Replication capacity in relation to immunologic and virologic outcomes in HIV-1-infected treatment-naive subjects

Journal of Acquired Immune Deficiency Syndromes

Volumn 50, Issue 3, 2009, Pages 250-258

  Skowron, Gail ^a,g   Spritzler, John G ^b   Weidler, Jodi ^c   Robbins, Gregory K ^d   Johnson, Victoria A ^e   Chan, Ellen S ^b   Asmuth, David M ^f   Gandhi, Rajesh T ^d   Lie, Yolanda ^c   Bates, Michael ^c   Pollard, Richard B ^f  

^a MIRIAM HOSPITAL   (United States)

^b HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^c MONOGRAM BIOSCIENCES   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

^e UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g ROGER WILLIAMS MEDICAL CENTER   (United States)

Author keywords

Activation; HIV; Immune reconstitution; Memory; Pathogenesis; Replication capacity; Viral fitness

Indexed keywords

DIDANOSINE; EFAVIRENZ; LAMIVUDINE; NELFINAVIR; STAVUDINE; VIRUS RNA; ZIDOVUDINE;

ADOLESCENT; ADULT; AGED; ANTIVIRAL THERAPY; ARTICLE; ASSAY; CD4 LYMPHOCYTE COUNT; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; EMBRYO; FEMALE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; MAJOR CLINICAL STUDY; MALE; MEMORY CELL; MULTIVARIATE ANALYSIS; OUTCOME ASSESSMENT; PRIORITY JOURNAL; T LYMPHOCYTE ACTIVATION; TREATMENT DURATION; UNIVARIATE ANALYSIS; VIRUS REPLICATION; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MIDDLE AGED; PHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL; VIROLOGY; VIRUS LOAD;

ADULT; AGED; CD4 LYMPHOCYTE COUNT; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; MALE; MIDDLE AGED; VIRAL LOAD; VIRUS REPLICATION;

EID: 63149138413     PISSN: 15254135     EISSN: None     Source Type: Journal    
DOI: 10.1097/QAI.0b013e3181938faf     Document Type: Article

References (84)

