Measuring the latent reservoir in vivo

Journal of Clinical Investigation

Volumn 126, Issue 2, 2016, Pages 464-472

  Massanella, Marta ^a   Richman, Douglas D ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

VIRUS RNA; VIRUS DNA;

HUMAN IMMUNODEFICIENCY VIRUS; IN VIVO STUDY; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROVIRUS; REPRODUCIBILITY; RESERVOIR; REVIEW; RNA TRANSCRIPTION; SENSITIVITY AND SPECIFICITY; VIREMIA; VIRION; VIROGENESIS; VIRUS CULTURE; VIRUS LATENCY; VIRUS REPLICATION; VIRUS TRANSCRIPTION; ANIMAL; BLOOD; CD4+ T LYMPHOCYTE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; METABOLISM; VIROLOGY;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; DNA, VIRAL; HIV INFECTIONS; HIV-1; HUMANS; SENSITIVITY AND SPECIFICITY;

EID: 84956951516     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI80567     Document Type: Review

References (98)

1. Chomont N, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009;15(8):893-900.
2. Brenchley JM, et al. T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis. J Virol. 2004;78(3):1160-1168.
3. Buzon MJ, et al. HIV-1 persistence in CD4+ T cells with stem cell-like properties. Nat Med. 2014;20(2):139-142.
4. Strain MC, et al. Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1. J Infect Dis. 2005;191(9):1410-1418.
5. Zhang ZQ, et al. Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection. Proc Natl Acad Sci U S A. 1998;95(3):1154-1159.
6. Blum KS, Pabst R. Lymphocyte numbers and subsets in the human blood. Do they mirror the situation in all organs? Immunol Lett. 2007;108(1):45-51.
7. Chun TW, et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature. 1997;387(6629):183-188.
8. Finzi D, et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997;278(5341):1295-1300.
9. Wong JK, et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science. 1997;278(5341):1291-1295.
10. Eriksson S, et al. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLoS Pathog. 2013;9(2):e1003174.
11. Rouzioux C, Malard A, Avittand-Finoil V. Quantification of total HIV1-DNA in peripheral blood mononuclear cells. Methods Mol Biol. 2014;1087:261-270.
12. Vandergeeten C, et al. Cross-clade ultrasensitive PCR-based assays to measure HIV persistence in large-cohort studies. J Virol. 2014;88(21):12385-12396.
13. Oliveira MF, et al. Comparative analysis of cell-associated HIV DNA levels in cerebrospinal fluid and peripheral blood by droplet digital PCR. PLoS One. 2015;10(10):e0139510.
14. Martinez-Bonet M, et al. Establishment and replenishment of the viral reservoir in perinatally HIV-1-infected children initiating very early antiretroviral therapy. Clin Infect Dis. 2015;61(7):1169-1178.
15. Christopherson C, et al. PCR-Based assay to quantify human immunodeficiency virus type 1 DNA in peripheral blood mononuclear cells. J Clin Microbiol. 2000;38(2):630-634.
16. Strain MC, et al. Highly Precise measurement of HIV DNA by droplet digital PCR. PLoS One. 2013;8(4):e55943.
17. Massanella M, Gianella S, Lada SM, Richman DD, Strain MC. Quantification of Total and 2-LTR (Long terminal repeat) HIV DNA, HIV RNA and Herpesvirus DNA in PBMCs. Bio-protocol. 2015;5(11):e1492. http://www.bio-protocol.org/e1492.
18. O'Doherty U, Swiggard WJ, Jeyakumar D, McGain D, Malim MH. A sensitive, quantitative assay for human immunodeficiency virus type 1 integration. J Virol. 2002;76(21):10942-10950.
19. Mexas AM, et al. Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials. AIDS. 2012;26(18):2295-2306.
20. Liszewski MK, Yu JJ, O'Doherty U. Detecting HIV-1 integration by repetitive-sampling Alu-gag PCR. Methods. 2009;47(4):254-260.
21. Brady T, et al. Quantitation of HIV DNA inte- gration: effects of differential integration site distributions on Alu-PCR assays. J Virol Methods. 2013;189(1):53-57.
22. Koelsch KK, et al. Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro. J Infect Dis. 2008;197(3):411-419.
