Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: Results of a phase I/IIa randomized, placebo-controlled, multicenter study

Clinical Infectious Diseases

Volumn 55, Issue 2, 2012, Pages 291-300

  Levy Y ^a,b,c   Sereti, I ^d   Tambussi, G ^e   Routy, J P ^f   Lelievre J D ^a,c   Delfraissy, J F ^d   Molina, J M ^h   Fischl, M ⁱ   Goujard, C ^g   Rodriguez, B ⁿ   Rouzioux, C ^j   Avettand Fenoel V ^j   Croughs, T ^k   Beq, S ^k   Morre, M ^k   Poulin, J F ^l   Sekaly, R P ^l   Thiebaut, R ^m   Lederman, M M ⁿ  

^a INSERM U955   (France)

^b UNIVERSITÉ PARIS EST   (France)

^c HENRI MONDOR HOSPITAL   (France)

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

^e SAN RAFFAELE HOSPITAL   (Italy)

^f MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^g BICÊTRE HOSPITAL   (France)

^h SAINT LOUIS HOSPITAL   (France)

ⁱ UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^j ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

^k Cytheris SA   (France)

^l NIML   (Canada)

^m INSERM   (France)

ⁿ UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CYT 107; PROTEIN BCL 2; PROTEINASE INHIBITOR; RECOMBINANT INTERLEUKIN 7; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; T LYMPHOCYTE RECEPTOR; UNCLASSIFIED DRUG; VIRUS DNA;

ADULT; AGED; ARTICLE; CD4 LYMPHOCYTE COUNT; CLINICAL ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG TOLERABILITY; FEMALE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MALE; MEMORY T LYMPHOCYTE; MONITORING; MULTICENTER STUDY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL; REGULATORY T LYMPHOCYTE; SINGLE BLIND PROCEDURE; T LYMPHOCYTE; THYMUS; TOXICITY; VIREMIA;

ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CD4 LYMPHOCYTE COUNT; CD4-POSITIVE T-LYMPHOCYTES; HIV INFECTIONS; HUMANS; IMMUNOLOGIC FACTORS; INTERLEUKIN-7; PLACEBOS; RECOMBINANT PROTEINS; TREATMENT OUTCOME;

EID: 84864125153     PISSN: 10584838     EISSN: 15376591     Source Type: Journal    
DOI: 10.1093/cid/cis383     Document Type: Article

References (33)

