Immune Interventions In HIV Infection

Immunological Reviews

Volumn 254, Issue 1, 2013, Pages 355-371

  Carcelain, Guislaine ^a,b,c   Autran, Brigitte ^a,b,c  

^a SORBONNE UNIVERSITÉ   (France)

^b INSERM   (France)

^c PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

Author keywords

Cytokines; HIV; HIV cure; Immunotherapy; Therapeutic vaccines

Indexed keywords

DENDRITIC CELL VACCINE; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; INACTIVATED VACCINE; INTERLEUKIN 15; INTERLEUKIN 17; INTERLEUKIN 2; INTERLEUKIN 21; INTERLEUKIN 7; LIVE VACCINE; RECOMBINANT INTERLEUKIN 2;

ARTICLE; CD4 LYMPHOCYTE COUNT; CD4+ T LYMPHOCYTE; CELL FUNCTION; CELL PROLIFERATION; CELL SURVIVAL; CYTOKINE IMMUNOTHERAPY; DISEASE COURSE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOGENICITY; IMMUNOTHERAPY; IN VITRO STUDY; INFECTION CONTROL; NATURAL KILLER T CELL; PRIORITY JOURNAL; VIRUS IMMUNITY; VIRUS REPLICATION;

AIDS VACCINES; ANIMALS; CYTOKINES; HIV INFECTIONS; HUMANS; IMMUNOTHERAPY;

EID: 84879300903     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12083     Document Type: Article

References (160)

