• 1
    Grabar S, Le Moing V, Goujard C 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; 133:401410.
  • 2
    Piketty C, Weiss L, Thomas F, Mohamed AS, Belec L, Kazatchkine MD. Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen. J Infect Dis 2001; 183:13281335.
  • 3
    Gilson RJ, Man SL, Copas A et al. Discordant responses on starting highly active antiretroviral therapy: suboptimal CD4 increases despite early viral suppression in the UK Collaborative HIV Cohort (UK CHIC) Study. HIV Med 2010; 11:152160.
  • 4
    Gaardbo JC, Hartling HJ, Gerstoft J, Nielsen SD. Incomplete immune recovery in HIV infection: mechanisms, relevance for clinical care, and possible solutions. Clin Dev Immunol 2012; 2012:670957.
  • 5
    Li T, Wu N, Dai Y et al. Reduced thymic output is a major mechanism of immune reconstitution failure in HIV-infected patients after long-term antiretroviral therapy. Clin Infect Dis 2005; 53:944951.
  • 6
    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; 46:7277.
  • 7
    Rodger AJ, Lodwick R, Schechter M et al. Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS 2013; 27:973979.
  • 8
    Levacher M, Hulstaert F, Tallet S, Ullery S, Pocidalo JJ, Bach BA. The significance of activation markers on CD8 lymphocytes in human immunodeficiency syndrome: staging and prognostic value. Clin Exp Immunol 1992; 90:376382.
  • 9
    Hunt PW. HIV and inflammation: mechanisms and consequences. Curr HIV/AIDS Rep 2012; 9:139147.
  • 10
    Marziali M, De Santis W, Carello R et al. T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART. AIDS 2006; 20:20332041.
  • 11
    Erikstrup C, Kronborg G, Lohse N, Ostrowski SR, Gerstoft J, Ullum H. T-cell dysfunction in HIV-1-infected patients with impaired recovery of CD4 cells despite suppression of viral replication. J Acquir Immune Defic Syndr 2010; 53:303310.
  • 12
    Delobel P, Nugeyre MT, Cazabat M et al. Naive T-cell depletion related to infection by X4 human immunodeficiency virus type 1 in poor immunological responders to highly active antiretroviral therapy. J Virol 2006; 80:1022910236.
  • 13
    Nakanjako D, Ssewanyana I, Mayanja-Kizza H et al. High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort. BMC Infect Dis 2011; 11:43.
  • 14
    Mendez-Lagares G, del Pozo Balado Mdel M, Genebat Gonzalez M, Perganeda Sanchez AG, Leal Noval M, Pacheco Lopez YM. Severe immune dysregulation affects CD4(+)CD25(hi)FoxP3(+) regulatory T cells in HIV-infected patients with low-level CD4 T-cell repopulation despite suppressive highly active antiretroviral therapy. J Infect Dis 2012; 205:15011509.
  • 15
    Mendez-Lagares G, Garcia-Perganeda A, Pozo-Balado M et al. Differential alterations of the CD4 and CD8 T cell subsets in HIV-infected patients on highly active antiretroviral therapy with low CD4 T cell restoration. J Antimicrob Chemother 2012; 67:12281237.
  • 16
    Doyle T, Smith C, Vitiello P et al. Plasma HIV-1 RNA detection below 50 copies/ml and risk of virologic rebound in patients receiving highly active antiretroviral therapy. Clin Infect Dis 2012; 54:724732.
  • 17
    Maggiolo F, Callegaro A, Cologni G et al. Ultrasensitive assessment of residual low-level HIV viremia in HAART-treated patients and risk of virological failure. J Acquir Immune Defic Syndr 2012; 60:473482.
  • 18
    Gianotti N, Galli L, Racca S et al. Residual viraemia does not influence 1 year virological rebound in HIV-infected patients with HIV RNA persistently below 50 copies/mL. J Antimicrob Chemother 2012; 67:213217.
  • 19
    Bastard JP, Soulie C, Fellahi S et al. Circulating interleukin-6 levels correlate with residual HIV viraemia and markers of immune dysfunction in treatment-controlled HIV-infected patients. Antivir Ther 2012; 17:915919.
  • 20
    Widdrington J, Payne B, Medhi M, Valappil M, Schmid ML. The significance of very low-level viraemia detected by sensitive viral load assays in HIV infected patients on HAART. J Infect 2011; 62:8792.