23. Vandegraaff N, Kumar R, Burrell CJ, Li P. Kinetics of human immunodeficiency virus type 1 (HIV) DNA integration in acutely infected cells as determined using a novel assay for detection of integrated HIV DNA. J Virol. 2001;75(22):11253-11260.
24. Buzon MJ, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med. 2010;16(4):460-465.
25. Hatano H, et al. Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV infection: a randomized, placebo-controlled trial. J Infect Dis. 2013;208(9):1436-1442.
26. Pierson TC, et al. Intrinsic stability of episomal circles formed during human immunodeficiency virus type 1 replication. J Virol. 2002;76(8):4138-4144.
27. Bushman F. Measuring covert HIV replication during HAART: the abundance of 2-LTR circles is not a reliable marker. AIDS. 2003;17(5):749-750.
28. Zhu W, et al. Rapid Turnover of 2-LTR HIV-1 DNA during early stage of highly active antiretroviral therapy. PLoS One. 2011;6(6):e21081.
29. Pace MJ, et al. Directly infected resting CD4+ T cells can produce HIV Gag without spreading infection in a model of HIV latency. PLoS Pathog. 2012;8(7):e1002818.
30. Gianella S, et al. Cytomegalovirus replication in semen is associated with higher levels of proviral HIV DNA and CD4+ T cell activation during antiretroviral treatment. J Virol. 2014;88(14):7818-7827.
31. Bosman KJ, et al. Comparison of digital PCR platforms and semi-nested qPCR as a tool to determine the size of the HIV reservoir. Sci Rep. 2015;5:13811.
32. Soriano-Sarabia N, et al. Peripheral Vγ9Vδ2 T cells are a novel reservoir of latent HIV Infection. PLoS Pathog. 2015;11(10):e1005201.
33. Puertas MC, et al. Effect of lithium on HIV-1 expression and proviral reservoir size in the CD4+ T cells of antiretroviral therapy suppressed patients. AIDS. 2014;28(14):2157-2159.
34. Fischer M, et al. Attenuated and nonproductive viral transcription in the lymphatic tissue of HIV-1-infected patients receiving potent antiretroviral therapy. J Infect Dis. 2004;189(2):273-285.
35. Lassen KG, Ramyar KX, Bailey JR, Zhou Y, Siliciano RF. Nuclear retention of multiply spliced HIV-1 RNA in resting CD4+ T cells. PLoS Pathog. 2006;2(7):e68.
36. Pasternak AO, et al. Highly sensitive methods based on seminested real-time reverse transcription-PCR for quantitation of human immunodeficiency virus type 1 unspliced and multiply spliced RNA and proviral DNA. J Clin Microbiol. 2008;46(7):2206-2211.
37. Pasternak AO, et al. Cellular levels of HIV unspliced RNA from patients on combination antiretroviral therapy with undetectable plasma viremia predict the therapy outcome. PLoS One. 2009;4(12):e8490.
38. Schmid A, et al. Profound depletion of HIV-1 transcription in patients initiating antiretroviral therapy during acute infection. PLoS One. 2010;5(10):e13310.
39. Kiselinova M, Pasternak AO, De Spiegelaere W, Vogelaers D, Berkhout B, Vandekerckhove L. Comparison of droplet digital PCR and seminested real-time PCR for quantification of cell-associated HIV-1 RNA. PLoS One. 2014;9(1):e85999.
40. Yerly S, Rutschmann OT, Opravil M, Marchal F, Hirschel B, Perrin L. Cell-associated HIV-1 RNA in blood as indicator of virus load in lymph nodes. The Swiss HIV Cohort Study. J Infect Dis. 1999;180(3):850-853.
41. Fischer M, et al. Highly sensitive methods for quantitation of human immunodeficiency virus type 1 RNA from plasma, cells, and tissues. J Clin Microbiol. 1999;37(5):1260-1264.
42. Nugent CT, et al. Detection of HIV-1 in alternative specimen types using the APTIMA HIV-1 RNA Qualitative Assay. J Virol Methods. 2009;159(1):10-14.
43. Hatano H, et al. A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. J Infect Dis. 2011;203(7):960-968.
44. Gianella S, et al. Cytomegalovirus DNA in semen and blood is associated with higher levels of proviral HIV DNA. J Infect Dis. 2013;207(6):898-902.
45. Bullen CK, Laird GM, Durand CM, Siliciano JD, Siliciano RF. New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo. Nat Med. 2014;20(4):425-429.
