Incomplete immune recovery in HIV infection: Mechanisms, relevance for clinical care, and possible solutions

Clinical and Developmental Immunology

Volumn 2012, Issue , 2012, Pages

  Gaardbo, Julie C ^a   Hartling, Hans J ^a   Gerstoft, Jan ^a   Nielsen, Susanne D ^a  

^a Rigshospitalet   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CD28 ANTIGEN; CD31 ANTIGEN; CD4 ANTIGEN; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CCR5 ANTAGONIST; CHEMOKINE RECEPTOR CXCR4; CYCLOOXYGENASE 2 INHIBITOR; ENFUVIRTIDE; GRANULOCYTE COLONY STIMULATING FACTOR; GROWTH HORMONE RELEASING FACTOR; HUMAN IMMUNODEFICIENCY VIRUS FUSION INHIBITOR; IMMUNOGLOBULIN; INTEGRASE INHIBITOR; INTERLEUKIN 15; INTERLEUKIN 17; INTERLEUKIN 2; INTERLEUKIN 6; INTERLEUKIN 7; INTERLEUKIN 7 RECEPTOR; PALIFERMIN; PROSTAGLANDIN SYNTHASE INHIBITOR; RALTEGRAVIR; RECOMBINANT GROWTH HORMONE; RECOMBINANT INTERLEUKIN 15; RECOMBINANT INTERLEUKIN 2; RECOMBINANT INTERLEUKIN 7; RECOMBINANT KERATINOCYTE GROWTH FACTOR; T LYMPHOCYTE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; UNINDEXED DRUG; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

ADD ON THERAPY; ALCOHOL CONSUMPTION; APOPTOSIS; ARTHRALGIA; BACTERIAL TRANSLOCATION; BONE MARROW; CANCER GROWTH; CD4 LYMPHOCYTE COUNT; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL DIVISION; CELL EXPANSION; CELL MIGRATION; COMORBIDITY; COMPUTER ASSISTED TOMOGRAPHY; CYTOKINE PRODUCTION; CYTOMEGALOVIRUS INFECTION; DISEASE COURSE; DRUG ABUSE; DRUG EFFECT; DRUG MEGADOSE; GLUCOSE INTOLERANCE; HEMATOPOIETIC STEM CELL; HEPATITIS B; HEPATITIS C; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HIV ASSOCIATED DEMENTIA; HOST RESISTANCE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME; IMMUNE SYSTEM; IMMUNOSUPPRESSIVE TREATMENT; LIPODYSTROPHY; LYMPHOCYTOPOIESIS; MEMORY CELL; MIXED INFECTION; MORBIDITY; MORTALITY; PATIENT CARE; PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMOCYSTIS PNEUMONIA; POVERTY; PREMEDICATION; PRIORITY JOURNAL; PROSPECTIVE STUDY; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REGULATORY T LYMPHOCYTE; REVIEW; SENESCENCE; SINGLE DRUG DOSE; SMOKING; T CELL DEPLETION; T LYMPHOCYTE ACTIVATION; TH17 CELL; THYMUS; TREATMENT DURATION; VIRUS LOAD; VIRUS REPLICATION; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; PATHOLOGY; TREATMENT FAILURE; VIROLOGY;

ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; APOPTOSIS; CD4 LYMPHOCYTE COUNT; HIV; HIV INFECTIONS; HUMANS; INTERLEUKIN-7; LYMPHOCYTE ACTIVATION; T-LYMPHOCYTES, REGULATORY; TH17 CELLS; TREATMENT FAILURE; VIRAL LOAD; VIRUS REPLICATION;

EID: 84859716392     PISSN: 17402522     EISSN: 17402530     Source Type: Journal    
DOI: 10.1155/2012/670957     Document Type: Review

References (213)

1. Pakker N. G., Notermans D. W., De Boer R. J., Roos M. T. L., De Wolf F., Hill A., Leonard J. M., Danner S. A., Miedema F., Schellekens P. T. A., Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation Nature Medicine 1998 4 2 208 214 (Pubitemid 28137376)
2. Autran B., Carcelaint G., Li T. S., Gorochov G., Blanc C., Renaud M., Durali M., Mathez D., Calvez V., Leibowitch J., Katlama C., Debré P., Restoration of the immune system with anti-retroviral therapy Immunology Letters 1999 66 1-3 207 211 (Pubitemid 29136840)
3. Mocroft A., Phillips A., Gatell J., Ledergerber B., Fisher M., Clumeck N., Losso M., Lazzarin A., Fatkenheuer G., Lundgren J., Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study Lancet 2007 370 9585 407 413 (Pubitemid 47176633)
4. Piketty C., Castiel P., Belec L., Batisse D., Mohamed A. S., Gilquin J., Gonzalez-Canali G., Jayle D., Karmochkine M., Weiss L., Aboulker J. P., Kazatchkine M. D., Discrepant responses to triple combination antiretroviral therapy in advanced HIV disease AIDS 1998 12 7 745 750 (Pubitemid 28190697)
5. Autran B., Carcelain G., Li T. S., Blanc C., Mathez D., Tubiana R., Katlama C., Debré P., Leibowitch J., Positive effects of combined antiretroviral therapy on CD4 + T cell homeostasis and function in advanced HIV disease Science 1997 277 5322 112 116 (Pubitemid 27450659)
6. Marziali M., De Santis W., Carello R., Leti W., Esposito A., Isgr A., Fimiani C., Sirianni M. C., Mezzaroma I., Aiuti F., T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART AIDS 2006 20 16 2033 2041 (Pubitemid 44611056)
7. Erikstrup C., Kronborg G., Lohse N., Rye O. S., Gerstoft J., Ullum H., T-cell dysfunction in HIV-1-infected patients with impaired recovery of CD4 cells despite suppression of viral replication Journal of Acquired Immune Deficiency Syndromes 2010 53 3 303 310
8. Marchetti G., Gazzola L., Trabattoni D., Bai F., Ancona G., Ferraris L., Meroni L., Galli M., Clerici M., Gori A., D'Arminio Monforte A., Skewed T-cell maturation and function in HIV-infected patients failing CD4 + recovery upon long-term virologically suppressive HAART AIDS 2010 24 10 1455 1460
9. Li T., Wu N., Dai Y., Qiu Z., Han Y., Xie J., Zhu T., Li Y., Reduced thymic output is a major mechanism of immune reconstitution failure in HIV-infected patients after long-term antiretroviral therapy Clinical Infectious Diseases 2011 53 9 944 951
10. Lewden C., Chne G., Morlat P., Raffi F., Dupon M., Dellamonica P., Pellegrin J.-L., Katlama C., Dabis F., Leport C., Leport C., Raffi F., Chne G., Salamon R., Moatti J-P., Pierret J., Spire B., Brun-Vézinet F., Fleury H., Masquelier B., Peytavin G., Garraffo R., Chne G., Dabis F., Lewden C., Lawson-Ayayi S., Thiébaut R., Winnock M., Dupon M., Mercié P., Moreau J. F., Morlat P., Pellegrin J. L., Ragnaud J. M., Neau D., Bernard N., Lacoste D., Malvy D., Moreau J.-F., Blanco P., Fleury H., Lafon M. E., Masquelier B., Pellegrin I., Miremont G., Breilh D., HIV-infected adults with a CD4 cell count greater than 500 cells/mm 3 on long-term combination antiretroviral therapy reach same mortality rates as the general population Journal of Acquired Immune Deficiency Syndromes 2007 46 1 72 77 (Pubitemid 47514615)
11. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies Lancet 2008 372 9635 293 299
12. Piketty C., Weiss L., Thomas F., Mohamed A. S., Belec L., Kazatchkine M. D., Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen Journal of Infectious Diseases 2001 183 9 1328 1335 (Pubitemid 32337114)
13. Engsig F. N., Gerstoft J., Kronborg G., Larsen C. S., Pedersen G., Roge B. T., Jensen J., Nielsen L. N., Obel N., Long-term mortality in HIV patients virally suppressed for more than three years with incomplete CD4 recovery: a cohort study BMC Infectious Diseases 2010 318
14. Moore R. D., Keruly J. C., CD4 + cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression Clinical Infectious Diseases 2007 44 3 441 446 (Pubitemid 46147630)
15. D'Amico R., Yang Y., Mildvan D., Evans S. R., Schnizlein-Bick C. T., Hafner R., Webb N., Basar M., Zackin R., Jacobson M. A., Lower CD4 + T lymphocyte nadirs may indicate limited immune reconstitution in HIV-1 infected individuals on potent antiretroviral therapy: analysis of immunophenotypic marker results of AACTG 5067 Journal of Clinical Immunology 2005 25 2 106 115 (Pubitemid 40576722)
16. Kaufmann G. R., Furrer H., Ledergerber B., Perrin L., Opravil M., Vernazza P., Cavassini M., Bernasconi E., Rickenbach M., Battegay M., Characteristics, determinants, and clinical relevance of CD4 T cell recovery to 500 cells/ L in HIV type 1-infected individuals receiving potent antiretroviral therapy Clinical Infectious Diseases 2005 41 3 361 372 (Pubitemid 41022115)