1. Autran B, et al. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 1997;277:112-116.
2. Palella FJ Jr, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998;338:853-860.
3. Guihot A, Bourgarit A, Carcelain G, Autran B. Immune reconstitution after a decade of combined antiretroviral therapies for human immunodeficiency virus. Trends Immunol 2011;32:131-137.
4. Mocroft A, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. Lancet 1998;352:1725-1730.
5. Finzi D, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 1999;5:512-517.
6. Autran B, Debre P, Walker B, Katlama C. Therapeutic vaccines against HIV need international partnerships. Nat Rev Immunol 2003;3:503-508.
7. International AIDS Society Scientific Working Group on HIV Cure, et al. Towards an HIV cure: a global scientific strategy. Nat Rev Immunol 2012;12:607-614.
8. Katlama C, et al. Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs. Lancet 2013. doi:doi:pii: S0140-6736(13)60104-X.10.1016/S0140-6736(13)60104-X
9. Jacobson EL, Pilaro F, Smith KA. Interleukin-2 infusions in HIV-infected patients. N Engl J Med 1997;336:1260-1261.
10. Koenig S, et al. Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression. Nat Med 1995;1:330-336.
11. Autran B, Carcelain G. AIDS. Boosting immunity to HIV-can the virus help? Science 2000;290:946-949.
12. Autran B, Carcelain G, Combadiere B, Debre P. Therapeutic vaccines for chronic infections. Science 2004;305:205-208.
13. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006;355:2283-2296.
14. Hütter G, et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 2009;360:692-698.
15. Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. The challenge of finding a cure for HIV infection. Science 2009;323:1304-1307.
16. Trono D, et al. HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science 2010;329:174-180.
17. Chêne G, et al. Changes in CD4+ cell count and the risk of opportunistic infection or death after highly active antiretroviral treatment. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine. AIDS 1998;12:2313-2320.
18. d'Arminio Monforte A, et al. CD4 cell counts at the third month of HAART may predict clinical failure. AIDS 1999;13:1669-1676.
19. MacMahon DK, et al. A phase I study of subcutaneous recombinant interleukin-2 in patients with advanced HIV-disease while on zidovudine. AIDS 1994;8:59-66.
20. Kovacs JA, et al. Controlled trial of interleukin-2 infusions in patients infected with the human immunodeficiency virus. N Engl J Med 1996;335:1350-1356.
21. Li TS, Tubiana R, Katlama C, Calvez V, Ait-Mohand H, Autran B. Long lasting recovery in CD4+ T cell function mirrors viral load reduction after highly active anti-retroviral therapy in patients with advanced HIV disease. Lancet 1998;351:1682-1686.
22. Lederman MM, et al. Cellular restoration in HIV infected persons treated with abacavir and a protease inhibitor: age inversely predicts naive CD4 count increase. AIDS 2000;14:2635-2642.
23. Renaud M, et al. Determinants of paradoxical CD4 cell reconstitution after protease inhibitor-containing antiretroviral regimen. AIDS 1999;13:669-676.
24. Grabar S, et al. Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy. Ann Intern Med 2000;133:401-410.
25. Ma A, Koka R, Burkett P. Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu Rev Immunol 2006;24:657-679.
26. Létourneau S, Krieg C, Pantaleo G, Boyman O. IL-2- and CD25-dependent immunoregulatory mechanisms in the homeostasis of T-cell subsets. J Allergy Clin Immunol 2009;123:758-762.
27. Brandenburg S, et al. IL-2 induces in vivo suppression by CD4(+)CD25(+)Foxp3(+) regulatory T cells. Eur J Immunol 2008;38:1643-1653.
28. Lane HC, Fauci AS. Immunologic abnormalities in the acquired immunodeficiency syndrome. Annu Rev Immunol 1985;3:477-500.
29. Dolan MJ, et al. In vitro T cell function, delayed-type hypersensitivity skin testing, and CD4+ T cell subset phenotyping independently predict survival time in patients infected with human immunodeficiency virus. J Infect Dis 1995;172:79-87.
30. Boudet F, Lecoeur H, Gougeon ML. Apoptosis associated with ex vivo down-regulation of Bcl-2 and up-regulation of Fas in potential cytotoxic CD8+ T lymphocytes during HIV infection. J Immunol 1996;156:2282-2293.
