Comparative Analysis of Measures of Viral Reservoirs in HIV-1 Eradication Studies

PLoS Pathogens

Volumn 9, Issue 2, 2013, Pages

  Eriksson, Susanne ^a   Graf, Erin H ^b   Dahl, Viktor ^a   Strain, Matthew C ^c   Yukl, Steven A ^d,e   Lysenko, Elena S ^b   Bosch, Ronald J ^f   Lai, Jun ^g   Chioma, Stanley ^g   Emad, Fatemeh ^g   Abdel Mohsen, Mohamed ^e   Hoh, Rebecca ^e   Hecht, Frederick ^e   Hunt, Peter ^e   Somsouk, Ma ^e   Wong, Joseph ^d,e   Johnston, Rowena ^h   Siliciano, Robert F ^g,i   Richman, Douglas D ^c   O'Doherty, Una ^b   Palmer, Sarah ^a   Deeks, Steven G ^e   Siliciano, Janet D ^g,i   more..

^a KAROLINSKA INSTITUTE   (Sweden)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d VETERANS AFFAIRS MEDICAL CENTER   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^g JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^h Foundation for AIDS Research   (United States)

ⁱ HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR; ATAZANAVIR PLUS RITONAVIR; DARUNAVIR PLUS RITONAVIR; DIDANOSINE; EFAVIRENZ; EMTRICITABINE; ETRAVIRINE; FOSAMPRENAVIR; FOSAMPRENAVIR PLUS RITONAVIR; LAMIVUDINE; NEVIRAPINE; RALTEGRAVIR; STAVUDINE; TENOFOVIR DISOPROXIL;

ADULT; ARTICLE; CD4+ T LYMPHOCYTE; CLINICAL ARTICLE; COMPARATIVE STUDY; DISEASE CARRIER; DISEASE CONTROL; FEMALE; HIGH THROUGHPUT SCREENING; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN TISSUE; LIMIT OF DETECTION; MALE; PERIPHERAL BLOOD MONONUCLEAR CELL; POLYMERASE CHAIN REACTION; PROVIRUS; RECTUM BIOPSY; VIREMIA; VIROGENESIS; VIRUS GENOME; WESTERN BLOTTING;

ADULT; AGED; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CD4-POSITIVE T-LYMPHOCYTES; DISEASE RESERVOIRS; DNA, VIRAL; FEMALE; HIV; HIV INFECTIONS; HUMANS; LEUKOCYTES, MONONUCLEAR; LONGITUDINAL STUDIES; MALE; MIDDLE AGED; POLYMERASE CHAIN REACTION; PROVIRUSES; RNA, VIRAL; VIRAL LOAD; VIRUS INTEGRATION;

EID: 84873472629     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003174     Document Type: Article

References (84)