17. Greub G., Ledergerber B., Battegay M., Grob P., Perrin L., Furrer H., Burgisser P., Erb P., Boggian K., Piffaretti J. C., Hirschel B., Janin P., Francioli P., Flepp M., Telenti A., Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the swiss HIV cohort study Lancet 2000 356 9244 1800 1805
18. Kolte L., Strandberg C., Dreves A. M., Ersbll A. K., Jeppesen D. L., Ryder L. P., Nielsen S. D., Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings Scandinavian Journal of Infectious Diseases 2002 34 9 668 672
19. Kolte L., Dreves A. M., Ersbll A. K., Strandberg C., Jeppesen D. L., Nielsen J. O., Ryder L. P., Nielsen S. D., Association between larger thymic size and higher thymic output in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy Journal of Infectious Diseases 2002 185 11 1578 1585 (Pubitemid 34587519)
20. Vigano A., Vella S., Principi N., Bricalli D., Sala N., Salvaggio A., Saresella M., Vanzulli A., Clerici M., Thymus volume correlates with the progression of vertical HIV infection AIDS 1999 13 5 F29 F34
21. Douek D. C., Vescio R. A., Betts M. R., Brenchley J. M., Hill B. J., Zhang L., Berenson J. R., Collins R. H., Koup R. A., Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution Lancet 2000 355 9218 1875 1881 (Pubitemid 30311880)
22. Haynes B. F., Markert M. L., Sempowski G. D., Patel D. D., Hale L. P., The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection Annual Review of Immunology 2000 18 529 560 (Pubitemid 30365390)
23. McCune J. M., Loftus R., Schmidt D. K., Carroll P., Webster D., Swor-Yim L. B., Francis I. R., Gross B. H., Grant R. M., High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection Journal of Clinical Investigation 1998 101 11 2301 2308 (Pubitemid 28270424)
24. Smith K. Y., Valdez H., Landay A., Spritzler J., Kessler H. A., Connick E., Kuritzkes D., Gross B., Francis I., McCune J. M., Lederman M. M., Thymic size and lymphocyte restoration in patients with human immunodeficiency virus infection after 48 weeks of zidovudine, lamivudine, and ritonavir therapy Journal of Infectious Diseases 2000 181 1 141 147 (Pubitemid 30049042)
25. Jamieson B. D., Douek D. C., Killian S., Hultin L. E., Scripture-Adams D. D., Giorgi J. V., Marelli D., Koup R. A., Zack J. A., Generation of functional thymocytes in the human adult Immunity 1999 10 5 569 575 (Pubitemid 29262659)
26. Khoury G., Rajasuriar R., Cameron P. U., Lewin S. R., The role of nave T-cells in HIV-1 pathogenesis: an emerging key player Clinical Immunology 2011 141 3 253 267
27. Kimmig S., Przybylski G. K., Schmidt C. A., Laurisch K., Mwes B., Radbruch A., Thiel A., Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood Journal of Experimental Medicine 2002 195 6 789 794 (Pubitemid 34259723)
28. Junge S., Kloeckener-Gruissem B., Zufferey R., Keisker A., Salgo B., Fauchere J. C., Scherer F., Shalaby T., Grotzer M., Siler U., Seger R., Gngr T., Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4 + T cells in normal individuals during aging and in lymphopenic children European Journal of Immunology 2007 37 11 3270 3280 (Pubitemid 350131305)
29. Hazenberg M. D., Otto S. A., Stuart J. W. T. C., Verschuren M. C. M., Borleffs J. C. C., Boucher C. A. B., Coutinho R. A., Lange J. M. A., De Wit T. F. R., Tsegaye A., Van Dongen J. J. M., Hamann D., De Boer R. J., Miedema F., Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection Nature Medicine 2000 6 9 1036 1042
30. Douek D. C., McFarland R. D., Keiser P. H., Gage E. A., Massey J. M., Haynes B. F., Polis M. A., Haase A. T., Feinberg M. B., Sullivan J. L., Jamieson B. D., Zack J. A., Picker L. J., Koup R. A., Changes in thymic function with age and during the treatment of HIV infection Nature 1998 396 6712 690 695 (Pubitemid 29003949)
31. Zhang L., Lewin S. R., Markowitz M., Lin H. H., Skulsky E., Karanicolas R., Yuxian H., Xia J., Tuttleton S., Vesanen M., Spiegel H., Kost R., Van Lunzen J., Stellbrink H. J., Wolinsky S., Borkowsky W., Palumbo P., Kostrikis L. G., Ho D. D., Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy Journal of Experimental Medicine 1999 190 5 725 732 (Pubitemid 29428654)
32. Vrisekoop N., Van Gent R., De Boer A. B., Otto S. A., Borleffs J. C. C., Steingrover R., Prins J. M., Kuijpers T. W., Wolfs T. F. W., Geelen S. P. M., Vulto I., Lansdorp P., Tesselaar K., Borghans J. A. M., Miedema F., Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging Journal of Immunology 2008 181 2 1573 1581
33. Tanaskovic S., Fernandez S., French M. A., Price R. I., Song S., Robins P. D., Price P., Thymic tissue is not evident on high-resolution computed tomography and [18F]Fluoro-deoxy-glucose positron emission tomography scans of aviraemic HIV patients with poor recovery of CD4 + T cells AIDS 2011 25 9 1235 1237
34. Isgr A., Leti W., De Santis W., Marziali M., Esposito A., Fimiani C., Luzi G., Pinti M., Cossarizza A., Aiuti F., Mezzaroma I., Altered clonogenic capability and stromal cell function characterize bone marrow of HIV-infected subjects with low CD4 + T cell counts despite viral suppression during HAART Clinical Infectious Diseases 2008 46 12 1902 1910
35. Delobel P., Nugeyre M. T., Cazabat M., Sandres-Sauné K., Pasquier C., Cuzin L., Marchou B., Massip P., Cheynier R., Barré-Sinoussi F., Izopet J., Isral N., Nave T-cell depletion related to infection by X4 human immunodeficiency virus type 1 in poor immunological responders to highly active antiretroviral therapy Journal of Virology 2006 80 20 10229 10236 (Pubitemid 44522616)
36. Marchetti G., Gori A., Casabianca A., Magnani M., Franzetti F., Clerici M., Perno C. F., Monforte A. D. A., Galli M., Meroni L., Comparative analysis of T-cell turnover and homeostatic parameters in HIV-infected patients with discordant immune-virological responses to HAART AIDS 2006 20 13 1727 1736 (Pubitemid 44299364)
37. Kolte L., Ryder L. P., Albrecht-Beste E., Jensen F. K., Nielsen S. D., HIV-infected patients with a large thymus maintain higher CD4 counts in a 5-year follow-up study of patients treated with highly active antiretroviral therapy Scandinavian Journal of Immunology 2009 70 6 608 613
38. Molina-Pinelo S., Vivancos J., De Felipe B., Soriano-Sarabia N., Valladares A., De La Rosa R., Vallejo A., Leal M., Thymic volume predicts CD4 T-cell decline in HIV-infected adults under prolonged treatment interruption Journal of Acquired Immune Deficiency Syndromes 2006 42 2 203 206 (Pubitemid 43884715)
39. Garca F., Plana M., Mestre G., Arnedo M., Gil C., Mir J. M., Cruceta A., Pumarola T., Gallart T., Gatell J. M., Immunological and virological factors at baseline may predict response to structured therapy interruption in early stage chronic HIV-1 infection AIDS 2002 16 13 1761 1765
40. Van Gent R., Schadenberg A. W.L., Otto S. A., Nievelstein R. A.J., Sieswerda G. T., Haas F., Miedema F., Tesselaar K., Jansen N. J.G., Borghans J. A.M., Long-term restoration of the human T-cell compartment after thymectomy during infancy: a role for thymic regeneration? Blood 2011 118 3 627 634
41. Htter G., Ganepola S., Eradication of HIV by transplantation of CCR5-deficient hematopoietic stem cells The Scientific World Journal 2011 11 1068 1076
42. Marandin A., Katz A., Oksenhendler E., Tulliez M., Picard F., Vainchenker W., Louache F., Loss of primitive hematopoietic progenitors in patients with human immunodeficiency virus infection Blood 1996 88 12 4568 4578 (Pubitemid 26419139)
43. Moses A., Nelson J., Bagby G. C., The influence of human immunodeficiency virus-1 on hematopoiesis Blood 1998 91 5 1479 1495 (Pubitemid 28110310)