31. Davey RT Jr, et al. Subcutaneous administration of interleukin-2 in human immunodeficiency virus type 1-infected persons. J Infect Dis 1997;175:781-789.
32. Hengge UR, et al. Randomized, controlled phase II trial of subcutaneous interleukin-2 in combination with highly active antiretroviral therapy (HAART) in HIV patients. AIDS 1998;12:F225-F234.
33. Carr A, et al. 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 1998;178:992-999.
34. Davey RT Jr, et al. A randomized trial of high- versus low-dose subcutaneous interleukin-2 outpatient therapy for early human immunodeficiency virus type 1 infection. J Infect Dis 1999;179:849-858.
35. Levy Y, et al. Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial. ANRS 048 study group. Lancet 1999;353:1923-1929.
36. Losso MH, et al. A randomized, controlled, phase II trial comparing escalating doses of subcutaneous interleukin-2 plus antiretrovirals versus antiretrovirals alone in human immunodeficiency virus-infected patients with CD4+ cell counts >/=350/mm3. J Infect Dis 2000;181:1614-1621.
37. Levy Y, et al. Effects of interleukin-2 therapy combined with highly active antiretroviral therapy on immune restoration in HIV-1 infection: a randomized controlled trial. AIDS 2003;17:343-351.
38. Katlama C, et al. Interleukin-2 accelerates CD4 cell reconstitution in HIV-infected patients with severe immunosuppression despite highly active antiretroviral therapy: the ILSTIM study-ANRS 082. AIDS 2002;16:2027-2034.
39. Gougeon ML, et al. Immunological and virological effects of long term IL-2 therapy in HIV-1-infected patients. AIDS 2001;15:1729-1731.
40. Kovacs JA, et al. Interleukin-2 induced immune effects in human immunodeficiency virus-infected patients receiving intermittent interleukin-2 immunotherapy. Eur J Immunol 2001;31:1351-1360.
41. Porter BO, et al. Interleukin-2 cycling causes transient increases in high-sensitivity C-reactive protein and D-dimer that are not associated with plasma HIV-RNA levels. AIDS 2009;23:2015-2019.
42. Carcelain G, et al. Interleukin-2 therapy and thymic production of naive CD4 T cells in HIV-infected patients with severe CD4 lymphopenia. AIDS 2003;17:841-850.
43. Kovacs JA, et al. Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients. J Clin Invest 2005;115:2139-2148.
44. Marchetti G, et al. Low-dose prolonged intermittent interleukin-2 adjuvant therapy: results of a randomized trial among human immunodeficiency virus-positive patients with advanced immune impairment. J Infect Dis 2002;186:606-616.
45. + T cells in vivo after IL-2 treatment of patients with HIV infection. Proc Natl Acad Sci USA 2002;99:10712-10717.
46. Pandolfi F, et al. Low-dose IL-2 reduces lymphocyte apoptosis and increases naive CD4 cells in HIV-1 patients treated with HAART. Clin Immunol 2000;94:153-159.
47. Sereti I, et al. Long-term effects of intermittent interleukin 2 therapy in patients with HIV infection: characterization of a novel subset of CD4(+)/CD25(+) T cells. Blood 2002;100:2159-2167.
48. Sereti I, 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;104:775-780.
49. INSIGHT-ESPRIT Study Group; SILCAAT Scientific Committee. Interleukin-2 therapy in patients with HIV infection. N Engl J Med 2009;361:1548-1559.
50. Bolotin E, Smogorzewska M, Smith S, Widmer M, Weinberg K. Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7. Blood 1996;88:1887-1894.
51. Sudo T, et al. Interleukin 7 production and function in stromal cell-dependent B cell development. J Exp Med 1989;170:333-338.
52. Napolitano LA, et al. Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis. Nat Med 2001;7:73-79.
53. Fry TJ, Mackall CL. Interleukin-7: master regulator of peripheral T-cell homeostasis? Trends Immunol 2001;22:564-571.
54. Fry TJ, Mackall CL. What limits immune reconstitution in HIV infection? Divergent tools converge on thymic function. AIDS 2001;15:1881-1882.
55. Fry TJ, Mackall CL. The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance. J Immunol 2005;174:6571-6576.
56. Llano A, et al. Interleukin-7 in plasma correlates with CD4 T-cell depletion and may be associated with emergence of syncytium-inducing variants in human immunodeficiency virus type 1-positive individuals. J Virol 2001;75:10319-10325.
