Safety, tolerability, pharmacokinetics, and efficacy of an interleukin-2 agonist among HIV-infected patients receiving highly active antiretroviral therapy

Journal of Interferon and Cytokine Research

Volumn 28, Issue 2, 2008, Pages 89-100

  Davey, Richard T ^a   Pertel, Peter E ^b   Benson, Alice ^b   Cassell, Delanie J ^b   Gazzard, Brian G ^c   Holodniy, Mark ^d,m   Lalezari, Jacob P ^e   Levy, Yves ^f   Mitsuyasu, Ronald T ^g   Palella, Frank J ^h   Pollard, Richard B ⁱ   Rajagopalan, Prabhu ^b   Saag, Michael S ^j   Salata, Robert A ^k   Sha, Beverly E ^l   Choudhri, Shurjeel ^b  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b BAYER CORPORATION   (United States)

^c CHELSEA AND WESTMINSTER HOSPITAL   (United Kingdom)

^d VA PALO ALTO HEALTH CARE SYSTEM   (United States)

^e Quest Clinical Research   (United States)

^f HENRI MONDOR HOSPITAL   (France)

^g UCLA MEDICAL CENTER   (United States)

^h NORTHWESTERN UNIVERSITY   (United States)

ⁱ UNIVERSITY OF CALIFORNIA   (United States)

^j UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^k UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

^l RUSH UNIVERSITY MEDICAL CENTER   (United States)

^m STANFORD UNIVERSITY   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BAY 50 4798; CYTOKINE RECEPTOR AGONIST; PLACEBO; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; CD4 LYMPHOCYTE COUNT; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DRY SKIN; EXFOLIATIVE DERMATITIS; FEMALE; FEVER; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERTRIGLYCERIDEMIA; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; NEUTROPENIA; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PRURITUS; RASH; RHINITIS;

ADULT; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CYTOKINES; DOUBLE-BLIND METHOD; FEMALE; HIV INFECTIONS; HUMANS; INJECTIONS, SUBCUTANEOUS; INTERLEUKIN-2; LYMPHOCYTE COUNT; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; RECOMBINANT PROTEINS;

EID: 39449086420     PISSN: 10799907     EISSN: None     Source Type: Journal    
DOI: 10.1089/jir.2007.0064     Document Type: Article

References (27)