44. Jenkins M., Hanley M. B., Moreno M. B., Wieder E., McCune J. M., Human immunodeficiency virus-1 infection interrupts thymopoiesis and multilineage hematopoiesis in vivo Blood 1998 91 8 2672 2678 (Pubitemid 28227515)
45. Alexaki A., Wigdahl B., HIV-1 infection of bone marrow hematopoietic progenitor cells and their role in trafficking and viral dissemination PLoS Pathogens 2008 4 12
46. Carter C. C., Onafuwa-Nuga A., McNamara L. A., Riddell J., Bixby D., Savona M. R., Collins K. L., HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs Nature Medicine 2010 16 4 446 451
47. Moir S., Ho J., Malaspina A., Wang W., DiPoto A. C., O'Shea M. A., Roby G., Kottilil S., Arthos J., Proschan M. A., Chun T. W., Fauci A. S., Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals Journal of Experimental Medicine 2008 205 8 1797 1805
48. Goodman J. W., Hodgson G. S., Evidence for stem cells in the peripheral blood of mice Blood 1962 19 702 714
49. Sauce D., Larsen M., Fastenackels S., Pauchard M., Ait-Mohand H., Schneider L., Guihot A., Boufassa F., Zaunders J., Iguertsira M., Bailey M., Gorochov G., Duvivier C., Carcelain G., Kelleher A. D., Simon A., Meyer L., Costagliola D., Deeks S. G., Lambotte O., Autran B., Hunt P. W., Katlama C., Appay V., HIV disease progression despite suppression of viral replication is associated with exhaustion of lymphopoiesis Blood 2011 117 19 5142 5151
50. Nielsen S. D., Afzelius P., Dam-Larsen S., Nielsen C., Nielsen J. O., Mathiesen L., Hansen J. E. S., Effect of granulocyte colony-stimulating factor (G-CSF) in human immunodeficiency virus-infected patients: increase in numbers of naive CD4 cells and CD34 cells makes G-CSF a candidate for use in gene therapy or to support antiretroviral therapy Journal of Infectious Diseases 1998 177 6 1733 1736 (Pubitemid 28243606)
51. Clark D. R., Ampel N. M., Hallett C. A., Yedavalli V. R. K., Ahmad N., DeLuca D., Peripheral blood from human immunodeficiency virus type 1-infected patients displays diminished T cell generation capacity Journal of Infectious Diseases 1997 176 3 649 654 (Pubitemid 27360529)
52. Park L. S., Friend D. J., Schmierer A. E., Dower S. K., Namen A. E., Murine interleukin 7 (IL-7) receptor. Characterization on an IL-7-dependent cell line Journal of Experimental Medicine 1990 171 4 1073 1089 (Pubitemid 20120134)
53. Schluns K. S., Kieper W. C., Jameson S. C., Lefranois L., Interleukin-7 mediates the homeostasis of nave and memory CD8 T cells in vivo Nature Immunology 2000 1 5 426 432
54. Llano A., Barretina J., Gutiérrez A., Blanco J., Cabrera C., Clotet B., Esté J. A., 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 Journal of Virology 2001 75 21 10319 10325 (Pubitemid 32948062)
55. Rethi B., Fluur C., Atlas A., Krzyzowska M., Mowafi F., Grtzmeier S., De Milito A., Bellocco R., Falk K. I., Rajnavlgyi., Chiodi F., Loss of IL-7R is associated with CD4 T-cell depletion, high interleukin-7 levels and CD28 down-regulation in HIV infected patients AIDS 2005 19 18 2077 2086 (Pubitemid 41668995)
56. Bellistri G. M., Casabianca A., Merlini E., Orlandi C., Ferrario G., Meroni L., Galli M., Magnani M., D'Arminio Monforte A., Marchetti G., Increased bone marrow interleukin-7 (IL-7)/IL-7R levels but reduced IL-7 responsiveness in HIV-positive patients lacking CD4 + gain on antiviral therapy PLoS ONE 2010 5 12, article e15663
57. Leone A., Picker L. J., Sodora D. L., IL-2, IL-7 and IL-15 as immuno-modulators during SIV/HIV vaccination and treatment Current HIV Research 2009 7 1 83 90
58. Ahmad A., Ahmad R., Iannello A., Toma E., Morisset R., Sindhu S. T. A. K., IL-15 and HIV infection: lessons for immunotherapy and vaccination Current HIV Research 2005 3 3 261 270 (Pubitemid 41052425)
59. Sirskyj D., Thze J., Kumar A., Kryworuchko M., Disruption of the c cytokine network in T cells during HIV infection Cytokine 2008 43 1 1 14
60. Hazenberg M. D., Otto S. A., van Benthem B. H. B., Roos M. T. L., Coutinho R. A., Lange J. M. A., Hamann D., Prins M., Miedema F., Persistent immune activation in HIV-1 infection is associated with progression to AIDS AIDS 2003 17 13 1881 1888 (Pubitemid 37070273)
61. Liu Z., Cumberland W. G., Hultin L. E., Kaplan A. H., Detels R., Giorgi J. V., CD8 + T-lymphocyte activation in HIV-1 disease reflects an aspect of pathogenesis distinct from viral burden and immunodeficiency Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 1998 18 4 332 340
62. Liu Z., Cumberland W. G., Hultin L. E., Prince H. E., Detels R., Giorgi J. V., Elevated CD38 antigen expression on CD8 + T cells Is a stronger marker for the risk of chronic HIV disease progression to AIDS and death in the multicenter AIDS Cohort study than CD4 + cell count, soluble immune activation markers, or combinations of HLA-DR and CD38 expression Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 1997 16 2 83 92
63. Liu Z., Hultin L. E., Cumberland W. G., Hultin P., Schmid I., Matud J. L., Detels R., Giorgi J. V., Elevated relative fluorescence intensity of CD38 antigen expression on CD8 + T cells is a marker of poor prognosis in HIV infection: results of 6 years of follow-up Communications in Clinical Cytometry 1996 26 1 1 7 (Pubitemid 26110007)
64. Giorgi J. V., Liu Z., Hultin L. E., Cumberland W. G., Hennessey K., Detels R., Elevated levels of CD38 + CD8 + T cells in HIV infection add to the prognostic value of low CD4 + T cell levels: results of 6 years of follow-up Journal of Acquired Immune Deficiency Syndromes 1993 6 8 904 912 (Pubitemid 23207458)
65. Weiss L., Haeffner-Cavaillon N., Laude M., Gilquin J., Kazatchkine M. D., HIV infection is associated with the spontaneous production of interleukin-1 (IL-1) in vivo and with an abnormal release of IL-1 in vitro AIDS 1989 3 11 695 699 (Pubitemid 20021428)
66. Molina J. M., Scadden D. T., Byrn R., Dinarello C. A., Groopman J. E., Production of tumor necrosis factor and interleukin 1 by monocytic cells infected with human immunodeficiency virus Journal of Clinical Investigation 1989 84 3 733 737 (Pubitemid 19228341)
67. Emilie D., Peuchmaur M., Maillot M. C., Crevon M. C., Brousse N., Delfraissy J. F., Dormont J., Galanaud P., Production of interleukins in human immunodeficiency virus-1-replicating lymph nodes Journal of Clinical Investigation 1990 86 1 148 159 (Pubitemid 20226987)
68. Birx D. L., Redfield R. R., Tencer K., Fowler A., Burke D. S., Tosato G., Induction of interleukin-6 during human immunodeficiency virus infection Blood 1990 76 11 2303 2310
69. Giorgi J. V., Hultin L. E., McKeating J. A., Johnson T. D., Owens B., Jacobson L. P., Shih R., Lewis J., Wiley D. J., Phair J. P., Wolinsky S. M., Detels R., Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage Journal of Infectious Diseases 1999 179 4 859 870 (Pubitemid 29159331)
70. Sousa A. E., Carneiro J., Meier-Schellersheim M., Grossman Z., Victorino R. M. M., CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load Journal of Immunology 2002 169 6 3400 3406 (Pubitemid 35013190)
71. Grossman Z., Meier-Schellersheim M., Sousa A. E., Victorino R. M. M., Paul W. E., CD4 + T-cell depletion in HIV infection: are we closer to understanding the cause? Nature Medicine 2002 8 4 319 323 (Pubitemid 34407019)
72. Owen R. E., Heitman J. W., Hirschkorn D. F., Lanteri M. C., Biswas H. H., Martin J. N., Krone M. R., Deeks S. G., Norris P. J., HIV+ elite controllers have low HIV-specific T-cell activation yet maintain strong, polyfunctional T-cell responses AIDS 2010 24 8 1095 1105