57. Beq S, Bugault F, Colle JH, Lambotte O, Delfraissy JF, Thèze J. Anti-retroviral therapy in HIV-infected patients: in vitro effects of AZT and saquinavir onthe response of CD4 and CD8 lymphocytes to interleukin-7. Eur Cytokine Netw 2005;16:293-299.
58. Beq S, et al. IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy. J Immunol 2006;176:914-922.
59. Mussini C, et al. Features of 'CD4-exploders', HIV-positive patients with an optimal immune reconstitution after potentantiretroviral therapy. AIDS 2002;16:1609-1616.
60. Pellegrini M, et al. IL-7 engages multiple mechanisms to overcome chronic viral infection and limit organ pathology. Cell 2011;144:601-613.
61. Levy Y, et al. Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest 2009;119:997-1007.
62. Sereti I, et al. IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Blood 2009;113:6304-6314.
63. Chun TW, et al. Effect of interleukin-2 on the pool of latently infected, resting CD4+ T cells in HIV-1-infected patients receiving highly active anti-retroviral therapy. Nat Med 1999;5:651-655.
64. Delaugerre C, et al. Increase of HIV-1 pro-viral DNA per million peripheral blood mononuclear cells in patients with advanced HIV disease (CD4 < 200 cells/mm3) receiving interleukin 2 combined with HAART versus HAART alone (ANRS-082 trial). Antivir Ther 2003;8:233-237.
65. Wang FX, et al. IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART. J Clin Invest 2005;115:128-137.
66. Managlia EZ, Landay A, Al-Harthi L. Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway. Virology 2006;350:443-452.
67. Smithgall MD, Wong JG, Critchett KE, Haffar OK. IL-7 up-regulates HIV-1 replication in naturally infected peripheral blood mononuclear cells. J Immunol 1996;156:2324-2330.
68. Vandergeeten C, et al. Interleukin-7 promotes HIV persistence during antiretroviral therapy. Blood 2013;121:4321-4329.
69. Schnittman SM, Lane HC, Greenhouse J, Justement JS, Baseler M, Fauci AS. Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals. Proc Natl Acad Sci USA 1990;87:6058-6062.
70. Chomont N, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 2009;15:893-900.
71. Descours B, et al. ALT ANRS CO15 Study Group. Immune responses driven by protective human leukocyte antigen alleles from long-term nonprogressors are associated with low HIV reservoir in central memory CD4 T cells. Clin Infect Dis 2012;54:1495-1503.
72. Sáez-Cirión A, et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI study. PLoS Pathog 2013;9:e1003211.
73. Ducrey-Rundquist O, Guyader M, Trono D. Modalities of interleukin-7-induced human immunodeficiency virus permissiveness in quiescent T lymphocytes. J Virol 2002;76:9103-9111.
74. Steffens CM, Managlia EZ, Landay A, Al-Harthi L. Interleukin-7-treated naive T cells can be productively infected by T-cell-adapted and primary isolates of human immunodeficiency virus 1. Blood 2002;99:3310-3318.
75. Poli G, Fauci AS. Cytokine modulation of HIV expression. Semin Immunol 1993;5:165-173.
76. Scripture-Adams DD, Brooks DG, Korin YD, Zack JA. Interleukin-7 induces expression of latent human immunodeficiency virus type 1 with minimal effects on T-cell phenotype. J Virol 2002;76:13077-13082.
77. Alderson MR, Sassenfeld HM, Widmer MB. Interleukin 7 enhances cytolytic T lymphocyte generation and induces lymphokine-activated killer cells from human peripheral blood. J Exp Med 1990;172:577-587.
78. Imamichi H, et al. HIV-1 viruses detected during episodic blips following interleukin-7 administration are similar to the viruses present before and after interleukin-7 therapy. AIDS 2011;25:159-164.
79. Lévy Y, et al. 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. Clin Infect Dis 2012;55:291-300.
80. Piketty C, et al. A high HIV DNA level in PBMCs at antiretroviral treatment interruption predicts a shorter time to treatment resumption, independently of the CD4 nadir. J Med Virol 2010;82:1819-1828.
81. Murphy RL, et al. A step ahead on the HIV collaboratory. Science 2009;324:1264-1265.
82. Cohen J. Breakthrough of the year. HIV treatment as prevention. Science 2011;334:1628.
83. Dalod M, et al. Evolution of cytotoxic T lymphocyte responses to human immunodeficiency virus type 1 in patients with symptomatic primary infection receiving antiretroviral triple therapy. J Infect Dis 1998;178:61-69.