1. Gandhi RT, Spritzler J, Chan E, et al. Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384. J Acquir Immune Defic Syndr. 2006;42:426-434.
2. Wolbers M, Battegay M, Hirschel B, et al. CD4+ T-cell count increase in HIV-1-infected patients with suppressed viral load within 1 year after start of antiretroviral therapy. Antivir Ther. 2007;12:889-897.
3. Landay A, da Silva BA, King MS, et al. Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir-ritonavir treatment. Clin Infect Dis. 2007;44:749-754.
4. Kaufmann GR, Perrin L, Pantaleo G, et al. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med. 2003; 163:2187-2195.
5. Hunt PW, Deeks SG, Rodriguez B, et al. Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy. AIDS. 2003;17:1907-1915.
6. Kaufmann GR, Furrer H, Ledergerber B, et al. Characteristics, determinants, and clinical relevance of CD4 T cell recovery to <500 cells/microL in HIV type 1-infected individuals receiving potent antiretroviral therapy. Clin Infect Dis. 2005;41:361-372.
7. Moore RD, Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis. 2007;44:441-446.
8. Mildvan D, Bosch RJ, Kim RS, et al. Immunophenotypic markers and antiretroviral therapy (IMART): T cell activation and maturation help predict treatment response. J Infect Dis. 2004;189:1811-1820.
9. Goicoechea M, Smith DM, Liu L, et al. Determinants of CD4+ T cell recovery during suppressive antiretroviral therapy: association of immune activation, T cell maturation markers, and cellular HIV-1 DNA. J Infect Dis. 2006;194:29-37.
10. Fernandez S, Price P, McKinnon EJ, et al. Low CD4+ T-cell counts in HIV patients receiving effective antiretroviral therapy are associated with CD4+ T-cell activation and senescence but not with lower effector memory T-cell function. Clin Immunol. 2006;120:163-170.
11. Hunt PW, Martin JN, Sinclair E, et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003;187:1534-1543.
12. Anthony KB, Yoder C, Metcalf JA, et al. Incomplete CD4 T cell recovery in HIV-1 infection after 12 months of highly active antiretroviral therapy is associated with ongoing increased CD4 T cell activation and turnover. J Acquir Immune Defic Syndr. 2003;33:125-133.
13. Deeks SG, Wrin T, Liegler T, et al. Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med. 2001;344: 472-480.
14. Daar ES, Kesler KL, Wrin T, et al. HIV-1 pol replication capacity predicts disease progression. AIDS. 2005;19:871-877.
15. Barbour JD, Hecht FM, Wrin T, et al. Higher CD4+ T cell counts associated with low viral pol replication capacity among treatment-naive adults in early HIV-1 infection. J Infect Dis. 2004;190:251-256.
16. Barbour JD, Hecht FM, Little SJ, et al. Greater CD4 T-cell gains after one year of antiretroviral therapy are associated with lower HIV-1 pol replication capacity. AIDS. 2006;20:2123-2125.
17. Hicks C, Eron J, Keiser P, et al. HIV-1 replication capacity as an independent predictor of pre-treatment CD4 lymphocyte count. Presented at: 12th Conference on Retroviruses and Opportunistic Infections; 2005; Boston, MA. Abstract 345.
18. De Luca A, Weidler J, Di Giambenedetto S, et al. Association of HIV-1 replication capacity with treatment outcomes in patients with virologic treatment failure. J Acquir Immune Defic Syndr. 2007;45:411-417.
19. Haubrich R, Wrin T, Hellmann N, et al, and the CCTG. Replication Capacity (RC) as a Predictor of Immunologic and Virologic Benefit Despite Virologic Failure of an Antiretroviral Regimen. Antivir Ther. 2002;7:S101.
20. Shafer RW, Smeaton LM, Robbins GK, et al. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003;349:2304-2315.
21. Robbins GK, De Gruttola V, Shafer RW, et al. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003;349:2293-2303.
22. Petropoulos CJ, Parkin NT, Limoli KL, et al. A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2000;44:920-928.
23. Campbell TB, Schneider K, Wrin T, et al. Relationship between in vitro human immunodeficiency virus type 1 replication rate and virus load in plasma. J Virol. 2003;77:12105-12112.
24. Moore DM, Hogg RS, Yip B, et al. Discordant immunologic and virologic responses to highly active antiretroviral therapy are associated with increased mortality and poor adherence to therapy. J Acquir Immune Defic Syndr. 2005;40:288-293.
25. Schechter M, Tuboi SH. Discordant immunological and virological responses to antiretroviral therapy. J Antimicrob Chemother. 2006;58: 506-510.
26. Carbone J, Gil J, Benito JM, et al. Increased levels of activated subsets of CD4 T cells add to the prognostic value of low CD4 T cell counts in a cohort of HIV-infected drug users. AIDS. 2000;14:2823-2829.
27. Leng Q, Borkow G, Weisman Z, et al. Immune activation correlates better than HIV plasma viral load with CD4 T-cell decline during HIV infection. J Acquir Immune Defic Syndr. 2001;27:389-397.