73. Broussard S. R., Staprans S. I., White R., Whitehead E. M., Feinberg M. B., Allan J. S., Simian immunodeficiency virus replicates to high levels in naturally infected African green monkeys without inducing immunologic or neurologic disease Journal of Virology 2001 75 5 2262 2275 (Pubitemid 32147565)
74. Kaur A., Grant R. M., Means R. E., Mcclure H., Feinberg M., Johnson R. P., Diverse host responses and outcomes following simian immunodeficiency virus SIVmac239 infection in sooty mangabeys and rhesus macaques Journal of Virology 1998 72 12 9597 9611 (Pubitemid 28520823)
75. Pesanti E. L., Effects of bacterial pneumonitis on development of pneumocystosis in rats American Review of Respiratory Disease 1982 125 6 723 726 (Pubitemid 12074589)
76. Hazenberg M. D., Hamann D., Schuitemaker H., Miedema F., T cell depletion in HIV-1 infection: how CD4 + T cells go out of stock Nature Immunology 2000 1 4 285 289
77. Benito J. M., Lpez M., Martn J. C., Lozano S., Martnez P., Gonzlez-Lahoz J., Soriano V., Differences in cellular activation and apoptosis in HIV-infected patients receiving protease inhibitors or nonnucleoside reverse transcriptase inhibitors AIDS Research and Human Retroviruses 2002 18 18 1379 1388 (Pubitemid 36044742)
78. Hunt P. W., Brenchley J., Sinclair E., McCune J. M., Roland M., Page-Shafer K., Hsue P., Emu B., Krone M., Lampiris H., Douek D., Martin J. N., Deeks S. G., Relationship between T cell activation and CD4 + T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy Journal of Infectious Diseases 2008 197 1 126 133 (Pubitemid 351263476)
79. Massanella M., Negredo E., Pérez-lvarez N., Puig J., Ruiz-Hernndez R., Bofill M., Clotet B., Blanco J., CD4 T-cell hyperactivation and susceptibility to cell death determine poor CD4 T-cell recovery during suppressive HAART AIDS 2010 24 7 959 968
80. Nakanjako D., Ssewanyana I., Mayanja-Kizza H., Kiragga A., Colebunders R., Manabe Y. C., Nabatanzi R., Kamya M. R., Cao H., 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 Infectious Diseases 2011 11, article 43
81. Benito J. M., Lpez M., Lozano S., Ballesteros C., Capa L., Martinez P., Gonzlez-Lahoz J., Soriano V., CD4 + T cell recovery beyond the first year of complete suppression of viral replication during highly active antiretroviral therapy is not influenced by CD8 + T cell activation Journal of Infectious Diseases 2005 192 12 2142 2146 (Pubitemid 41779214)
82. Gascon R. L., Narvez A. B., Zhang R., Kahn J. O., Hecht F. M., Herndier B. G., McGrath M. S., Increased HLA-DR expression on peripheral blood monocytes in subsets of subjects with primary HIV infection is associated with elevated CD4 T-cell apoptosis and CD4 T-cell depletion Journal of Acquired Immune Deficiency Syndromes 2002 30 2 146 153 (Pubitemid 34664410)
83. Mavigenr M., Delobel P., Cazabat M., Dubois M., L'Faqihi-Olive F. E., Raymond S., Pasquier C., Marchou B., Massip P., Izopet J., HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy PLoS ONE 2009 4 10
84. Delobel P., Flament S., Hamdane M., Mailliot C., Sambo A. V., Bégard S., Sergeant N., Delacourte A., Vilain J. P., Buée L., Abnormal Tau phosphorylation of the Alzheimer-type also occurs during mitosis Journal of Neurochemistry 2002 83 2 412 420 (Pubitemid 35191406)
85. Hazra R., Mackall C., Thymic function in HIV infection Current HIV/AIDS Reports 2005 2 1 24 28
86. Effros R. B., Pawelec G., Replicative senescence of T cells: does the Hayflick Limit lead to immune exhaustion? Immunology Today 1997 18 9 450 454 (Pubitemid 27381988)
87. Wolthers K. C., Wisman G. B. A., Otto S. A., De Roda Husman A. M., Schaft N., De Wolf F., Goudsmit J., Coutinho R. A., Van Der Zee A. G. J., Meyaard L., Miedema F., T cell telomere length in HIV-1 infection: no evidence for increased CD4 + T cell turnover Science 1996 274 5292 1543 1547 (Pubitemid 26403933)
88. Dagarag M., Ng H., Lubong R., Effros R. B., Yang O. O., Differential impairment of lytic and cytokine functions in senescent human immunodeficiency virus type 1-specific cytotoxic T lymphocytes Journal of Virology 2003 77 5 3077 3083 (Pubitemid 36228093)
89. Franzese O., Adamo R., Pollicita M., Comandini A., Laudisi A., Perno C. F., Aquaro S., Bonmassar E., Telomerase activity, hTERT expression, and phosphorylation are downregulated in CD4 + T lymphocytes infected with human immunodeficiency virus type 1 (HIV-1) Journal of Medical Virology 2007 79 5 639 646 (Pubitemid 46564364)
90. Meyaard L., Otto S. A., Jonker R. R., Mijnster M. J., Keet R. P. M., Miedema F., Programmed death of T cells in HIV-1 infection Science 1992 257 5067 217 219
91. Meyaard L., Otto S. A., Keet I. P. M., Roos M. T. L., Miedema F., Programmed death of T cells in human immunodeficiency virus infection. No correlation with progression to disease Journal of Clinical Investigation 1994 93 3 982 988
92. Bottarel F., Bonissoni S., Lucia M. B., Bragardo M., Bensi T., Buonfiglio D., Mezzatesta C., DiFranco D., Balotta C., Capobianchi M. R., Dianzani I., Cauda R., Dianzani U., Decreased function of Fas in patients displaying delayed progression of HIV-induced immune deficiency Hematology Journal 2001 2 4 220 227 (Pubitemid 32771595)
93. Gougeon M. L., Lecoeur H., Dulioust A., Enouf M. G., Crouvoisier M., Goujard C., Debord T., Montagnier L., Programmed cell death in peripheral lymphocytes from HIV-infected persons: increased susceptibility to apoptosis of CD4 and CD8 T cells correlates with lymphocyte activation and with disease progression Journal of Immunology 1996 156 9 3509 3520
94. Piconi S., Trabattoni D., Gori A., Parisotto S., Magni C., Meraviglia P., Bandera A., Capetti A., Rizzardini G., Clerici M., Immune activation, apoptosis, and treg activity are associated with persistently reduced CD4 + T-cell counts during antiretroviral therapy AIDS 2010 24 13 1991 2000
95. Keir M. E., Butte M. J., Freeman G. J., Sharpe A. H., PD-1 and its ligands in tolerance and immunity Annual Review of Immunology 2008 26 677 704 (Pubitemid 351600389)
96. Barber D. L., Wherry E. J., Masopust D., Zhu B., Allison J. P., Sharpe A. H., Freeman G. J., Ahmed R., Restoring function in exhausted CD8 T cells during chronic viral infection Nature 2006 439 7077 682 687 (Pubitemid 43237609)
97. Grabmeier-Pfistershammer K., Steinberger P., Rieger A., Leitner J., Kohrgruber N., Identification of PD-1 as a unique marker for failing immune reconstitution in HIV-1-infected patients on treatment Journal of Acquired Immune Deficiency Syndromes 2011 56 2 118 124
98. Appay V., Fastenackels S., Katlama C., Ait-Mohand H., Schneider L., Guihot A., Keller M., Grubeck-Loebenstein B., Simon A., Lambotte O., Hunt P. W., Deeks S. G., Costagliola D., Autran B., Sauce D., Old age and anti-cytomegalovirus immunity are associated with altered T-cell reconstitution in HIV-1-infected patients AIDS 2011 25 15 1813 1822
99. Steininger C., Puchhammer-Stckl E., Popow-Kraupp T., Cytomegalovirus disease in the era of highly active antiretroviral therapy (HAART) Journal of Clinical Virology 2006 37 1 1 9 (Pubitemid 44279524)
100. Read S., Mauze S., Asseman C., Bean A., Coffman R., Powrie F., CD38 + CD45RB(low) CD4 + T cells: a population of T cells with immune regulatory activities in vitro European Journal of Immunology 1998 28 11 3435 3447 (Pubitemid 28510754)
101. Baecher-Allan C., Brown J. A., Freeman G. J., Hafler D. A., CD4 + CD25high regulatory cells in human peripheral blood Journal of Immunology 2001 167 3 1245 1253 (Pubitemid 32703119)