84. Ogg GS, et al. Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy. J Virol 1999;73:797-800.
85. Rosenberg ES, et al. Vigorous HIV-1 specific CD4+ T cell responses associated with control of viremia. Science 1997;278:1447-1450.
86. Oxenius A, et al. Early highly active antiretroviral therapy for acute HIV infection preserves immune function of CD8+ and CD4+ T lymphocytes. Proc Natl Acad Sci USA 2000;97:3382-3387.
87. Plana M, Garcia F, Gallart T, Miró JM, Gatell JM. Lack of T-cell proliferative response to HIV-1 antigens after 1 year of highly active antiretroviral treatment in early HIV-1 disease. Immunology Study Group of Spanish EARTH-1 Study. Lancet 1998;352:1194-1195.
88. Ortiz GM, et al. Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects. Proc Natl Acad Sci USA 2001;98:13288-13293.
89. Carcelain G, et al. Transient mobilization of human immunodeficiency virus (HIV)-specific CD4 T-helper cells fails to control virus rebounds during intermittent antiretroviral therapy in chronic HIV type 1 infection. J Virol 2001;75:234-241.
90. Ruiz L, et al. HIV dynamics and T-cell immunity after three structured treatment interruptions in chronic HIV-1 infection. AIDS 2001;15:F19-F27.
91. Oxenius A, et al. Stimulation of HIV-specific cellular immunity by structured treatment interruption fails to enhance viral control in chronic HIV infection. Proc Natl Acad Sci USA 2002;99:13747-13752.
92. Allen TM, Kelleher AD, Zaunders J, Walker BD. STI and beyond: the prospects of boosting anti-HIV immune responses. Trends Immunol 2002;23:456-460.
93. Kinloch-de Loes S, Autran B. HIV-1 therapeutic vaccines. J Infect 2002;44:152-159.
94. Pantaleo G, Koup RA. Correlates of immune protection in HIV-1 infection: what we know, what we don't know, what we should know. Nat Med 2004;10:806-810.
95. Harrer T, et al. Cytotoxic T lymphocytes in asymptomatic long-term nonprogressing HIV-1 infection. Breadth and specificity of the response and relation to in vivo viral quasispecies in a person with prolonged infection and low viral load. J Immunol 1996;156:2616-2623.
96. Martinez V, et al. Combination of HIV-1-specific CD4 Th1 cell responses and IgG2 antibodies is the best predictor for persistence of long-term nonprogression. J Infect Dis 2005;191:2053-2063.
97. Migueles SA, et al. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat Immunol 2002;3:1061-1068.
98. Betts MR, et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 2006;107:4781-4789.
99. Xie J, et al. Distinct differentiation profile between HIV-Gag and Nef specific CD8+ T cells with preservation of CD27+ central memory T cells is dictated by HLA-B57/5801 and associated with virus control. AIDS 2010;24:2323-2329.
100. Appay V, et al. Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med 2002;8:379-385.
101. Almeida JR, et al. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med 2007;204:2473-2485.
102. Kiepiela P, et al. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med 2007;13:46-53.
103. Parren PW, Moore JP, Burton DR, Sattentau QJ. The neutralizing antibody response to HIV-1: viral evasion and escape from humoral immunity. AIDS 1999;13(Suppl):S137-S162.
104. Day CL, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 2006;443:350-354.
105. Trautmann L, et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med 2006;12:1198-1202. Erratum in: Nat Med 2006;12:1329.
106. McMichael AJ, Hanke T. HIV vaccines 1983-2003. Nat Med 2003;9:874-880.
107. Autran B, Costagliola D, Murphy R, Katlama C. Evaluating Therapeutic vaccines in patients infected with HIV. Expert Rev Vaccines 2004;3(Suppl):S169-S177.
108. Autran B, Kinloch S, Katlama C. Therapeutic immunization in HIV infection. Curr Opin HIV AIDS 2006;1:323-329.
109. Trkola A, et al. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat Med 2005;11:615-622.
110. McMichael AJ. HIV vaccines. Annu Rev Immunol 2006;24:227-255.
111. Goh LE, et al. The QUEST trial, a paradigm of HIV collaborative research. Nat Med 2000;6:1194.
112. Combadiere B, et al. Distinct time effects of vaccination on long-term proliferative and IFN-gamma-producing T cell memory to smallpox in humans. J Exp Med 2004;199:1585-1593.