28. Hazenberg MD, Otto SA, van Benthem BH, et al. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS. 2003;17:1881-1888.
29. Choudhary SK, Vrisekoop N, Jansen CA, et al. Low immune activation despite high levels of pathogenic human immunodeficiency virus type 1 results in long-term asymptomatic disease. J Virol. 2007;81: 8838-8842.
30. Sousa AE, Carneiro J, Meier-Schellersheim M, et al. 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. J Immunol. 2002;169: 3400-3406.
31. Deeks SG, Hoh R, Grant RM, et al. CD4+ T cell kinetics and activation in human immunodeficiency virus-infected patients who remain viremic despite long-term treatment with protease inhibitor-based therapy. J Infect Dis. 2002;185:315-323.
32. Silvestri G, Sodora DL, Koup RA, et al. Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity. 2003;18:441-452.
33. Broussard SR, Staprans SI, White R, et al. Simian immunodeficiency virus replicates to high levels in naturally infected African green monkeys without inducing immunologic or neurologic disease. J Virol. 2001;75: 2262-2275.
34. Mehandru S, Poles MA, Tenner-Racz K, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 2004;200:761-770.
35. Brenchley JM, Schacker TW, Ruff LE, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med. 2004;200:749-759.
36. Hazenberg MD, Hamann D, Schuitemaker H, et al. T cell depletion in HIV-1 infection: how CD4+ T cells go out of stock. Nat Immunol. 2000; 1: 285-289.
37. Pakker NG, Notermans DW, de Boer RJ, et al. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat Med. 1998; 4:208-214.
38. +lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues. J Clin Invest. 1999;103:1391-1398.
39. Lederman MM, Connick E, Landay A, et al. Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315. J Infect Dis. 1998;178:70-79.
40. Montaner J, Lederman M, Hill A, et al. Discordant CD4/RNA responses to HAARTare strongly associated with high-baseline CD4 count and low HIVRNA: analysis of 406 naive patients. Presented at: Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy; San Francisco, CA, September 26-29, 1999. Abstract 1993.
41. Lederman MM, Valdez H. Immune restoration with antiretroviral therapies: implications for clinical management. JAMA. 2000;284:223-228.
42. Daar ES, Kesler KL, Petropoulos CJ, et al. Baseline HIV type 1 coreceptor tropism predicts disease progression. Clin Infect Dis. 2007;45:643-649.
43. Gandhi RT, Spritzler J, Chan E, et al. Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384. J Acquir Immune Defic Syndr. 2006;42:426-434.
44. Wolbers M, Battegay M, Hirschel B, et al. CD4+ T-cell count increase in HIV-1-infected patients with suppressed viral load within 1 year after start of antiretroviral therapy. Antivir Ther. 2007;12:889-897.
45. Landay A, da Silva BA, King MS, et al. Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir-ritonavir treatment. Clin Infect Dis. 2007;44:749-754.
46. Kaufmann GR, Perrin L, Pantaleo G, et al. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med. 2003; 163:2187-2195.
47. Hunt PW, Deeks SG, Rodriguez B, et al. Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy. AIDS. 2003;17:1907-1915.
48. Kaufmann GR, Furrer H, Ledergerber B, et al. Characteristics, determinants, and clinical relevance of CD4 T cell recovery to <500 cells/microL in HIV type 1-infected individuals receiving potent antiretroviral therapy. Clin Infect Dis. 2005;41:361-372.
49. Moore RD, Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis. 2007;44:441-446.
50. Mildvan D, Bosch RJ, Kim RS, et al. Immunophenotypic markers and antiretroviral therapy (IMART): T cell activation and maturation help predict treatment response. J Infect Dis. 2004;189:1811-1820.
51. Goicoechea M, Smith DM, Liu L, et al. Determinants of CD4+ T cell recovery during suppressive antiretroviral therapy: association of immune activation, T cell maturation markers, and cellular HIV-1 DNA. J Infect Dis. 2006;194:29-37.
52. Fernandez S, Price P, McKinnon EJ, et al. Low CD4+ T-cell counts in HIV patients receiving effective antiretroviral therapy are associated with CD4+ T-cell activation and senescence but not with lower effector memory T-cell function. Clin Immunol. 2006;120:163-170.
53. Hunt PW, Martin JN, Sinclair E, et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003;187:1534-1543.
54. Anthony KB, Yoder C, Metcalf JA, et al. Incomplete CD4 T cell recovery in HIV-1 infection after 12 months of highly active antiretroviral therapy is associated with ongoing increased CD4 T cell activation and turnover. J Acquir Immune Defic Syndr. 2003;33:125-133.
55. Deeks SG, Wrin T, Liegler T, et al. Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med. 2001;344: 472-480.
56. Daar ES, Kesler KL, Wrin T, et al. HIV-1 pol replication capacity predicts disease progression. AIDS. 2005;19:871-877.