102. Yoshizawa A., Ito A., Li Y., Koshiba T., Sakaguchi S., Wood K. J., Tanaka K., The roles of CD25 + CD4 + regulatory T cells in operational tolerance after living donor liver transplantation Transplantation Proceedings 2005 37 1 37 39 (Pubitemid 40459681)
103. Sakaguchi S., Naturally arising Foxp3-expressing CD25 + CD4 + regulatory T cells in immunological tolerance to self and non-self Nature Immunology 2005 6 4 345 352 (Pubitemid 41716771)
104. Oswald-Richter K., Grill S. M., Shariat N., Leelawong M., Sundrud M. S., Haas D. W., Unutmaz D., HIV infection of naturally occurring and genetically reprogrammed human regulatory T-cells PLoS Biology 2004 2 7
105. Tsunemi S., Iwasaki T., Imado T., Higasa S., Kakishita E., Shirasaka T., Sano H., Relationship of CD4 + CD25 + regulatory T cells to immune status in HIV-infected patients AIDS 2005 19 9 879 886 (Pubitemid 40834930)
106. Gaardbo J. C., Nielsen S. D., Vedel S. J., Ersbll A. K., Harritshj L., Ryder L. P., Nielsen J. O., Kolte L., 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 Clinical and Experimental Immunology 2008 154 1 80 86
107. Kolte L., Gaardbo J. C., Skogstrand K., Ryder L. P., Ersbll A. K., Nielsen S. D., Increased levels of regulatory T cells (Tregs) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive Tregs Clinical and Experimental Immunology 2009 155 1 44 52
108. Lim A., Tan D., Price P., Kamarulzaman A., Tan H. Y., James I., French M. A., 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 12 1525 1534 (Pubitemid 47075472)
109. Bernardes S. S., Borges I. K., Lima J. E., de Azevedo P., Conchon-Costa I., Felipe I., Saridakis H. O., Watanabe M. A. E., Involvement of regulatory T cells in HIV immunopathogenesis Current HIV Research 2010 8 4 340 346
110. Bettelli E., Carrier Y., Gao W., Korn T., Strom T. B., Oukka M., Weiner H. L., Kuchroo V. K., Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells Nature 2006 441 7090 235 238
111. Favre D., Lederer S., Kanwar B., Ma Z. M., Proll S., Kasakow Z., Mold J., Swainson L., Barbour J. D., Baskin C. R., Palermo R., Pandrea I., Miller C. J., Katze M. G., McCune J. M., Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection PLoS Pathogens 2009 5 2
112. Favre D., Mold J., Hunt P. W., Kanwar B., Loke P., Seu L., Barbour J. D., Lowe M. M., Jayawardene A., Aweeka F., Huang Y., Douek D. C., Brenchley J. M., Martin J. N., Hecht F. M., Deeks S. G., McCune J. M., Tryptophan catabolism by indoleamine 2, 3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease Science Translational Medicine 2010 2 32 32 36
113. Hunt P. W., Th17, gut, and HIV: therapeutic implications Current Opinion in HIV and AIDS 2010 5 2 189 193
114. Brandt L., Benfield T., Mens H., Clausen L. N., Katzenstein T. L., Fomsgaard A., Karlsson I., Low level of regulatory T cells and maintenance of balance between regulatory T cells and TH17 cells in HIV-1-infected elite controllers Journal of Acquired Immune Deficiency Syndromes 2011 57 2 101 108
115. Hartigan-O'Connor D. J., Hirao L. A., McCune J. M., Dandekar S., Th17 cells and regulatory T cells in elite control over HIV and SIV Current Opinion in HIV and AIDS 2011 6 3 221 227
116. Gaardbo J., Regulatory T cells (Tregs) are extremely prevalent in HIV infected individuals with immunological non-response, oral presentation PS12/2. European AIDS Clinical Society. In press
117. Mattapallil J. J., Douek D. C., Hill B., Nishimura Y., Martin M., Roederer M., Massive infection and loss of memory CD4 + T cells in multiple tissues during acute SIV infection Nature 2005 434 7037 1093 1097 (Pubitemid 40663481)
118. Guadalupe M., Reay E., Sankaran S., Prindiville T., Flamm J., McNeil A., Dandekar S., Severe CD4 + T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy Journal of Virology 2003 77 21 11708 11717 (Pubitemid 37271669)
119. Schacker T. W., Nguyen P. L., Beilman G. J., Wolinsky S., Larson M., Reilly C., Haase A. T., Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis Journal of Clinical Investigation 2002 110 8 1133 1139 (Pubitemid 35215894)
120. Schacker T. W., Reilly C., Beilman G. J., Taylor J., Skarda D., Krason D., Larson M., Haase A. T., Amount of lymphatic tissue fibrosis in HIV infection predicts magnitude of HAART-associated change in peripheral CD4 cell count AIDS 2005 19 18 2169 2171 (Pubitemid 41669008)
121. Finkel T. H., Tudor-Williams G., Banda N. K., Cotton M. F., Curiel T., Monks C., Baba T. W., Ruprecht R. M., Kupfer A., Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes Nature Medicine 1995 1 2 129 134
122. Finzi D., Hermankova M., Pierson T., Carruth L. M., Buck C., Chaisson R. E., Quinn T. C., Chadwick K., Margolick J., Brookmeyer R., Gallant J., Markowitz M., Ho D. D., Richman D. D., Siliciano R. F., Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy Science 1997 278 5341 1295 1300 (Pubitemid 27495742)
123. Cavert W., Notermans D. W., Staskus K., Wietgrefe S. W., Zupancic M., Gebhard K., Henry K., Zhang Z. Q., Mills R., McDade H., Goudsmit J., Danner S. A., Haase A. T., Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection Science 1997 276 5314 960 964 (Pubitemid 27209096)
124. Chun T. W., Nickle D. C., Justement J. S., Meyers J. H., Roby G., Hallahan C. W., Kottilil S., Moir S., Mican J. M., Mullins J. I., Ward D. J., Kovacs J. A., Mannon P. J., Fauci A. S., Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy Journal of Infectious Diseases 2008 197 5 714 720 (Pubitemid 351364472)
125. Chomont N., El-Far M., Ancuta P., Trautmann L., Procopio F. A., Yassine-Diab B., Boucher G., Boulassel M. R., Ghattas G., Brenchley J. M., Schacker T. W., Hill B. J., Douek D. C., Routy J. P., Haddad E. K., Sékaly R. P., HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation Nature Medicine 2009 15 8 893 900
126. Wang L., Robb C. W., Cloyd M. W., HIV induces homing of resting T lymphocytes to lymph nodes Virology 1997 228 2 141 152 (Pubitemid 27238780)
127. Wang L., Chen J. J. Y., Gelman B. B., Konig R., Cloyd M. W., A novel mechanism of CD4 lymphocyte depletion involves effects of HIV on resting lymphocytes: induction of lymph node homing and apoptosis upon secondary signaling through homing receptors Journal of Immunology 1999 162 1 268 276 (Pubitemid 29018929)
128. Cloyd M. W., Chen J. J. Y., Adeqboyega P., Wang L., How does HIV cause depletion of CD4 lymphocytes? A mechanism involving virus signaling through its cellular receptors Current Molecular Medicine 2001 1 5 545 550 (Pubitemid 33772034)
129. Epple H. J., Loddenkemper C., Kunkel D., Trger H., Maul J., Moos V., Berg E., Ullrich R., Schulzke J. D., Stein H., Duchmann R., Zeitz M., Schneider T., Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART Blood 2006 108 9 3072 3078
130. Bhaskaran K., Hamouda O., Sannes M., Boufassa F., Johnson A. M., Lambert P. C., Porter K., Changes in the risk of death after HIV seroconversion compared with mortality in the general population JAMA-Journal of the American Medical Association 2008 300 1 51 59 (Pubitemid 351920404)
131. Fedele F., Bruno N., Mancone M., Cardiovascular risk factors and HIV disease AIDS Reviews 2011 13 2 119 129
132. Grinspoon S. K., Metabolic syndrome and cardiovascular disease in patients with human immunodeficiency virus The American Journal of Medicine 2005 118, supplement 2 23S 28S
133. Deeks S. G., Antiretroviral treatment of HIV infected adults British Medical Journal 2006 332 7556 1489 1493 (Pubitemid 44365284)
134. Reynolds N. R., Cigarette smoking and HIV: more evidence for action AIDS Education and Prevention 2009 21 3 106 121