  • 21
    Charpentier C, Landman R, Laouenan C et al. Persistent low-level HIV-1 RNA between 20 and 50 copies/mL in antiretroviral-treated patients: associated factors and virological outcome. J Antimicrob Chemother 2012; 67:22312235.
  • 22
    Ostrowski SR, Katzenstein TL, Thim PT, Pedersen BK, Gerstoft J, Ullum H. Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy. J Infect Dis 2005; 191:348357.
  • 23
    Fazekas de St Groth B, Landay AL. Regulatory T cells in HIV infection: pathogenic or protective participants in the immune response? AIDS 2008; 22:671683.
  • 24
    Kassiotis G, O'Garra A. Immunology. Immunity benefits from a little suppression. Science 2008; 320:11681169.
  • 25
    Lund JM, Hsing L, Pham TT, Rudensky AY. Coordination of early protective immunity to viral infection by regulatory T cells. Science 2008; 320:12201224.
  • 26
    Moreno-Fernandez ME, Presicce P, Chougnet CA. Homeostasis and function of regulatory T cells in HIV/SIV infection. J Virol 2012; 86:1026210269.
  • 27
    Horta A, Nobrega C, Amorim-Machado P et al. Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T cells. PLOS ONE 2013; 8:e57336.
  • 28
    Foxall RB, Albuquerque AS, Soares RS et al. Memory and naive-like regulatory CD4+ T cells expand during HIV-2 infection in direct association with CD4+ T-cell depletion irrespectively of viremia. AIDS 2011; 25:19611970.
  • 29
    Nilsson J, Boasso A, Velilla PA et al. HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood 2006; 108:38083817.
  • 30
    Tenorio AR, Martinson J, Pollard D, Baum L, Landay A. The relationship of T-regulatory cell subsets to disease stage, immune activation, and pathogen-specific immunity in HIV infection. J Acquir Immune Defic Syndr 2008; 48:577580.
  • 31
    Lim A, Tan D, Price P et al. Proportions of circulating T cells with a regulatory cell phenotype increase with HIV-associated immune activation and remain high on antiretroviral therapy. AIDS 2007; 21:15251534.
  • 32
    Del Pozo-Balado Mdel M, Leal M, Mendez-Lagares G, Pacheco YM. CD4(+)CD25(+/hi)CD127(lo) phenotype does not accurately identify regulatory T cells in all populations of HIV-infected persons. J Infect Dis 2010; 201:331335.
  • 33
    Sachdeva M, Fischl MA, Pahwa R, Sachdeva N, Pahwa S. Immune exhaustion occurs concomitantly with immune activation and decrease in regulatory T cells in viremic chronically HIV-1-infected patients. J Acquir Immune Defic Syndr 2010; 54:447454.
  • 34
    Chase AJ, Yang HC, Zhang H, Blankson JN, Siliciano RF. Preservation of FoxP3+ regulatory T cells in the peripheral blood of human immunodeficiency virus type 1-infected elite suppressors correlates with low CD4+ T-cell activation. J Virol 2008; 82:83078315.
  • 35
    Jiao Y, Fu J, Xing S et al. The decrease of regulatory T cells correlates with excessive activation and apoptosis of CD8+ T cells in HIV-1-infected typical progressors, but not in long-term non-progressors. Immunology 2009; 128:e366375.
  • 36
    Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 2010; 10:490500.
  • 37
    Saison J, Tardy JC, Scholtes C et al. Low-level viremia is associated with non-B subtypes in patients infected with HIV with virological success following HAART introduction. J Med Virol 2013; 85:953958.
  • 38
    Demaret J, Saison J, Venet F et al. Assessment of a novel flow cytometry technique of one-step intracellular staining: example of FOXP3 in clinical samples. Cytometry B Clin Cytom 2013; 84:187193.
  • 39
    Piconi S, Trabattoni D, Gori A et al. Immune activation, apoptosis, and Treg activity are associated with persistently reduced CD4+ T-cell counts during antiretroviral therapy. AIDS 2010; 24:19912000.
  • 40
    Andrade RM, Hygino J, Kasahara TM et al. High IL-10 production by aged AIDS patients is related to high frequency of Tr-1 phenotype and low in vitro viral replication. Clin Immunol 2012; 145:3143.