113. Puissant-Lubrano B, et al. Influence of antigen exposure on the loss of long-term memory to childhood vaccines in HIV-infected patients. Vaccine 2009;27:3576-3578.
114. Tartaglia J, et al. Canarypox virus-based vaccines: prime-boost strategies to induce cell-mediated and humoral immunity against HIV. AIDS Res Hum Retroviruses 1998;14(Suppl):S291-S298.
115. Clements-Mann ML, et al. Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults. NIAID AIDS Vaccine Evaluation Group. J Infect Dis 1998;177:1230-1246.
116. Jin X, et al. Safety and immunogenicity of ALVAC vCP1452 and recombinant gp160 in newly human immunodeficiency virus type 1-infected patients treated with prolonged highly active antiretroviral therapy. J Virol 2002;76:2206-2216.
117. Markowitz M, et al. Discontinuation of antiretroviral therapy commenced early during the course of human immunodeficiency virus type 1 infection, with or without adjunctive vaccination. J Infect Dis 2002;186:634-643.
118. Kinloch-de Loes S, et al. Impact of therapeutic immunization on HIV-1 viremia after discontinuation of antiretroviral therapy initiated during acute infection. J Infect Dis 2005;192:607-617.
119. Samri A, et al. Multifunctional HIV-1 specific CD4 and CD8 T cell responses during a therapeutic immunization study (QUEST) in HAART-treated acutely-infected (PHI) Subjects Conference on Retroviruses and Opportunistic Infections (CROI), February 25-28, 2007; Los Angeles, CA, H-116.
120. Goujard C, et al. Interruption of antiretroviral therapy initiated during primary HIV-1 infection: impact of a therapeutic vaccination strategy combined with interleukin (IL)-2 compared with IL-2 alone in the ANRS 095 Randomized Study. AIDS Res Hum Retroviruses 2007;23:1105-1113.
121. Tubiana R, et al. Therapeutic immunization with a human immunodeficiency virus (HIV) type 1-recombinant canarypox vaccine in chronically HIV-infected patients: the Vacciter Study (ANRS 094). Vaccine 2005;23:4292-4301.
122. Lévy Y, et al. Immunological and virological efficacy of a therapeutic immunization combined with interleukin-2 in chronically HIV-1 infected patients. AIDS 2005;19:279-286.
123. Lévy Y, et al. Sustained control of viremia following therapeutic immunization in chronically HIV-1-infected individuals. AIDS 2006;20:405-413.
124. Kilby JM, et al. A phase II randomized, partially blinded trial of antiretroviral therapy (ART), HIV-specific immunization and IL-2 cycles to promote efficient control of viral replication (ACTG A5024). J Infect Dis 2006;194:1672-1676.
125. Tryniszewska E, et al. Vaccination of macaques with long-standing SIVmac251 infection lowers the viral set point after cessation of antiretroviral therapy. J Immunol 2002;169:5347-5357.
126. Autran B, et al. Greater viral rebound & reduced time to resume antretroviral therapy after therapeutic immunization with the ALVAC-HIV vaccine (vCP1452). AIDS 2008;22:1313-1322.
127. Papagno L, et al. Comprehensive analysis of virus-specific T-cells provides clues for the failure of therapeutic immunization with ALVAC-HIV vaccine. AIDS 2011;25:27-36.
128. Sutter G, Moss B. Nonreplicating vaccinia vector efficiently expresses recombinant genes. Proc Natl Acad Sci USA 1992;89:10847-10851.
129. Blanchard TJ, Alcami A, Andrea P, Smith GL. Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine. J Gen Virol 1998;79:1159-1167.
130. Drexler I, Heller K, Wahren B, Erfle V, Sutter G. Highly attenuated modified vaccinia virus Ankara replicates in baby hamster kidney cells, a potential host for virus propagation, but not in various human transformed and primary cells. J Gen Virol 1998;79:347-352.
131. Harrer E, et al. Therapeutic vaccination of HIV-1-infected patients on HAART with a recombinant HIV-1 nef-expressing MVA: safety, immunogenicity and influence on viral load during treatment interruption. Antivir Ther 2005;10:285-300.
132. Dorrell L, et al. Expansion and diversification of virus-specific T cells following immunization of human immunodeficiency virus type 1 (HIV-1)-infected individuals with a recombinant modified vaccinia virus Ankara/HIV-1 Gag vaccine. J Virol 2006;80:4705-4716.
133. Harari A, et al. NYVAC immunization induces polyfunctional HIV-specific T-cell responses in chronically-infected, ART-treated HIV patients. Eur J Immunol 2012;42:3038-3048.