135. Van Tieu H., Koblin B. A., HIV, alcohol, and noninjection drug use Current Opinion in HIV and AIDS 2009 4 4 314 318
136. Adimora A. A., Auerbach J. D., Structural interventions for HIV prevention in the United States Journal of Acquired Immune Deficiency Syndromes 2010 55 2, supplement S132 S135
137. Greener R., Sarkar S., Risk and vulnerability: do socioeconomic factors influence the risk of acquiring HIV in Asia? AIDS 2010 24 3, supplement S3 S11
138. Lundgren J. D., Babiker A., El-Sadr W., Emery S., Grund B., Neaton J. D., Neuhaus J., Phillips A. N., Inferior clinical outcome of the CD4 + cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4 + cell counts and HIV RNA levels during follow-up Journal of Infectious Diseases 2008 197 8 1145 1155 (Pubitemid 351590050)
139. Gutiérrez F., Padilla S., Masi M., Iribarren J. A., Moreno S., Viciana P., Hernndez-Quero J., Alemn R., Vidal F., Salavert M., Blanco J. R., Leal M., Dronda F., Hoyos S. P., del Amo J., Berenguer J., Garca F., Labarga P., Muoz M. A., Arrizabalaga J., Aramburu M. J., Camino X., Rodrguez-Arrondo F., von Wichmann M. A., Pérez-Elas M. J., Casado Osorio J. L., Zamora A. M., Lopez-Cortés L. F., Gonzlez M. T., Alcaraz-Caballero R. M., Graca F., Muoz L., Parra J., Pea A., Hernndez Quero J., Gmez Sirvent J. L., Socas Ma. del M.A., Hernndez Calzadilla C., Lpez Lirola A. M., Peraire J., Viladés C., Veloso S., Richart C., Lacruz J., Falc Couchoud C., Blanes Jula M., Navarro Ibez V., Salavert Llet M., Bernal E., Ramos J. M., Escolano C., Ibarra V., Oteo J. A., Asensio R., Patients' characteristics and clinical implications of suboptimal CD4 T-cell gains after 1 year of successful antiretroviral therapy Current HIV Research 2008 6 2 100 107 (Pubitemid 351479789)
140. Phillips A. N., Gazzard B., Gilson R., Easterbrook P., Johnson M., Walsh J., Leen C., Fisher M., Orkin C., Anderson J., Pillay D., Delpech V., Sabin C., Schwenk A., Dunn D., Gompels M., Hill T., Porter K., Babiker A., Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naive individuals with high CD4 cell count AIDS 2007 21 13 1717 1721 (Pubitemid 47237558)
141. Obel N., Omland L. H., Kronborg G., Larsen C. S., Pedersen C., Pedersen G., Srensen H. T., Gerstoft J., Impact of Non-HIV and HIV risk factors on survival in HIV-Infected patients on haart: a population-based nationwide cohort study PLoS ONE 2011 6 7, article e22698
142. Smith C., Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D study: the data collection on adverse events of anti-HIV drugs (D:A:D) study group AIDS 2010 24 10 1537 1548
143. Waters L., Sabin C. A., Late HIV presentation: epidemiology, clinical implications and management Expert Review of Anti-Infective Therapy 2011 9 10 877 889
144. Mussini C., CD4 cell-monitored treatment interruption in patients with a CD4 cell count 500 106 cells/l AIDS 2005 19 3 287 294 (Pubitemid 40396560)
145. Lundgren J. D., Combination antiretroviral therapy and the risk of myocardial infarction: the data collection on adverse events of anti-HIV drugs (DAD) Study Group New England Journal of Medicine 2003 349 21 1993 2003 (Pubitemid 37448922)
146. Baker J. V., Henry W. K., Neaton J. D., The consequences of HIV infection and antiretroviral therapy use for cardiovascular disease risk: shifting paradigms Current Opinion in HIV and AIDS 2009 4 3 176 182
147. Friis-Mller N., Reiss P., Sabin C. A., Weber R., Monforte A. D. A., El-Sadr W., Thiébaut R., De Wit S., Kirk O., Fontas E., Law M. G., Phillips A., Lundgren J. D., Class of antiretroviral drugs and the risk of myocardial infarction New England Journal of Medicine 2007 356 17 1723 1735 (Pubitemid 46658704)
148. Phillips A. N., Neaton J., Lundgren J. D., The role of HIV in serious diseases other than AIDS AIDS 2008 22 18 2409 2418
149. Kaplan R. C., Kingsley L. A., Gange S. J., Benning L., Jacobson L. P., Lazar J., Anastos K., Tien P. C., Sharrett A. R., Hodis H. N., Low CD4 + T-cell count as a major atherosclerosis risk factor in HIV-infected women and men AIDS 2008 22 13 1615 1624
150. Jaffe H. W., De Stavola B. L., Carpenter L. M., Porter K., Cox D. R., Immune reconstitution and risk of Kaposi sarcoma and non-Hodgkin lymphoma in HIV-infected adults AIDS 2011 25 11 1395 1403
151. Bohlius J., Schmidlin K., Costagliola D., Fatkenheuer G., May M., Caro-Murillo A. M., Incidence and risk factors of HIV-related non-Hodgkin's lymphoma in the era of combination antiretroviral therapy: a European multicohort study Antiviral Therapy 2009 14 8 1065 1074
152. Zanet E., Berretta M., Martellotta F., Cacopardo B., Fisichella R., Tavio M., Berretta S., Tirelli U., Anal cancer: focus on HIV-positive patients in the HAART era Current HIV Research 2011 9 2 70 81
153. Monforte A. D., Abrams D., Pradier C., Weber R., Reiss P., Bonnet F., Kirk O., Law M., De Wit S., Friis-Mller N., Phillips A. N., Sabin C. A., Lundgren J. D., Collins S., Loeliger E., Tressler R., Weiler I., Friis-Mller N., Worm S. W., Sabin C. A., Sjl A., Lundgren J. D., Sawitz A., Rickenbach M., Pezzotti P., Krum E., Gras L., Balestre E., Sundstrm A., Poll B., Fontas E., Torres F., Petoumenos K., Kjr J., HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies AIDS 2008 22 16 2143 2153
154. Reekie J., Kosa C., Engsig F., Monforte A. D., Wiercinska-Drapalo A., Domingo P., Antunes F., Clumeck N., Kirk O., Lundgren J. D., Mocroft A., Relationship between current level of immunodeficiency and non-acquired immunodeficiency syndrome-defining malignancies Cancer 2010 116 22 5306 5315
155. Heaton R. K., Clifford D. B., Franklin D. R., Woods S. P., Ake C., Vaida F., Ellis R. J., Letendre S. L., Marcotte T. D., Atkinson J. H., Rivera-Mindt M., Vigil O. R., Taylor M. J., Collier A. C., Marra C. M., Gelman B. B., McArthur J. C., Morgello S., Simpson D. M., McCutchan J. A., Abramson I., Gamst A., Fennema-Notestine C., Jernigan T. L., Wong J., Grant I., HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: charter Study Neurology 2010 75 23 2087 2096
156. Ellis R. J., Badiee J., Vaida F., Letendre S., Heaton R. K., Clifford D., Collier A. C., Gelman B., McArthur J., Morgello S., McCutchan J. A., Grant I., CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy AIDS 2011 25 14 1747 1751
157. Bartlett J. A., Fath M. J., DeMasi R., Hermes A., Quinn J., Mondou E., Rousseau F., An updated systematic overview of triple combination therapy in antiretroviral-naive HIV-infected adults AIDS 2006 20 16 2051 2064 (Pubitemid 44611058)
158. Gulick R. M., Lalezari J., Goodrich J., Clumeck N., Dejesus E., Horban A., Nadler J., Clotet B., Karlsson A., Wohlfeiler M., Montana J. B., McHale M., Sullivan J., Ridgway C., Felstead S., Dunne M. W., Van Der Ryst E., Mayer H., Maraviroc for previously treated patients with R5 HIV-1 infection New England Journal of Medicine 2008 359 14 1429 1441
159. Wilkin T., Maraviroc intensification for suboptimal CD4 + cell response despite sustained virologic suppression: ACTG 5256 Proceedings of the 17th Conference on Retrovirus and Opportunistic Infections (CROI '10) 2010 abstract 285
160. Wilkin T. J., Ribaudo H. R., Tenorio A. R., Gulick R. M., The relationship of CCR5 antagonists to CD4 + T-cell gain: a meta-regression of recent clinical trials in treatment-experienced HIV-infected patients HIV Clinical Trials 2010 11 6 351 358
161. Steigbigel R. T., Cooper D. A., Teppler H., Eron J. J., Gatell J. M., Kumar P. N., Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials Clinical Infectious Diseases 2010 50 4 605 612