57. Barbour JD, Hecht FM, Wrin T, et al. Higher CD4+ T cell counts associated with low viral pol replication capacity among treatment-naive adults in early HIV-1 infection. J Infect Dis. 2004;190:251-256.
58. Barbour JD, Hecht FM, Little SJ, et al. Greater CD4 T-cell gains after one year of antiretroviral therapy are associated with lower HIV-1 pol replication capacity. AIDS. 2006;20:2123-2125.
59. Hicks C, Eron J, Keiser P, et al. HIV-1 replication capacity as an independent predictor of pre-treatment CD4 lymphocyte count. Presented at: 12th Conference on Retroviruses and Opportunistic Infections; 2005; Boston, MA. Abstract 345.
60. De Luca A, Weidler J, Di Giambenedetto S, et al. Association of HIV-1 replication capacity with treatment outcomes in patients with virologic treatment failure. J Acquir Immune Defic Syndr. 2007;45:411-417.
61. Haubrich R, Wrin T, Hellmann N, et al, and the CCTG. Replication Capacity (RC) as a Predictor of Immunologic and Virologic Benefit Despite Virologic Failure of an Antiretroviral Regimen. Antivir Ther. 2002;7:S101.
62. Shafer RW, Smeaton LM, Robbins GK, et al. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003;349:2304-2315.
63. Robbins GK, De Gruttola V, Shafer RW, et al. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003;349:2293-2303.
64. Petropoulos CJ, Parkin NT, Limoli KL, et al. A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2000;44:920-928.
65. Campbell TB, Schneider K, Wrin T, et al. Relationship between in vitro human immunodeficiency virus type 1 replication rate and virus load in plasma. J Virol. 2003;77:12105-12112.
66. Moore DM, Hogg RS, Yip B, et al. Discordant immunologic and virologic responses to highly active antiretroviral therapy are associated with increased mortality and poor adherence to therapy. J Acquir Immune Defic Syndr. 2005;40:288-293.
67. Schechter M, Tuboi SH. Discordant immunological and virological responses to antiretroviral therapy. J Antimicrob Chemother. 2006;58: 506-510.
68. Carbone J, Gil J, Benito JM, et al. Increased levels of activated subsets of CD4 T cells add to the prognostic value of low CD4 T cell counts in a cohort of HIV-infected drug users. AIDS. 2000;14:2823-2829.
69. Leng Q, Borkow G, Weisman Z, et al. Immune activation correlates better than HIV plasma viral load with CD4 T-cell decline during HIV infection. J Acquir Immune Defic Syndr. 2001;27:389-397.
70. Hazenberg MD, Otto SA, van Benthem BH, et al. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS. 2003;17:1881-1888.
71. Choudhary SK, Vrisekoop N, Jansen CA, et al. Low immune activation despite high levels of pathogenic human immunodeficiency virus type 1 results in long-term asymptomatic disease. J Virol. 2007;81: 8838-8842.
72. Sousa AE, Carneiro J, Meier-Schellersheim M, et al. 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. J Immunol. 2002;169: 3400-3406.
73. Deeks SG, Hoh R, Grant RM, et al. CD4+ T cell kinetics and activation in human immunodeficiency virus-infected patients who remain viremic despite long-term treatment with protease inhibitor-based therapy. J Infect Dis. 2002;185:315-323.
74. Silvestri G, Sodora DL, Koup RA, et al. Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity. 2003;18:441-452.
75. Broussard SR, Staprans SI, White R, et al. Simian immunodeficiency virus replicates to high levels in naturally infected African green monkeys without inducing immunologic or neurologic disease. J Virol. 2001;75: 2262-2275.
76. Mehandru S, Poles MA, Tenner-Racz K, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 2004;200:761-770.
77. Brenchley JM, Schacker TW, Ruff LE, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med. 2004;200:749-759.
78. Hazenberg MD, Hamann D, Schuitemaker H, et al. T cell depletion in HIV-1 infection: how CD4+ T cells go out of stock. Nat Immunol. 2000; 1: 285-289.
79. Pakker NG, Notermans DW, de Boer RJ, et al. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat Med. 1998; 4:208-214.
80. +lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues. J Clin Invest. 1999;103:1391-1398.
81. Lederman MM, Connick E, Landay A, et al. Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315. J Infect Dis. 1998;178:70-79.
82. Montaner J, Lederman M, Hill A, et al. Discordant CD4/RNA responses to HAARTare strongly associated with high-baseline CD4 count and low HIVRNA: analysis of 406 naive patients. Presented at: Abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy; San Francisco, CA, September 26-29, 1999. Abstract 1993.
83. Lederman MM, Valdez H. Immune restoration with antiretroviral therapies: implications for clinical management. JAMA. 2000;284:223-228.
84. Daar ES, Kesler KL, Petropoulos CJ, et al. Baseline HIV type 1 coreceptor tropism predicts disease progression. Clin Infect Dis. 2007;45:643-649.