134. Shiver JW, et al. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 2002;415:331-335.
135. Santra S, et al. Replication-defective adenovirus serotype 5 vectors elicit durable cellular and humoral immune responses in nonhuman primates. J Virol 2005;79:6516-6522.
136. Schooley RT, et al. AIDS clinical trials group 5197: a placebo-controlled trial of immunization of HIV-1-infected persons with a replication-deficient adenovirus type 5 vaccine expressing the HIV-1 core protein. J Infect Dis 2010;202:705-716.
137. Robbins GK, et al. Augmentation of HIV-1-specific T helper cell responses in chronic HIV-1 infection by therapeutic immunization. AIDS 2003;17:1121-1126.
138. Boström AC, et al. Long-term persistence of vaccination and HAART to human immunodeficiency virus (HIV). Vaccine 2004;22:1683-1691.
139. Dorrell L, et al. Therapeutic immunization of highly active antiretroviral therapy-treated HIV-1-infected patients: safety and immunogenicity of an HIV-1 gag/poly-epitope DNA vaccine. AIDS 2005;19:1321-1323.
140. MacGregor RR, et al. Plasmid vaccination of stable HIV-positive subjects on antiviral treatment results in enhanced CD8 T-cell immunity and increased control of viral "blips". Vaccine 2005;23:2066-2073.
141. Casazza JP, et al. Therapeutic vaccination expands and improves the function of the HIV-specific memory T-cell repertoire. J Infect Dis 2013. doi:10.1093/infdis/jit098
142. Tsunetsugu-Yokota Y, et al. Yeast-derived human immunodeficiency virus type 1p55(gag) virus-like particles activate dendritic cells (DCs) and induce perforin expression in gag-Specific CD8(+) T Cells by Cross-Presentation of DCs. J Virol 2003;77:10250-10259.
143. Lu W, Arraes L, Ferreira W, Andrieu JM. Therapeutic dendritic-cell vaccine for chronic HIV-1 infection. Nat Med 2004;10:1359-1365.
144. García F, et al. Therapeutic immunization with dendritic cells loaded with inactivated autologous HIV-1 in chronic HIV-1 infected patients. J Infect Dis 2005;195:1680-1685.
145. Garcia F, et al. A therapeutic dendritic cell-based vaccine for HIV-1 infection. J Infect Dis 2011;203:473-478.
146. Ide F, et al. Peptide-loaded dendritic-cell vaccination followed by treatment interruption for chronic HIV-1 infection: a phase 1 trial. J Med Virol 2006;78:711-718.
147. Gandhi RT, et al. A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapy. Vaccine 2009;27:6088-6094.
148. Routy JP, et al. Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy. Clin Immunol 2010;134:140-147.
149. Lisziewicz J, et al. Control of viral rebound through therapeutic immunization with DermaVir. AIDS 2005;19:35-43.
150. Lisziewicz J, et al. Single DermaVir immunization: dose-dependent expansion of precursor/memory T cells against all HIV antigens in HIV-1 infected individuals. PLoS ONE 2012;7:e35416.
151. Combadière B, et al. Preferential amplification of CD8 effector-T cells after transcutaneous application of an inactivated influenza vaccine: a randomized phase I trial. PLoS ONE 2010;5:e10818.
152. Avettand-Fenoel V, et al. HIV-DNA in rectal cells is well correlated with HIV-DNA in blood in different groups of patients, including long-term nonprogressors. AIDS 2008;22:1880-1882.
153. Autran B, Descours B, Avettand-Fenoel V, Rouzioux C. Elite controllers as a model of functional cure. Curr Opin HIV AIDS 2011;6:181-187.
154. Dalmasso C, et al. Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study. PLoS ONE 2008;3:e3907.
155. Yukl SA, et al. Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy. AIDS 2010;24:2451-2460.
156. Autran B, Descours B, Bacchus C. Immune control of HIV-1 reservoirs. Curr Opin HIV AIDS 2013;8:204-210.
157. Persaud D, et al. Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4R T-cell latent HIV reservoir. AIDS 2011;25:2227-2234.
158. Shan L, et al. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 2012;36:491-501.
159. Shete A, et al. HIV antigen-specific reactivation of HIV infection from cellular reservoirs: implications in the settings of therapeutic vaccinations. AIDS Res Hum Retroviruses 2012;28:835-843.
160. Walensky RP, et al. A therapeutic HIV vaccine: how good is good enough? Vaccine 2004;22:4044-4053.