=36) or a control regimen (n=36); or scIL-2 at a dose of 4.5 mIU (n=36) or a control regimen (n=36); or scIL-2 at a dose of 7.5 mIU (n=37) or a control regimen (n=37). After completion of 3 cycles of therapy, the subjects were enrolled in an extension phase (months 6-12). Subjects were encouraged to receive additional cycles of scIL-2 to maintain a CD4 cell count of more than twice the baseline count or >1000 cells/mm3. RESULTS: After completion of 3 cycles of scIL-2, the mean CD4 cell count changes from baseline (calculated as changes from baseline in a scIL-2 group minus changes from baseline in its contemporaneous control group) were 67 (P=.14), 339 (P<.0001), and 605 cells/mm3 (P<.0001) for the 1.5, 4.5, and 7.5 mIU dose groups, respectively (P<.0001 for differences among dose groups). Between months 6 and 12, a total of 78%, 39%, and 32% of subjects assigned to the 1.5, 4.5, and 7.5 mIU dose groups, respectively, needed at least 1 additional cycle to achieve the CD4 cell count goal. At 12 months, the differences in the mean change in CD4 cell count from baseline between each scIL-2 dose group and its contemporaneous control group were 184, 369, and 432 cells/mm3, respectively (P=.01 for differences among dose groups). CONCLUSIONS: Although CD4 cell count increases were seen in all 3 dose groups, higher scIL-2 doses resulted in greater CD4 cell count changes after 6 months, compared with control groups.
BACKGROUND: In advance of a large clinical end point trial evaluating the effectiveness of subcutaneous interleukin 2 (scIL-2) for treatment of patients with human immunodeficiency virus (HIV) infection, 3 identically designed Vanguard trials were conducted in Buenos Aires, Argentina; Bangkok, Thailand; and Houston, Texas. To more precisely quantitate the effect on CD4 cell response of 3 different doses of scIL-2 that were administered twice daily for 5 days every 8 weeks, the results of these 3 trials were pooled in a meta-analysis. METHODS: Two hundred eighteen HIV-1-infected subjects who were receiving antiretroviral therapy and who had a baseline CD4 cell count of > or =350 cells/mm3 were consecutively randomized to receive scIL-2 at a dose of 1.5 mIU (n=36) or a control regimen (n=36); or scIL-2 at a dose of 4.5 mIU (n=36) or a control regimen (n=36); or scIL-2 at a dose of 7.5 mIU (n=37) or a control regimen (n=37). After completion of 3 cycles of therapy, the subjects were enrolled in an extension phase (months 6-12). Subjects were encouraged to receive additional cycles of scIL-2 to maintain a CD4 cell count of more than twice the baseline count or >1000 cells/mm3. RESULTS: After completion of 3 cycles of scIL-2, the mean CD4 cell count changes from baseline (calculated as changes from baseline in a scIL-2 group minus changes from baseline in its contemporaneous control group) were 67 (P=.14), 339 (P<.0001), and 605 cells/mm3 (P<.0001) for the 1.5, 4.5, and 7.5 mIU dose groups, respectively (P<.0001 for differences among dose groups). Between months 6 and 12, a total of 78%, 39%, and 32% of subjects assigned to the 1.5, 4.5, and 7.5 mIU dose groups, respectively, needed at least 1 additional cycle to achieve the CD4 cell count goal. At 12 months, the differences in the mean change in CD4 cell count from baseline between each scIL-2 dose group and its contemporaneous control group were 184, 369, and 432 cells/mm3, respectively (P=.01 for differences among dose groups). CONCLUSIONS: Although CD4 cell count increases were seen in all 3 dose groups, higher scIL-2 doses resulted in greater CD4 cell count changes after 6 months, compared with control groups.
Authors: V H Barbai; E Ujhelyi; J Szlávik; I Vietorisz; L Varga; E Fey; G Füst; D Bánhegyi Journal: Clin Exp Immunol Date: 2010-04-09 Impact factor: 4.330
Authors: Brian O Porter; Jean Shen; Joseph A Kovacs; Richard T Davey; Catherine Rehm; Jay Lozier; Gyorgy Csako; Khanh Nghiem; Rene Costello; Henry Clifford Lane; Irini Sereti Journal: AIDS Date: 2009-09-24 Impact factor: 4.177
Authors: Brian O Porter; Kara B Anthony; Jean Shen; Barbara Hahn; Chris E Keh; Frank Maldarelli; William C Blackwelder; Henry Clifford Lane; Joseph A Kovacs; Richard T Davey; Irini Sereti Journal: AIDS Date: 2009-01-14 Impact factor: 4.177
Authors: D Abrams; Y Lévy; M H Losso; A Babiker; G Collins; D A Cooper; J Darbyshire; S Emery; L Fox; F Gordin; H C Lane; J D Lundgren; R Mitsuyasu; J D Neaton; A Phillips; J P Routy; G Tambussi; D Wentworth Journal: N Engl J Med Date: 2009-10-15 Impact factor: 91.245
Authors: Philip Bejon; Sheila Keating; Jedidah Mwacharo; Oscar K Kai; Susanna Dunachie; Michael Walther; Tamara Berthoud; Trudie Lang; Judy Epstein; Daniel Carucci; Philippe Moris; Joe Cohen; Sarah C Gilbert; Norbert Peshu; Kevin Marsh; Adrian V S Hill Journal: Infect Immun Date: 2006-09-11 Impact factor: 3.441