1. Gulick RM, Mellors JW, Havlir D, Eron JJ, Gonzalez C, et al. (1997) Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med 337: 734-739.
2. Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, et al. (1997) A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS clinical trials group 320 study team. N Engl J Med 337: 725-733.
3. Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, et al. (1997) Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 387: 188-191.
4. Chun TW, Finzi D, Margolick J, Chadwick K, Schwartz D, et al. (1995) In vivo fate of HIV-1-infected T cells: Quantitative analysis of the transition to stable latency. Nat Med 1: 1284-1290.
5. Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, et al. (1997) Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387: 183-188.
6. Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, et al. (1997) Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278: 1295-1300.
7. Wong JK, Hezareh M, Gunthard HF, Havlir DV, Ignacio CC, et al. (1997) Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278: 1291-1295.
8. Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, et al. (1997) Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A 94: 13193-13197.
9. Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, et al. (1999) Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 5: 512-517.
10. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, et al. (2003) Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med 9: 727-728.
11. Strain MC, Gunthard HF, Havlir DV, Ignacio CC, Smith DM, et al. (2003) Heterogeneous clearance rates of long-lived lymphocytes infected with HIV: Intrinsic stability predicts lifelong persistence. Proc Natl Acad Sci U S A 100: 4819-4824.
12. Davey RT Jr, Bhat N, Yoder C, Chun TW, Metcalf JA, et al. (1999) HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S A 96: 15109-15114.
13. Chun TW, Justement JS, Murray D, Hallahan CW, Maenza J, et al. (2010) Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: Implications for eradication. AIDS 24: 2803-2808.
14. Joos B, Fischer M, Kuster H, Pillai SK, Wong JK, et al. (2008) HIV rebounds from latently infected cells, rather than from continuing low-level replication. Proc Natl Acad Sci U S A 105: 16725-16730.
15. Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, et al. (2009) The challenge of finding a cure for HIV infection. Science 323: 1304-1307.
16. Chun TW, Engel D, Mizell SB, Ehler LA, Fauci AS, (1998) Induction of HIV-1 replication in latently infected CD4+ T cells using a combination of cytokines. J Exp Med 188: 83-91.
17. Scripture-Adams DD, Brooks DG, Korin YD, Zack JA, (2002) Interleukin-7 induces expression of latent human immunodeficiency virus type 1 with minimal effects on T-cell phenotype. J Virol 76: 13077-13082.
18. Wang FX, Xu Y, Sullivan J, Souder E, Argyris EG, et al. (2005) IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART. J Clin Invest 115: 128-137.
19. Nunnari G, Pomerantz RJ, (2005) IL-7 as a potential therapy for HIV-1-infected individuals. Expert Opin Biol Ther 5: 1421-1426.
20. Kulkosky J, Culnan DM, Roman J, Dornadula G, Schnell M, et al. (2001) Prostratin: Activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART. Blood 98: 3006-3015.
21. Korin YD, Brooks DG, Brown S, Korotzer A, Zack JA, (2002) Effects of prostratin on T-cell activation and human immunodeficiency virus latency. J Virol 76: 8118-8123.
22. Brooks DG, Hamer DH, Arlen PA, Gao L, Bristol G, et al. (2003) Molecular characterization, reactivation, and depletion of latent HIV. Immunity 19: 413-423.
23. Brooks DG, Arlen PA, Gao L, Kitchen CM, Zack JA, (2003) Identification of T cell-signaling pathways that stimulate latent HIV in primary cells. Proc Natl Acad Sci U S A 100: 12955-12960.
24. Williams SA, Chen LF, Kwon H, Fenard D, Bisgrove D, et al. (2004) Prostratin antagonizes HIV latency by activating NF-kappaB. J Biol Chem 279: 42008-42017.
25. Lehrman G, Hogue IB, Palmer S, Jennings C, Spina CA, et al. (2005) Depletion of latent HIV-1 infection in vivo: A proof-of-concept study. Lancet 366: 549-555.
26. Archin NM, Espeseth A, Parker D, Cheema M, Hazuda D, et al. (2009) Expression of latent HIV induced by the potent HDAC inhibitor suberoylanilide hydroxamic acid. AIDS Res Hum Retroviruses 25: 207-212.
27. Contreras X, Schweneker M, Chen CS, McCune JM, Deeks SG, et al. (2009) Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells. J Biol Chem 284: 6782-6789.
28. Kauder SE, Bosque A, Lindqvist A, Planelles V, Verdin E, (2009) Epigenetic regulation of HIV-1 latency by cytosine methylation. PLoS Pathog 5: e1000495.
29. Blazkova J, Trejbalova K, Gondois-Rey F, Halfon P, Philibert P, et al. (2009) CpG methylation controls reactivation of HIV from latency. PLoS Pathog 5: e1000554.
30. Yang HC, Xing S, Shan L, O'Connell K, Dinoso J, et al. (2009) Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation. J Clin Invest 119: 3473-3486.
