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 ≥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.