46. Shan L, et al. A novel PCR assay for quantification of HIV-1 RNA. J Virol. 2013;87(11):6521-6525.
47. Dornadula G, et al. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. JAMA. 1999;282(17):1627-1632.
48. Palmer S, et al. New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol. 2003;41(10):4531-4536.
49. Palmer S, et al. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A. 2008;105(10):3879-3884.
50. Sahu GK, Sarria JC, Cloyd MW. Recovery of replication-competent residual HIV-1 from plasma of a patient receiving prolonged, suppressive highly active antiretroviral therapy. J Virol. 2010;84(16):8348-8352.
51. Hermankova M, et al. Analysis of human immunodeficiency virus type 1 gene expression in latently infected resting CD4+ T lymphocytes in vivo. J Virol. 2003;77(13):7383-7392.
52. Kieffer TL, et al. Genotypic analysis of HIV-1 drug resistance at the limit of detection: virus production without evolution in treated adults with undetectable HIV loads. J Infect Dis. 2004;189(8):1452-1465.
53. Bailey JR, et al. 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. 2006;80(13):6441-6457.
54. Wagner TA, et al. HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection. Science. 2014;345(6196):570-573.
55. Maldarelli F, et al. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells. Science. 2014;345(6193):179-183.
56. Cillo AR, et al. Improved single-copy assays for quantification of persistent HIV-1 viremia in patients on suppressive antiretroviral therapy. J Clin Microbiol. 2014;52(11):3944-3951.
57. Chun TW, et al. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 1997;94(24):13193-13197.
58. Ylisastigui L, Archin NM, Lehrman G, Bosch RJ, Margolis DM. Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression. AIDS. 2004;18(8):1101-1108.
59. Archin NM, et al. Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells. AIDS. 2008;22(10):1131-1135.
60. Lehrman G, et al. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet. 2005;366(9485):549-555.
61. Siliciano JD, et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med. 2003;9(6):727-728.
62. Finzi D, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med. 1999;5(5):512-517.
63. Siliciano JD, Siliciano RF. Enhanced culture assay for detection and quantitation of latently infected, resting CD4+ T-cells carrying replicationcompetent virus in HIV-1-infected individuals. Methods Mol Biol. 2005;304:3-15.
64. Soriano-Sarabia N, et al. Quantitation of replication-competent HIV-1 in populations of resting CD4+ T cells. J Virol. 2014;88(24):14070-14077.
65. Morón-López S, et al. Short-term treatment with IFNα diminishes expression of HIV-1 and reduces CD4+ T-cell activation in HIV/HCVcoinfected patients on antiretroviral therapy [published online ahead of print: November 1, 2015]. J Infect Dis. doi:10.1093/infdis/jiv521.
66. Rosenbloom DI, et al. Designing and interpreting limiting dilution assays: general principles and applications to the latent reservoir for Human Immunodeficiency Virus-1. Open Forum Infect Dis. 2015;2(4):ofv123.
67. Ho YC, et al. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell. 2013;155(3):540-551.
68. Laird GM, et al. Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay. PLoS Pathog. 2013;9(5):e1003398.
69. Richman DD. Detection and Quantification of HIV Reservoirs: Measuring the latent reservoir. Presented at: Keystone Symposia. Mechanisms of HIV Persistence: Implications for a Cure 2015; April 26-May 1, 2015; Boston, Massachusetts, USA.
70. Weinberger AD, Weinberger LS. Stochastic fate selection in HIV-infected patients. Cell. 2013;155(3):497-499.
71. Rosenbloom DIS, Elliott O, Hill AL, Henrich TJ, Siliciano JL, Siliciano JF. Designing and interpreting limiting dilution assays: general principles and applications to the latent reservoir for Human Immunodeficiency Virus-1. Open Forum Infect Dis. 2015;2(4).