31. Xing S, Bullen CK, Shroff NS, Shan L, Yang HC, et al. (2011) Disulfiram reactivates latent HIV-1 in a bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation. J Virol 85: 6060-6064.
32. Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, et al. (2012) Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487: 482-485.
33. Siliciano JD, Siliciano RF, (2005) Enhanced culture assay for detection and quantitation of latently infected, resting CD4+ T-cells carrying replication-competent virus in HIV-1-infected individuals. Methods Mol Biol 304: 3-15.
34. Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, et al. (1990) HIV-1 entry into quiescent primary lymphocytes: Molecular analysis reveals a labile, latent viral structure. Cell 61: 213-222.
35. Bukrinsky MI, Stanwick TL, Dempsey MP, Stevenson M, (1991) Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Science 254: 423-427.
36. Blankson JN, Finzi D, Pierson TC, Sabundayo BP, Chadwick K, et al. (2000) Biphasic decay of latently infected CD4+ T cells in acute human immunodeficiency virus type 1 infection. J Infect Dis 182: 1636-1642.
37. Pierson TC, Zhou Y, Kieffer TL, Ruff CT, Buck C, et al. (2002) Molecular characterization of preintegration latency in human immunodeficiency virus type 1 infection. J Virol 76: 8518-8531.
38. Mexas AM, Graf EH, Pace MJ, Papasavvas E, Azzoni L, et al. (2012) Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials. AIDS 26: 2295-306.
39. O'Doherty U, Swiggard WJ, Jeyakumar D, McGain D, Malim MH, (2002) A sensitive, quantitative assay for human immunodeficiency virus type 1 integration. J Virol 76: 10942-10950.
40. Yu JJ, Wu TL, Liszewski MK, Dai J, Swiggard WJ, et al. (2008) A more precise HIV integration assay designed to detect small differences finds lower levels of integrated DNA in HAART treated patients. Virology 379: 78-86.
41. Sanchez G, Xu X, Chermann JC, Hirsch I, (1997) Accumulation of defective viral genomes in peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected individuals. J Virol 71: 2233-2240.
42. Kieffer TL, Kwon P, Nettles RE, Han Y, Ray SC, et al. (2005) G→A hypermutation in protease and reverse transcriptase regions of human immunodeficiency virus type 1 residing in resting CD4+ T cells in vivo. J Virol 79: 1975-1980.
43. Chun TW, Nickle DC, Justement JS, Meyers JH, Roby G, et al. (2008) Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis 197: 714-720.
44. Yukl SA, Gianella S, Sinclair E, Epling L, Li Q, et al. (2010) Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy. J Infect Dis 202: 1553-1561.
45. Dornadula G, Zhang H, VanUitert B, Stern J, Livornese L Jr, et al. (1999) Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. JAMA 282: 1627-1632.
46. Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, et al. (2003) New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol 41: 4531-4536.
47. Palmer S, Maldarelli F, Wiegand A, Bernstein B, Hanna GJ, et al. (2008) Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A 105: 3879-3884.
48. Dinoso JB, Kim SY, Wiegand AM, Palmer SE, Gange SJ, et al. (2009) Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci U S A 106: 9403-9408.
49. McMahon D, Jones J, Wiegand A, Gange SJ, Kearney M, et al. (2010) Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy. Clin Infect Dis 50: 912-919.
50. Gandhi RT, Zheng L, Bosch RJ, Chan ES, Margolis DM, et al. (2010) The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: A randomized controlled trial. PLoS Med 7: e1000321.
51. The International AIDS Society Scientific Working Group on HIV Cure (2012) Deeks SG, Autran B, Berkhout B, Benkirane M, et al. (2012) Towards an HIV cure: A global scientific strategy. Nat Rev Immunol 12: 607-614.
52. Chun TW, Engel D, Berrey MM, Shea T, Corey L, et al. (1998) Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection. Proc Natl Acad Sci U S A 95: 8869-8873.
53. Strain MC, Lada SM, Luong T, Rought SE, Gianella S, et al. (2013) Highly accurate measurement of HIV DNA by droplet digital PCR. PLOS ONE In press.
54. Chun TW, Nickle DC, Justement JS, Large D, Semerjian A, et al. (2005) HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir. J Clin Invest 115: 3250-3255.
55. Graf EH, Mexas AM, Yu JJ, Shaheen F, Liszewski MK, et al. (2011) Elite suppressors harbor low levels of integrated HIV DNA and high levels of 2-LTR circular HIV DNA compared to HIV+ patients on and off HAART. PLoS Pathog 7: e1001300.
56. Han Y, Lassen K, Monie D, Sedaghat AR, Shimoji S, et al. (2004) Resting CD4+ T cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals carry integrated HIV-1 genomes within actively transcribed host genes. J Virol 78: 6122-6133.
57. Veazey RS, DeMaria M, Chalifoux LV, Shvetz DE, Pauley DR, et al. (1998) Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280: 427-431.
58. Guadalupe M, Reay E, Sankaran S, Prindiville T, Flamm J, et al. (2003) 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. J Virol 77: 11708-11717.
