Low-dose prolonged intermittent interleukin-2 adjuvant therapy: results of a randomized trial among human immunodeficiency virus-positive patients with advanced immune impairment.
Twenty-two patients with CD4(+)cell counts <or=200 cells/microL after 12 months of stable highly active antiretroviral therapy (HAART; "immunologic nonresponders") were randomly assigned to receive subcutaneous low-dose prolonged intermittent interleukin (IL)-2 in addition to HAART (n=12) or to continue HAART alone (n=10). At 48 weeks of follow-up, no IL-2-related serious adverse events and no significant differences in plasma human immunodeficiency virus (HIV) RNA level were observed in the 2 groups. A higher incidence of HIV-related clinical events was observed among patients receiving HAART alone (3/10) than among subjects receiving HAART plus IL-2 (0/12). Significant increases in CD4(+), naive, and CD4(+)CD7(+) cells and plasma levels of IL-7 were observed in patients receiving IL-2 versus patients receiving HAART alone. A significant increase in cell turnover did not lead to a decrease in the frequency of T cell receptor excision circles, which remained stable. Rather, increased numbers of T cell receptor excision circles per microliter of blood were observed (not statistically significant). Thus, adjuvant IL-2 therapy in immunologic nonresponders resulted in a clinical benefit, suggesting that the quantitative cell recovery involves functionally competent immune cells.
Marchetti
Giulia
G
Institute of Infectious Diseases and Tropical Medicine, Luigi Sacco Hospital, University of Milan, Milan, Italy. giulia.marchetti@unimi.it
Meroni
Luca
L
Varchetta
Stefania
S
Terzieva
Velislava
V
Bandera
Alessandra
A
Manganaro
Daniele
D
Molteni
Chiara
C
Trabattoni
Daria
D
Fossati
Sabrina
S
Clerici
Mario
M
Galli
Massimo
M
Moroni
Mauro
M
Franzetti
Fabio
F
Gori
Andrea
A
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006678:HIV / Q000254:growth & development* / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D015851:Interleukin-7 / Q000096:biosynthesis / Q000097:blood; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000097:blood; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D007376:Interleukin-2; D015851:Interleukin-7; D019394:Ki-67 Antigen; D011948:Receptors, Antigen, T-Cell