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.
Bibliographical noteFunding Information:
Financial support. The National Centre in HIV Epidemiology and Clinical Research (NCHECR) at the University of New South Wales, Sydney, Australia, is funded by the Commonwealth Department of Health and Aging (Australia). This study was partially supported by Intramural Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.