59. Li Q, Duan L, Estes JD, Ma ZM, Rourke T, et al. (2005) Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 434: 1148-1152.
60. Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, et al. (2004) CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 200: 749-759.
61. Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, et al. (2005) Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 434: 1093-1097.
62. Sharkey ME, Teo I, Greenough T, Sharova N, Luzuriaga K, et al. (2000) Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy. Nat Med 6: 76-81.
63. Pierson TC, Kieffer TL, Ruff CT, Buck C, Gange SJ, et al. (2002) Intrinsic stability of episomal circles formed during human immunodeficiency virus type 1 replication. J Virol 76: 4138-4144.
64. Butler SL, Johnson EP, Bushman FD, (2002) Human immunodeficiency virus cDNA metabolism: Notable stability of two-long terminal repeat circles. J Virol 76: 3739-3747.
65. Sharkey M, Triques K, Kuritzkes DR, Stevenson M, (2005) In vivo evidence for instability of episomal human immunodeficiency virus type 1 cDNA. J Virol 79: 5203-5210.
66. Buzon MJ, Massanella M, Llibre JM, Esteve A, Dahl V, et al. (2010) HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med 16: 460-465.
67. Maldarelli F, Palmer S, King MS, Wiegand A, Polis MA, et al. (2007) ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog 3: e46.
68. Zhou Y, Zhang H, Siliciano JD, Siliciano RF, (2005) Kinetics of human immunodeficiency virus type 1 decay following entry into resting CD4+ T cells. J Virol 79: 2199-2210.
69. Bailey JR, Sedaghat AR, Kieffer T, Brennan T, Lee PK, et al. (2006) Residual human immunodeficiency virus type 1 viremia in some patients on antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4+ T cells. J Virol 80: 6441-6457.
70. Sahu GK, Paar D, Frost SD, Smith MM, Weaver S, et al. (2009) Low-level plasma HIVs in patients on prolonged suppressive highly active antiretroviral therapy are produced mostly by cells other than CD4 T-cells. J Med Virol 81: 9-15.
71. Brennan TP, Woods JO, Sedaghat AR, Siliciano JD, Siliciano RF, et al. (2009) Analysis of human immunodeficiency virus type 1 viremia and provirus in resting CD4+ T cells reveals a novel source of residual viremia in patients on antiretroviral therapy. J Virol 83: 8470-8481.
72. Anton PA, Mitsuyasu RT, Deeks SG, Scadden DT, Wagner B, et al. (2003) Multiple measures of HIV burden in blood and tissue are correlated with each other but not with clinical parameters in aviremic subjects. AIDS 17: 53-63.
73. Chun TW, Murray D, Justement JS, Hallahan CW, Moir S, et al. (2011) Relationship between residual plasma viremia and the size of HIV proviral DNA reservoirs in infected individuals receiving effective antiretroviral therapy. J Infect Dis 204: 135-138.
74. Murray JM, McBride K, Boesecke C, Bailey M, Amin J, et al. (2012) Integrated HIV DNA accumulates prior to treatment while episomal HIV DNA records ongoing transmission afterwards. AIDS 26: 543-550.
75. He G, Ylisastigui L, Margolis DM, (2002) The regulation of HIV-1 gene expression: The emerging role of chromatin. DNA Cell Biol 21: 697-705.
76. Lenasi T, Contreras X, Peterlin BM, (2008) Transcriptional interference antagonizes proviral gene expression to promote HIV latency. Cell Host Microbe 4: 123-133.
77. Han Y, Lin YB, An W, Xu J, Yang HC, et al. (2008) Orientation-dependent regulation of integrated HIV-1 expression by host gene transcriptional readthrough. Cell Host Microbe 4: 134-146.
78. Panel on Antiretroviral Guidelines for Adults and Adolescents. (2009) Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at Http://Www.Aidsinfo.Nih.Gov/ContentFiles/AdultandAdolescentGL.Pdf.: 1-161.
79. Gandhi RT, Bosch RJ, Aga E, Albrecht M, Demeter LM, et al. (2010) No evidence for decay of the latent reservoir in HIV-1-infected patients receiving intensive enfuvirtide-containing antiretroviral therapy. J Infect Dis 201: 293-296.
80. Liszewski MK, Yu JJ, O'Doherty U, (2009) Detecting HIV-1 integration by repetitive-sampling alu-gag PCR. Methods 47: 254-260.
81. Critchfield JW, Lemongello D, Walker DH, Garcia JC, Asmuth DM, et al. (2007) Multifunctional human immunodeficiency virus (HIV) gag-specific CD8+ T-cell responses in rectal mucosa and peripheral blood mononuclear cells during chronic HIV type 1 infection. J Virol 81: 5460-5471.
82. Shacklett BL, Critchfield JW, Lemongello D, (2009) Isolating mucosal lymphocytes from biopsy tissue for cellular immunology assays. Methods Mol Biol 485: 347-356.
83. Fischer M, Huber W, Kallivroussis A, Ott P, Opravil M, et al. (1999) Highly sensitive methods for quantitation of human immunodeficiency virus type 1 RNA from plasma, cells, and tissues. J Clin Microbiol 37: 1260-1264.
84. Josefsson L, King MS, Makitalo B, Brannstrom J, Shao W, et al. (2011) Majority of CD4+ T cells from peripheral blood of HIV-1-infected individuals contain only one HIV DNA molecule. Proc Natl Acad Sci U S A 108: 11199-11204.