162. Hatano H., Hayes T. L., Dahl V., Sinclair E., Lee T.-H., Hoh R., Lampiris H., Hunt P. W., Palmer S., McCune J. M., Martin J. N., Busch M. P., Shacklett B. L., Deeks S. G., A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4 + T cell response Journal of Infectious Diseases 2011 203 7 960 968
163. Byakwaga H., Kelly M., Purcell D. F.J., French M. A., Amin J., Lewin S. R., Haskelberg H., Kelleher A. D., Garsia R., Boyd M. A., Cooper D. A., Emery S., Intensification of antiretroviral therapy with raltegravir or addition of hyperimmune bovine colostrum in HIV-infected patients with suboptimal CD4 + T-cell response: a randomized controlled trial Journal of Infectious Diseases 2011 204 10 1532 1540
164. Molina J.-M., LaMarca A., Andrade-Villanueva J., Clotet B., Clumeck N., Liu Y.-P., Zhong L., Margot N., Cheng A. K., Chuck S. L., Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study The Lancet Infectious Diseases 2012 12 1 27 35
165. Lalezari J. P., Henry K., O'Hearn M., Montaner J. S. G., Piliero P. J., Trottier B., Walmsley S., Cohen C., Kuritzkes D. R., Eron J. J., Chung J., DeMasi R., Donatacci L., Drobnes C., Delehanty J., Salgo M., Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America New England Journal of Medicine 2003 348 22 2175 2185 (Pubitemid 36618128)
166. Lazzarin A., Clotet B., Cooper D., Reynes J., Arastéh K., Nelson M., Katlama C., Stellbrink H. J., Delfraissy J. F., Lange J., Huson L., DeMasi R., Wat C., Delehanty J., Drobnes C., Salgo M., Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia New England Journal of Medicine 2003 348 22 2186 2195 (Pubitemid 36618129)
167. Joly V., Intensification of HAART through the addition of enfuvirtide in naive HIV-infected patients with severe immunosuppression does not improve immunological response: results of a prospective randomised multicenter trial Proceedings of the 17th Conference on Retrovirus and Opportunistic Infections (CROI '10) 2010 abstract 282
168. Pett S. L., Kelleher A. D., Emery S., Role of interleukin-2 in patients with HIV infection Drugs 2010 70 9 1115 1130
169. Carcelain G., Saint-Mézard P., Altes H. K., Tubiana R., Grenot P., Rabian C., De Boer R., Costagliola D., Katlama C., Debré P., Autran B., IL-2 therapy and thymic production of naive CD4 T cells in HIV-infected patients with severe CD4 lymphopenia AIDS 2003 17 6 841 850 (Pubitemid 36547656)
170. Sabbatini F., Bandera A., Ferrario G., Trabattoni D., Marchetti G., Franzetti F., Clerici M., Gori A., Qualitative immune modulation by interleukin-2 (IL-2) adjuvant therapy in immunological non responder HIV-infected patients PLoS ONE 2010 5 11
171. Marchetti G., Meroni L., Varchetta S., Terzieva V., Bandera A., Manganaro D., Molteni C., Trabattoni D., Fossati S., Clerici M., Galli M., Moroni M., Franzetti F., Gori A., Low-dose prolonged intermittent interleukin-2 adjuvant therapy: results of a randomized trial among human immunodeficiency virus-positive patients with advanced immune impairment Journal of Infectious Diseases 2002 186 5 606 616 (Pubitemid 34925532)
172. MacKall C. L., Fry T. J., Gress R. E., Harnessing the biology of IL-7 for therapeutic application Nature Reviews Immunology 2011 11 5 330 342
173. Leone A., Rohankhedkar M., Okoye A., Legasse A., Axthelm M. K., Villinger F., Piatak M., Lifson J. D., Assouline B., Morre M., Picker L. J., Sodora D. L., Increased CD4 + T cell levels during IL-7 administration of antiretroviral therapy-treated simian immunodeficiency virus-positive macaques are not dependent on strong proliferative responses Journal of Immunology 2010 185 3 1650 1659
174. Sereti I., Dunham R. M., Spritzler J., Aga E., Proschan M. A., Medvik K., Battaglia C. A., Landay A. L., Pahwa S., Fischl M. A., Asmuth D. M., Tenorio A. R., Altman J. D., Fox L., Moir S., Malaspina A., Morre M., Buffet R., Silvestri G., Lederman M. M., IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection Blood 2009 113 25 6304 6314
175. Levy Y., Lacabaratz C., Weiss L., Viard J.-P., Goujard C., Lelivre J.-D., Boué F., Molina J.-M., Rouzioux C., Avettand-Fénol V., Croughs T., Beq S., Thiébaut R., Chne G., Morre M., Delfraissy J.-F., Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment Journal of Clinical Investigation 2009 119 4 997 1007
176. Sports C., Hakim F. T., Memon S. A., Zhang H., Chua K. S., Brown M. R., Fleisher T. A., Krumlauf M. C., Babb R. R., Chow C. K., Fry T. J., Engels J., Buffet R., Morre M., Amato R. J., Venzon D. J., Korngold R., Pecora A., Gress R. E., Mackall C. L., Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets Journal of Experimental Medicine 2008 205 7 1701 1714 (Pubitemid 351962032)
177. Rosenberg S. A., Sports C., Ahmadzadeh M., Fry T. J., Ngo L. T., Schwarz S. L., Stetler-Stevenson M., Morton K. E., Mavroukakis S. A., Morre M., Buffet R., Mackall C. L., Gress R. E., IL-7 administration to humans leads to expansion of CD8 + and CD4 + cells but a relative decrease of CD4 + T-regulatory cells Journal of Immunotherapy 2006 29 3 313 319 (Pubitemid 44297299)
178. Okamoto Y., Douek D. C., McFarland R. D., Koup R. A., Effects of exogenous interleukin-7 on human thymus function Blood 2002 99 8 2851 2858 (Pubitemid 34525374)
179. Sereti I., Recombinant IL-7 expands CD4 T cells in peripheral blood and gut mucosa of chronically HIV-infected immunological non-responder patients Proceedings of the 18th Conference on Retrovirus and Opportunistic Infections (CROI '10) 2011 abstract 376
180. Lugli E., Mueller Y. M., Lewis M. G., Villinger F., Katsikis P. D., Roederer M., IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques Blood 2011 118 9 2520 2529
181. Mueller Y. M., Petrovas C., Bojczuk P. M., Dimitriou I. D., Beer B., Silvera P., Villinger F., Cairns J. S., Gracely E. J., Lewis M. G., Katsikis P. D., Interleukin-15 increases effector memory CD8 + T cells and NK cells in simian immunodeficiency virus-infected macaques Journal of Virology 2005 79 8 4877 4885 (Pubitemid 40464238)
182. Picker L. J., Reed-Inderbitzin E. F., Hagen S. I., Edgar J. B., Hansen S. G., Legasse A., Planer S., Piatak M., Lifson J. D., Maino V. C., Axthelm M. K., Villinger F., IL-15 induces CD4 + effector memory T cell production and tissue emigration in nonhuman primates Journal of Clinical Investigation 2006 116 6 1514 1524
183. Mueller Y. M., Do D. H., Altork S. R., Artlett C. M., Gracely E. J., Katsetos C. D., Legido A., Villinger F., Altman J. D., Brown C. R., Lewis M. G., Katsikis P. D., IL-15 treatment during acute Simian Immunodeficiency Virus (SIV) infection increases viral set point and accelerates disease progression despite the induction of stronger SIV-specific CD8 + T cell responses Journal of Immunology 2008 180 1 350 360
184. Benedini S., Terruzzi I., Lazzarin A., Luzi L., Recombinant human growth hormone: rationale for use in the treatment of HIV-associated lipodystrophy BioDrugs 2008 22 2 101 112 (Pubitemid 351419122)
185. Gelato M., McNurlan M., Freedland E., Role of recombinant human growth hormone in HIV-associated wasting and cachexia: pathophysiology and rationale for treatment Clinical Therapeutics 2007 29 11 2269 2288 (Pubitemid 350298124)
186. Smith K., Zheng L., Bosch R., Margolis D. M., Tenorio A., Napolitano L., Saag M., Connick E., Gross B., Francis I., Valdez H., Muurahainen N., Stocker V., Pollard R., Treatment with recombinant growth hormone is associated with modest improvement in CD4 lymphocyte reconstitution in HIV-infected persons on antiretroviral therapy: results of ACTG A5174 AIDS Research and Human Retroviruses 2010 26 4 425 432
