1 Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 CHIP, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet4 unknown5 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet6 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
BACKGROUND: ESPRIT is a randomized trial comparing the clinical impact of interleukin (IL)-2 plus antiretrovirals vs antiretrovirals alone. Identification of factors that influence the relationship between IL-2 and CD4 count recovery will enable better personalization of treatment with IL-2 in HIV-1-positive individuals. The IL-2 induction phase consists of three dosing cycles over 6-8 months (7.5 MIU twice a day, for 5 days every 8 weeks). METHODS: We included patients initiating IL-2 at the 7.5 MIU dose with an 8-month CD4 count, measured at least 30 days after their last cycle. We identified baseline predictors of CD4 count changes over 8 months using linear regression. RESULTS: Of 2090 patients assigned IL-2, 1673 (80%) were included in the analysis. The median (interquartile range) baseline CD4 count was 461 (370, 587) cells/microL with a median increase of 233 (90, 411) cells/microL at month 8. After adjustments, significant predictors of CD4 count change included CD4 nadir (29.8 cells/microL greater increase per 100 cells/microL higher; P<0.0001), last CD4 count before baseline (mean 36.0 cells/microL greater increase per 100 cells/microL higher; P<0.0001), time from antiretroviral start to baseline (8.3 cells/microL smaller increase per year longer; P=0.001), age (11.7 cells/microL smaller increase per 5 years older; P=0.005) and race (79.7 cells/microL greater increase for black patients vs white patients; P=0.003). A linear relationship existed between total IL-2 dose in the first cycle and CD4 count change (73.1 cells/microL greater increase per 15 MIU higher; P<0.0001). CONCLUSIONS: Prior nadir and current CD4 counts, age and IL-2 dose are major determinants of CD4 increases induced by with intermittent administration of IL-2 in HIV-1-positive individuals on antiretrovirals. The clinical function of these induced CD4 cells is under study.
Hiv Medicine, 2007, Vol 8, Issue 2, p. 112-23
Adult; CD4 Lymphocyte Count; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Interleukin-2; Male; Patient Compliance; RNA, Viral; Recombinant Proteins; Reverse Transcriptase Inhibitors; Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial