@article{8ce88ed9e14d470aae2b7efe531caf57,
title = "Interleukin-2 therapy in patients with HIV infection",
abstract = "BACKGROUND: Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known. METHODS: We conducted two trials: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either 50 to 299 per cubic millimeter (SILCAAT) or 300 or more per cubic millimeter (ESPRIT) were randomly assigned to receive interleukin-2 plus antiretroviral therapy or antiretroviral therapy alone. The interleukin-2 regimen consisted of cycles of 5 consecutive days each, administered at 8-week intervals. The SILCAAT study involved six cycles and a dose of 4.5 million IU of interleukin-2 twice daily; ESPRIT involved three cycles and a dose of 7.5 million IU twice daily. Additional cycles were recommended to maintain the CD4+ cell count above predefined target levels. The primary end point of both studies was opportunistic disease or death from any cause. RESULTS: In the SILCAAT study, 1695 patients (849 receiving interleukin-2 plus antiretroviral therapy and 846 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 202 cells per cubic millimeter were enrolled; in ESPRIT, 4111 patients (2071 receiving interleukin-2 plus antiretroviral therapy and 2040 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 457 cells per cubic millimeter were enrolled. Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone--by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. Hazard ratios for opportunistic disease or death from any cause with interleukin-2 plus antiretroviral therapy (vs. antiretroviral therapy alone) were 0.91 (95\% confidence interval [CI], 0.70 to 1.18; P=0.47) in the SILCAAT study and 0.94 (95\% CI, 0.75 to 1.16; P=0.55) in ESPRIT. The hazard ratios for death from any cause and for grade 4 clinical events were 1.06 (P=0.73) and 1.10 (P=0.35), respectively, in the SILCAAT study and 0.90 (P=0.42) and 1.23 (P=0.003), respectively, in ESPRIT. CONCLUSIONS: Despite a substantial and sustained increase in the CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit in either study. (ClinicalTrials.gov numbers, NCT00004978 [ESPRIT] and NCT00013611 [SILCAAT study].)",
keywords = "AIDS-Related Opportunistic Infections, Adult, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Therapy, Combination, Female, Follow-Up Studies, HIV, HIV Infections, Humans, Injections, Subcutaneous, Interleukin-2, Male, RNA, Viral, Recombinant Proteins",
author = "NN NN and NN NN and D Abrams and Y L{\'e}vy and Losso, \{M H\} and A Babiker and G Collins and Cooper, \{D A\} and J Darbyshire and S Emery and L Fox and F Gordin and Lane, \{H C\} and Lundgren, \{J D\} and R Mitsuyasu and Neaton, \{J D\} and A Phillips and Routy, \{J P\} and G Tambussi and D Wentworth",
note = "2009 Massachusetts Medical Society",
year = "2009",
doi = "10.1056/NEJMoa0903175",
language = "English",
volume = "361",
pages = "1548--59",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "16",
}