187. Napolitano L. A., Schmidt D., Gotway M. B., Ameli N., Filbert E. L., Ng M. M., Clor J. L., Epling L., Sinclair E., Baum P. D., Li K., Killian M. L., Bacchetti P., McCune J. M., Growth hormone enhances thymic function in HIV-1-infected adults Journal of Clinical Investigation 2008 118 3 1085 1098 (Pubitemid 351364616)
188. Napolitano L. A., Lo J. C., Gotway M. B., Mulligan K., Barbour J. D., Schmidt D., Grant R. M., Halvorsen R. A., Schambelan M., McCune J. M., Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults treated with growth hormone AIDS 2002 16 8 1103 1111 (Pubitemid 34533848)
189. Hansen B. R., Kolte L., Haugaard S. B., Dirksen C., Jensen F. K., Ryder L. P., Srensen A. L., Flyvbjerg A., Nielsen S. D., Andersen O., Improved thymic index, density and output in HIV-infected patients following low-dose growth hormone therapy: a placebo controlled study AIDS 2009 23 16 2123 2131
190. Andersen O., Hansen B. R., Troensegaard W., Flyvbjerg A., Madsbad S., rskov H., Nielsen J. O., Iversen J., Haugaard S. B., Sustained low-dose growth hormone therapy optimizes bioactive insulin-like growth factor-I level and may enhance CD4 T-cell number in HIV infection Journal of Medical Virology 2010 82 2 197 205
191. Sivakumar T., Mechanic O. J., Fehmie D. A., Paul B. T., Growth hormone axis treatments for HIV-associated lipodystrophy: a systematic review of placebo-controlled trials HIV Medicine 2011 12 8 453 462
192. Dhillon S., Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy Drugs 2011 71 8 1071 1091
193. Wang Y., Chen G., Qiao S., Ma X., Tang X., Sun A., Wu D., Keratinocyte growth factor enhanced immune reconstitution in murine allogeneic umbilical cord blood cell transplant Leukemia and Lymphoma 2011 52 8 1556 1566
194. Min D., Panoskaltsis-Mortari A., Kuro-o M., Hollnder G. A., Blazar B. R., Weinberg K. I., Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging Blood 2007 109 6 2529 2537 (Pubitemid 46425898)
195. Seggewiss R., Loré K., Guenaga F. J., Pittaluga S., Mattapallil J., Chow C. K., Koup R. A., Camphausen K., Nason M. C., Meier-Schellersheim M., Donahue R. E., Blazar B. R., Dunbar C. E., Douek D. C., Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques Blood 2007 110 1 441 449 (Pubitemid 47026867)
196. Rizwan R., Levine J. E., Defor T., Ferarra J. L., Weisdorf D. J., Blazar B. R., Verneris M. R., Peritransplant palifermin use and lymphocyte recovery after T-cell replete, matched related allogeneic hematopoietic cell transplantation American Journal of Hematology 2011 86 10 879 882
197. Blazar B. R., Weisdorf D. J., DeFor T., Goldman A., Braun T., Silver S., Ferrara J. L. M., Phase 1/2 randomized, placebo-control trial of palifermin to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) Blood 2006 108 9 3216 3222
198. Vassilopoulos D., Calabrese L. H., Risks of immunosuppressive therapies including biologic agents in patients with rheumatic diseases and co-existing chronic viral infections Current Opinion in Rheumatology 2007 19 6 619 625 (Pubitemid 47530884)
199. Plaeger S. F., Collins B. S., Musib R., Deeks S. G., Read S., Embry A., Immune activation in the pathogenesis of treated chronic HIV disease: a workshop summary AIDS Research and Human Retroviruses. In press
200. Vermeulen J. N., Prins J. M., Bunnik E., Hack C. E., Jurriaans S., Miedema F., Lange J. M. A., Schuitemaker H., Intravenous immunoglobulin (IVIG) treatment for modulation of immune activation in human immunodeficiency virus type 1 infected therapy-naive individuals AIDS Research and Human Retroviruses 2007 23 11 1348 1353
201. Lindkvist A., Edén A., Norstrm M. M., Gonzalez V. D., Nilsson S., Svennerholm B., Karlsson A. C., Sandberg J. K., Snnerborg A., Gisslén M., Reduction of the HIV-1 reservoir in resting CD4 + T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study AIDS Research and Therapy 2009 6, article 15
202. Mellberg T., Gonzalez V. D., Lindkvist A., Edén A., Snnerborg A., Sandberg J. K., Svennerholm B., Gisslén M., Rebound of residual plasma viremia after initial decrease following addition of intravenous immunoglobulin to effective antiretroviral treatment of HIV AIDS Research and Therapy 2011 8, article 21
203. Gonzalez V. D., Falconer K., Blom K. G., Reichard O., Mrn B., Laursen A. L., Weis N., Alaeus A., Sandberg J. K., High levels of chronic immune activation in the T-cell compartments of patients coinfected with hepatitis C virus and human immunodeficiency virus type 1 and on highly active antiretroviral therapy are reverted by alpha interferon and ribavirin treatment Journal of Virology 2009 83 21 11407 11411
204. Hunt P. W., Martin J. N., Sinclair E., Epling L., Teague J., Jacobson M. A., Tracy R. P., Corey L., Deeks S. G., Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD41 + T cell recovery on antiretroviral therapy Journal of Infectious Diseases 2011 203 10 1474 1483
205. Hunt P. W., Th17, gut, and HIV: therapeutic implications Current Opinion in HIV and AIDS 2010 5 2 189 193
206. Merlini E., Bai F., Bellistr G. M., Tincati C., d'Arminio Monforte A., Marchetti G., Evidence for polymicrobic flora translocating in peripheral blood of HIV-infected patients with poor immune response to antiretroviral therapy PLoS ONE 2011 6 4, article e18580
207. Brenchley J. M., Price D. A., Schacker T. W., Asher T. E., Silvestri G., Rao S., Kazzaz Z., Bornstein E., Lambotte O., Altmann D., Blazar B. R., Rodriguez B., Teixeira-Johnson L., Landay A., Martin J. N., Hecht F. M., Picker L. J., Lederman M. M., Deeks S. G., Douek D. C., Microbial translocation is a cause of systemic immune activation in chronic HIV infection Nature Medicine 2006 12 12 1365 1371 (Pubitemid 44924494)
208. Jiang W., Lederman M. M., Hunt P., Sieg C. F., Haley K., Rodriguez B., Landay A., Martin J., Sinclair E., Asher A. I., Deeks S. G., Douek D. C., Brenchley J. M., Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection Journal of Infectious Diseases 2009 199 8 1177 1185
209. Marchetti G., Bellistr G. M., Borghi E., Tincati C., Ferramosca S., La Francesca M., Morace G., Gori A., Monforte A. D., Microbial translocation is associated with sustained failure in CD4 + T-cell reconstitution in HIV-infected patients on long-term highly active antiretroviral therapy AIDS 2008 22 15 2035 2044
210. Hummelen R., Changalucha J., Butamanya N. L., Koyama T. E., Cook A., Habbema J. D., Reid G., Effect of 25 weeks probiotic supplementation on immune function of HIV patients Gut Microbes 2011 2 2 80 85
211. Pettersen F. O., Torheim E. A., Dahm A. E., Aaberge I. S., Lind A., Holm M., Aandahl E. M., Sandset P. M., Taskén K., Kvale D., An exploratory trial of cyclooxygenase type 2 inhibitor in HIV-1 infection: downregulated immune activation and improved T cell-dependent vaccine responses Journal of Virology 2011 85 13 6557 6566
212. Kvale D., Ormaasen V., Kran A. M. B., Johansson C. C., Aukrust P., Aandahl E. M., Frland S. S., Taskén K., Immune modulatory effects of cyclooxygenase type 2 inhibitors in HIV patients on combination antiretroviral treatment AIDS 2006 20 6 813 820 (Pubitemid 43731562)
213. Johansson C. C., Bryn T., Aandahl E. M., Areklett M. A., Aukrust P., Taskén K., Frland S. S., Treatment with type-2 selective and non-selective cyclooxygenase inhibitors improves T-cell proliferation in HIV-infected patients on highly active antiretroviral therapy AIDS 2004 18 6 951 952 (Pubitemid 38553718)