A Phase II Study of Intermittent Recombinant Human Interleukin-2 (rhIL-2) by Intravenous or Subcutaneous Administration in Subjects With HIV Infection on Highly Active Antiretroviral Therapy (HAART) Compared to HAART Alone

Summary

To compare two different routes of intermittently administered rhIL-2 with a highly active antiretroviral regimen (HAART) to HAART alone. The comparison is based on the following: proportion of patients achieving at least 50-percent increase in CD4 counts above prerandomization baseline values after 1 year of rhIL-2 and the rate of change in CD4 counts. To compare the safety and tolerance of these regimens and their effect on quality of life. To assess the effects of rhIL-2 when combined with HAART on changes in immune cell phenotypes and function and on HIV viral load and the rate of antiviral drug resistance development. The poor responsiveness of late stage HIV-infected patients to rhIL-2 is thought to occur because of low T cell regenerative capacity and high viral burden. If means were available to effectively suppress virus replication, the indigenous immune restorative responses of the host may be further stimulated and enhanced by rhIL-2. The use of protease inhibitors with nucleoside-analogue combination regimens appears to be most effective in controlling virus replication. High-dose intermittent rhIL-2 administered either intravenously or subcutaneously has been shown to be effective in inducing CD4 responses in a number of studies.

Timeline

Start

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Primary completion

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Completion

2007-03

Publications

• Background Reier A, Mitsuyasu RT. Use of interleukin-2 in immunotherapy of human immunodeficiency virus infection. BioDrugs. 1998 Sep;10(3):215-25. doi: 10.2165/00063030-199810030-00005.
• Background Bucy RP, Hockett RD, Derdeyn CA, Saag MS, Squires K, Sillers M, Mitsuyasu RT, Kilby JM. Initial increase in blood CD4(+) lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues. J Clin Invest. 1999 May 15;103(10):1391-8. doi: 10.1172/JCI5863.
• Background Mitsuyasu R, Pollard R, Gelman R, Weng D. Prospective, randomized, controlled phase II study of highly active antiretroviral therapy (HAART) with continuous IV (CIV) or subcutaneous (SC) interleukin-2 (IL-2) in HIV-infected patients with CD4+counts of 50-350 cells/mm3: ACTG 328-final results at 84 weeks. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 17)
• Background Hockett RD, Kilby JM, Derdeyn CA, Saag MS, Sillers M, Squires K, Chiz S, Nowak MA, Shaw GM, Bucy RP. Constant mean viral copy number per infected cell in tissues regardless of high, low, or undetectable plasma HIV RNA. J Exp Med. 1999 May 17;189(10):1545-54. doi: 10.1084/jem.189.10.1545.

Drugs

Indications