1. Caligiuri MA, Murray C, Soiffer RJ, Klumpp TR, Seiden M, Cochran K, Cameron C, Ish C, Buchanan L, Perillo D. 1991. Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer: prolonged immunomodulation without significant toxicity. J Clin Oncol 9:2110-2119.
2. Carr A, Emery S, Lloyd A, Hoy J, Garsia R, French M, Stewart G, Fyfe G, Cooper DA. 1998. Outpatient continuous intravenous interleukin-2 or subcutaneous, polyethylene glycol-modified interleukin-2 in human immunodeficiency virus-infected patients: a randomized, controlled, multicenter study. Australian IL-2 Study Group. J Infect Dis 178:992-999.
3. Cassell DJ, Choudhri S, Humphrey R, Martell RE, Reynolds T, Shanafelt AB. 2002. Therapeutic enhancement of IL-2 through molecular design. Curr Pharm Des 8: 2171-2183.
4. Davey RT Jr, Chaitt DG, Piscitelli SC, Wells M, Kovacs JA, Walker RE, Falloon J, Polis MA, Metcalf JA, Masur H, Fyfe G, Lane HC. 1997. Subcutaneous administration of interleukin-2 in human immunodeficiency virus type 1-infected persons. J Infect Dis 175: 781-789.
5. Davey RT Jr, Murphy RL, Graziano FM, Boswell SL, Pavia AT, Cancio M, Nadler JP, Chaitt DG, Dewar RL, Sahner DK, Duliege AM, Capra WB, Leong WP, Giedlin MA, Lane HC, Kahn JO. 2000. Immunologic and virologic effects of subcutaneous interleukin 2 in combination with antiretroviral therapy: A randomized controlled trial. JAMA 284:183-189.
6. + T cells. Clin Immunol 106:188-196.
7. Jacobson EL, Pilaro F, Smith KA. 1996. Rational interleukin 2 therapy for HIV positive individuals: daily low doses enhance immune function without toxicity. Proc Natl Acad Sci USA 93:10405-10410.
8. + T lymphocytes by intermittent IL-2 therapy in HIV-infected patients. J Clin Invest 115:2139-48.
9. Kovacs JA, Vogel S, Albert JM, Falloon J, Davey RT Jr, Walker RE, Polis MA, Spooner K, Metcalf JA, Baseler M, Fyfe G, Lane HC. 1996. Controlled trial of interleukin-2 infusions in patients infected with the human immunodeficiency virus. N Engl J Med 335:1350-1356.
10. Kovacs JA, Vogel S, Metcalf JA, Baseler M, Stevens R, Adelsberger J, Lempicki R, Hengel RL, Sereti I, Lambert L, Dewar RL, Davey RT Jr, Walker RE, Falloon J, Polis MA, Masur H, Lane HC. 2001. Interleukin-2 induced immune effects in human immunodeficiency virus-infected patients receiving intermittent interleukin-2 immunotherapy. Eur J Immunol 31:1351-1360.
11. Lalezari JP, Beal JA, Ruane PJ, Cohen CJ, Jacobson EL, Sundin D, Leong WP, Raffanti SP, Wheeler DA, Anderson RD, Keiser P, Schrader SR, Goodgame JC, Steinhart CR, Murphy RL, Wolin MJ, Smith KA. 2000. Low-dose daily subcutaneous interleukin-2 in combination with highly active antiretroviral therapy in HIV+ patients: a randomized controlled trial. HIV Clin Trials 1:1-15.
12. Levy Y, Capitant C, Houhou S, Carriere I, Viard JP, Goujard C, Gastaut JA, Oksenhendler E, Boumsell L, Gomard E, Rabian C, Weiss L, Guillet JG, Delfraissy JF, Aboulker JP, Seligmann M; ANRS 048 study group. 1999. Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial. Lancet 353:1923-1929.
13. Levy Y, Durier C, Krzysiek R, Rabian C, Capitant C, Lascaux AS, Michon C, Oksenhendler E, Weiss L, Gastaut JA, Goujard C, Rouzioux C, Maral J, Delfraissy JF, Emilie D, Aboulker JP; ANRS 079 Study Group. 2003. Effects of interleukin-2 therapy combined with highly active antiretroviral therapy on immune restoration in HIV-1 infection: a randomized controlled trial. AIDS 17:343-351.
14. Liegler TJ, Stites DP. 1994. HIV-1 gp120 and anti-gp120 induce reversible unresponsiveness in peripheral CD4 T lymphocytes. J Acquir Immune Defic Syndr 7:340-348.
15. Matthews L, Chapman S, Ramchandani MS, Lane HC, Davey RT Jr, Sereti I. 2004. BAY 50-4798, a novel, high-affinity receptor-specific recombinant interleukin-2 analog, induces dose-dependent increases in CD25 expression and proliferation among unstimulated, human peripheral blood mononuclear cells in vitro. Clin Immunol 113:248-245.
16. (+) T-lymphocyte expansion. Clin Immunol 99:30-42.
17. Mitsuyasu R, Gelman R, Cherng DW, Landay A, Fahey J, Reichman R, Erice A, Bucy RP, Kilby JM, Lederman MM, Hamilton CD, Lertora J, White BL, Tebas P, Duliege AM, Pollard RB; AIDS Clinical Trials Group 328 Study Team. 2007. The virologic, immunologic, and clinical effects of interleukin 2 with potent antiretroviral therapy in patients with moderately advanced human immunodeficiency virus infection: a randomized controlled clinical trial. Arch Intern Med 167:597-605.
18. Peest D, Leo R, Bloche S, Hein R, Stannat-Kiessling S, Tschechne B, Fett W, Harms P, Hoffmann L, Bartl R, et al. 1995. Low-dose recombinant interleukin-2 therapy in advanced multiple myeloma. Br J Haematol 89:328-337.
19. Piscitelli SC, Forrest A, Vogel S, Chaitt D, Metcalf J, Stevens R, Baseler M, Davey RT, Kovacs JA. 1998. Pharmacokinetic modeling of recombinant interleukin-2 in patients with human immunodeficiency virus infection. Clin Pharmacol Ther 64:492-498.
20. Ruxrungtham K, Suwanagool S, Tavel JA, Chuenyam M, Kroon E, Ubolyam S, Buranapraditkun S, Techasathit W, Li Y, Emery S, Davey RT, Fosdick L, Kunanusont C, Lane HC, Phanuphak P; Vanguard Study Group. 2000. A randomized, controlled 24-week study of intermittent subcutaneous interleukin-2 in HIV-1 infected patients in Thailand. AIDS 14:2509-2513.
21. Shanafelt AB, Lin Y, Shanafelt MC, Forte CP, Dubois-Stringfellow N, Carter C, Gibbons JA, Cheng SI, Delaria KA, Fleischer R, Greve JM, Gundel R, Harris K, Kelly R, Koh B, Li Y, Lantz L, Mak P, Neyer L, Plym MJ, Roczniak S, Serban D, Thrift J, Tsuchiyama L, Wetzel M, Wong M, Zolotorev A. 2000. A T cell-selective interleukin 2 mutein exhibits potent antitumor activity and is well tolerated in vivo. Nat Biotechnol 18:1197-1201
22. Shearer GM, Bernstein DC, Tung KS, Via CS, Redfield R, Salahuddin SZ, Gallo RC. 1986. A model for the selective loss of major histocompatibility complex self-restricted T cell immune responses during the development of acquired immune deficiency (AIDS). J Immunol 137:2514-2521.
23. Siegel JP, Sharon M, Smith PL, Leonard WJ. 1987. The IL-2 receptor β chain (p70): role in mediating signals for LAK, NK, and proliferative activities. Science 238:75-78.
24. Stein RC, Malkovska V, Morgan S, Galazka A, Aniszewski C, Roy SE, Shearer RJ, Marsden RA, Bevan D, Gordon-Smith EC, et al. 1991. The clinical effects of prolonged treatment of patients with advanced cancer with low-dose subcutaneous interleukin-2. Br J Cancer 63:275-278 (erratum pubished in Br J Cancer 1991;63:1029).
25. Steppan S, Eckart MR, Bajsarowicz K, Sternberg LR, Greve JM, Cassell DJ. 2006. Reduced secondary cytokine induction by BAY 50-4798, a high-affinity receptor-specific interleukin-2 analog. J Interferon Cytokine Res 26:171-178.
26. Voss SD, Sondel PM, Robb RJ. 1992. Characterization of the interleukin 2 receptors (IL-2R) expressed on human natural killer cells activated in vivo by IL-2: association of the p64 IL-2R γ chain with the IL-2R β chain in functional intermediate-affinity IL-2R. J Exp Med 176:531-541.
27. Witzke O, Winterhagen T, Reinhardt W, Heemann U, Grosse-Wilde H, Kreuzfelder E, Roggendorf M, Philipp T. 1998. Comparison between subcutaneous and intravenous interleukin-2 treatment in HIV disease. J Intern Med 244:235-240.