  • 41
    Casotti JA, Passos LN, Oliveira FJ, Cerutti C, Jr. Factors associated with paradoxical immune response to antiretroviral therapy in HIV infected patients: a case control study. BMC Infect Dis 2011; 11:306.
  • 42
    Arguello RJ, Balbaryski J, Barboni G, Candi M, Gaddi E, Laucella S. Altered frequency and phenotype of CD4+ forkhead box protein 3+ T cells and its association with autoantibody production in human immunodeficiency virus-infected paediatric patients. Clin Exp Immunol 2012; 168:224233.
  • 43
    Negredo E, Massanella M, Puig J et al. Nadir CD4 T cell count as predictor and high CD4 T cell intrinsic apoptosis as final mechanism of poor CD4 T cell recovery in virologically suppressed HIV-infected patients: clinical implications. Clin Infect Dis 2010; 50:13001308.
  • 44
    Le T, Wright EJ, Smith DM et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med 2013; 368:218230.
  • 45
    Gaardbo JC, Nielsen SD, Vedel SJ et al. Regulatory T cells in human immunodeficiency virus-infected patients are elevated and independent of immunological and virological status, as well as initiation of highly active anti-retroviral therapy. Clin Exp Immunol 2008; 154:8086.
  • 46
    Kared H, Lelievre JD, Donkova-Petrini V et al. HIV-specific regulatory T cells are associated with higher CD4 cell counts in primary infection. AIDS 2008; 22:24512460.
  • 47
    Saison J, Demaret J, Venet F et al. CD4+CD25+CD127- assessment as a surrogate phenotype for FOXP3+ regulatory T cells in HIV-1 infected viremic and aviremic subjects. Cytometry B Clin Cytom 2012; 84:5054.
  • 48
    Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003; 4:330336.
  • 49
    Belkaid Y, Rouse BT. Natural regulatory T cells in infectious disease. Nat Immunol 2005; 6:353360.
  • 50
    Simonetta F, Lecuroux C, Girault I et al. Early and long-lasting alteration of effector CD45RA(-)Foxp3(high) regulatory T-cell homeostasis during HIV infection. J Infect Dis 2012; 205:15101519.
  • 51
    Hodi FS, Butler M, Oble DA et al. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci USA 2008; 105:30053010.
  • 52
    Colombo MP, Piconese S. Regulatory-T-cell inhibition versus depletion: the right choice in cancer immunotherapy. Nat Rev Cancer 2007; 7:880887.
  • 53
    Girard PM, Katlama C, Pialoux G. VIH. DOIN Editors. Rueil-Malmaison, France: Wolters Kluwer France, 2011.
  • 54
    Li T, Wu N, Dai Y et al. Reduced thymic output is a major mechanism of immune reconstitution failure in HIV-infected patients after long-term antiretroviral therapy. Clin Infect Dis 2011; 53:944951.
  • 55
    Benito JM, Lopez M, Lozano S et al. Differential upregulation of CD38 on different T-cell subsets may influence the ability to reconstitute CD4+ T cells under successful highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2005; 38:373381.
  • 56
    Tiba F, Nauwelaers F, Traore S et al. Immune reconstitution during the first year of antiretroviral therapy of HIV-1-infected adults in rural Burkina Faso. Open AIDS J 2012; 6:1625.
  • 57
    Freguja R, Gianesin K, Mosconi I et al. Regulatory T cells and chronic immune activation in human immunodeficiency virus 1 (HIV-1)-infected children. Clin Exp Immunol 2011; 164:373380.
  • 58
    Shaw JM, Hunt PW, Critchfield JW et al. Increased frequency of regulatory T cells accompanies increased immune activation in rectal mucosae of HIV-positive noncontrollers. J Virol 2011; 85:1142211434.
  • 59
    Hunt PW, Landay AL, Sinclair E et al. A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers. PLOS ONE 2011; 6:e15924.
  • 60
    Prendergast A, O'Callaghan M, Menson E et al. Factors influencing T cell activation and programmed death 1 expression in HIV-infected children. AIDS Res Hum Retroviruses 2012; 28:465468.
  • 61
    Rallon NI, Lopez M, Soriano V et al. Level, phenotype and activation status of CD4+FoxP3+ regulatory T cells in patients chronically infected with human immunodeficiency virus and/or hepatitis C virus. Clin Exp Immunol 2009; 155:3543.