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.
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.
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: Sarah W Read; Richard A Lempicki; Michele Di Mascio; Sharat Srinivasula; Rosanne Burke; William Sachau; Marjorie Bosche; Joseph W Adelsberger; Irini Sereti; Richard T Davey; Jorge A Tavel; Chiung-Yu Huang; Haleem J Issaq; Stephen D Fox; H Clifford Lane; Joseph A Kovacs Journal: J Infect Dis Date: 2008-09-15 Impact factor: 5.226