72. Mohammadi P, et al. Dynamics of HIV latency and reactivation in a primary CD4+ T cell model. PLoS Pathog. 2014;10(5):e1004156.
73. Cillo AR, et al. Quantification of HIV-1 latency reversal in resting CD4+ T cells from patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A. 2014;111(19):7078-7083.
74. Laird GM, et al. Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations. J Clin Invest. 2015;125(5):1901-1912.
75. Elliott JH, et al. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog. 2014;10(11):e1004473.
76. Procopio FA, et al. A novel assay to measure the magnitude of the inducible viral reservoir in HIV-infected individuals. EBioMedicine. 2015;2(8):872-881.
77. Webster WA, Casey GA, Charlton KM. The mouse inoculation test in rabies diagnosis: early diagnosis in mice during the incubation period. Can J Comp Med. 1976;40(3):322-325.
78. Burnet FM. The use of the developing egg in virus research. Med Res Council Spec Rep Ser. 1936;220.
79. Okoye AA, et al. Early Treatment in Acute SIV Infection Limits the Size and Distribution of the Viral Reservoir. Presented at: Conference on Retroviruses and Opportunistic Infections 2014; March 3-6, 2014; Boston, Massachusetts, USA. Abstract 136LB.
80. Hansen SG, et al. Immune clearance of highly pathogenic SIV infection. Nature. 2013;502(7469):100-104.
81. Lifson JD, et al. Evaluation of the safety, immunogenicity, and protective efficacy of whole inactivated simian immunodeficiency virus (SIV) vaccines with conformationally and functionally intact envelope glycoproteins. AIDS Res Hum Retroviruses. 2004;20(7):772-787.
82. Denton PW, Garcia JV. Humanized mouse models of HIV infection. AIDS Rev. 2011;13(3):135-148.
83. Metcalf Pate KA, et al. A murine viral outgrowth assay to detect residual HIV type 1 in patients with undetectable viral loads. J Infect Dis. 2015;212(9):1387-1396.
84. Wit FW, et al. Safety of long-term interruption of successful antiretroviral therapy: the ATHENA cohort study. AIDS. 2005;19(3):345-348.
85. Campbell JH, Hearps AC, Martin GE, Williams KC, Crowe SM. The importance of monocytes and macrophages in HIV pathogenesis, treatment, and cure. AIDS. 2014;28(15):2175-2187.
86. Calantone N, et al. Tissue myeloid cells in SIV-infected primates acquire viral DNA through phagocytosis of infected T cells. Immunity. 2014;41(3):493-502.
87. Haase AT. Population biology of HIV-1 infection: viral and CD4+ T cell demographics and dynamics in lymphatic tissues. Annu Rev Immunol. 1999;17:625-656.
88. Pakker NG, 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(2):208-214.
89. Costiniuk CT, Jenabian MA. Cell-to-cell transfer of HIV infection: implications for HIV viral persistence. J Gen Virol. 2014;95(pt 11):2346-2355.
90. Sathaliyawala T, et al. Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. Immunity. 2013;38(1):187-197.
91. Yukl SA, et al. The distribution of HIV DNA and RNA in cell subsets differs in gut and blood of HIV-positive patients on ART: implications for viral persistence. J Infect Dis. 2013;208(8):1212-1220.
92. Cu-Uvin S, et al. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS. 2010;24(16):2489-2497.
93. Lambert-Niclot S, et al. Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma on a 2002-2011 survey. AIDS. 2012;26(8):971-975.
94. Bednar MM, et al. Compartmentalization, viral evolution, and viral latency of HIV in the CNS. Curr HIV/AIDS Rep. 2015;12(2):262-271.
95. Hellmuth J, Valcour V, Spudich S. CNS reservoirs for HIV: implications for eradication. J Virus Erad. 2015;1(2):67-71.
96. Pillai SK, et al. Semen-specific genetic characteristics of human immunodeficiency virus type 1 env. J Virol. 2005;79(3):1734-1742.
97. Henrich TJ, et al. Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Ann Intern Med. 2014;161(5):319-327.
98. Luzuriaga K, et al. Viremic relapse after HIV-1 remission in a perinatally infected child. N Engl J Med. 2015;372(8):786-788.