1. von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med 1995; 181:1519-26.
2. Beq S, Delfraissy JF, Theze J. Interleukin-7 (IL-7): immune function, involvement in the pathogenesis of HIV infection and therapeutic potential. Euro Cytokine Netw 2004; 15:279-89. (Pubitemid 40127652)
3. Puel A, Ziegler SF, Buckley RH, Leonard WJ. Defective IL7R expression in T-B+NK+ severe combined immunodeficiency. Nat Gene 1998; 20:394-7. (Pubitemid 28541642)
4. Noguchi M, Nakamura Y, Russell SM, et al. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science 1993; 262:1877-80. (Pubitemid 24041859)
5. Bolotin E, Annett G, Parkman R, Weinberg K. Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count. Bone Marrow Transplant 1999; 23:783-8. (Pubitemid 29186888)
6. Napolitano LA, Grant RM, Deeks SG, et al. Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis. Nat Med 2001; 7:73-9. (Pubitemid 32095644)
7. Beq S, Nugeyre MT, Ho Tsong Fang R, et al. IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy. J Immunol 2006; 176:914-22. (Pubitemid 43099689)
8. Fry TJ, Moniuszko M, Creekmore S, et al. IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates. Blood 2003; 101:2294-9. (Pubitemid 36302072)
9. Mackall CL, Fry TJ, Bare C, Morgan P, Galbraith A, Gress RE. IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation. Blood 2001; 97: 1491-7. (Pubitemid 32183777)
10. Storek J, Gillespy T 3rd, Lu H, et al. Interleukin-7 improves CD4 T-cell reconstitution after autologous CD34 cell transplantation in monkeys. Blood 2003; 101:4209-18. (Pubitemid 36857906)
11. Beq S, Rozlan S, Gautier D, et al. Injection of glycosylated recombinant simian IL-7 provokes rapid and massive T-cell homing in rhesus macaques. Blood 2009; 114:816-25.
12. Levy Y, Lacabaratz C, Weiss L, et al. Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest 2009; 119:997-1007.
13. Rosenberg SA, Sportes C, Ahmadzadeh M, et al. IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother 2006; 29: 313-9. (Pubitemid 44297299)
14. Sereti I. Where have all the T cells gone? Blood 2009; 114:751-2.
15. Sportes C, Hakim FT, Memon SA, et al. Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med 2008; 205:1701-14. (Pubitemid 351962032)
16. Lelievre JD, Levy Y. Perspectives on interleukin-7 therapy in HIV infection. Curr Opin HIV AIDS 2007; 2:228-33. (Pubitemid 46941122)
17. Mackall CL, Fry TJ, Gress RE. Harnessing the biology of IL-7 for therapeutic application. Nat Rev Immunol 2011; 11:330-42.
18. Dion ML, Sekaly RP, Cheynier R. Estimating thymic function through quantification of T-cell receptor excision circles. Methods Mol Biol 2007; 380:197-213. (Pubitemid 350183330)
19. Marodon G, Desjardins D, Mercey L, et al. High diversity of the immune repertoire in humanized NOD.SCID.gamma c-/-mice. Eur J Immunol 2009; 39:2136-45.
20. Pasqual N, Gallagher M, Aude-Garcia C, et al. Quantitative and qualitative changes in V-J alpha rearrangements during mouse thymocyte differentiation: implication for a limited T cell receptor alpha chain repertoire. J Exp Med 2002; 196:1163-73. (Pubitemid 35304183)
21. Avettand-Fenoel V, Chaix ML, Blanche S, et al. LTR real-time PCR for HIV-1 DNA quantitation in blood cells for early diagnosis in infants born to seropositive mothers treated in HAART area (ANRS CO 01). J Med Virol 2009; 81:217-23.
22. Abrams D, Levy Y, Losso MH, et al. Interleukin-2 therapy in patients with HIV infection. N Engl J Med 2009; 361:1548-59.
23. Sereti I, Imamichi H, Natarajan V, et al. In vivo expansion of CD4CD45RO-CD25 T cells expressing foxP3 in IL-2-treated HIVinfected patients. J Clin Invest 2005; 115:1839-47. (Pubitemid 40979722)
24. Weiss L, Letimier FA, Carriere M, et al. In vivo expansion of naive and activated CD4+CD25+FOXP3+ regulatory T cell populations in interleukin-2-treated HIV patients. Proc Natl Acad Sci USA 2010; 107:10632-7.
25. Said EA, Dupuy FP, Trautmann L, et al. Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nat Med 2010; 16:452-9.
26. Sereti I, Dunham RM, Spritzler J, et al. IL-7 administration drives T cellcycle entry and expansion in HIV-1 infection. Blood 2009; 113:6304-14.
27. Sieg SF, Harding CV, Lederman MM. HIV-1 infection impairs cell cycle progression of CD4+ T cells without affecting early activation responses. J Clin Invest 2001; 108:757-64. (Pubitemid 32906205)
28. Sereti I, Anthony KB, Martinez-Wilson H, et al. IL-2-induced CD4+ T-cell expansion in HIV-infected patients is associated with long-term decreases in T-cell proliferation. Blood 2004; 104:775-80. (Pubitemid 38970572)
29. Kovacs JA, Lempicki RA, Sidorov IA, et al. Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients. J Clin Invest 2005; 115:2139-48. (Pubitemid 41134155)
30. Chomont N, El-Far M, Ancuta P, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 2009; 15:893-900.
31. Bruyand M, Thiebaut R, Lawson-Ayayi S, et al. Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort. Clin Infect Dis 2009; 49:1109-16.
32. Guiguet M, Boue F, Cadranel J, Lang JM, Rosenthal E, Costagliola D. Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): a prospective cohort study. Lancet Oncol 2009; 10:1152-9.
33. Lewden C, Chene G, Morlat P, et al. HIV-infected adults with a CD4 cell count greater than 500 cells/mm3 on long-term combination antiretroviral therapy reach same mortality rates as the general population. J Acquir Immune Defic Syndr 2007; 46: 72-7. (Pubitemid 47514615)