Residual viremia in an RT-SHIV rhesus macaque HAART model marked by the presence of a predominant plasma clone and a lack of viral evolution

PLoS ONE

Volumn 9, Issue 2, 2014, Pages

  Kauffman, Robert C ^a,b   Villalobos, Andradi ^a,b   Bowen, Joanne H ^a   Adamson, Lourdes ^a   Schinazi, Raymond F ^b,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c ATLANTA VA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMDOXOVIR; COMPLEMENTARY DNA; EFAVIRENZ; EMTRICITABINE; NUCLEOSIDE ANALOG; TENOFOVIR; VIRUS RNA; ZIDOVUDINE;

ADOLESCENT; AMINO ACID SUBSTITUTION; AMPLICON; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; FEMALE; GENE AMPLIFICATION; GENE FREQUENCY; GENETIC VARIABILITY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; LIMIT OF DETECTION; MOLECULAR CLONING; MUTATIONAL ANALYSIS; NONHUMAN; NUCLEIC ACID BASE SUBSTITUTION; PHYLOGENY; PREVALENCE; RESIDUAL LOW LEVEL VIREMIA; REVERSE TRANSCRIPTASE SIMIAN IMMUNODEFICIENCY VIRUS; RHESUS MONKEY; SENSITIVITY ANALYSIS; SEQUENCE ANALYSIS; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; SIMIAN IMMUNODEFICIENCY VIRUS; TREATMENT DURATION; VIRAL EVOLUTION; VIRAL PHENOMENA AND FUNCTIONS; VIREMIA; VIRUS LOAD; VIRUS REPLICATION; VIRUS SUPPRESSION;

ANIMALS; ANTI-RETROVIRAL AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; DISEASE MODELS, ANIMAL; FEMALE; GENE FREQUENCY; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; MACACA MULATTA; MONKEY DISEASES; MUTATION; PHYLOGENY; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; SIMIAN IMMUNODEFICIENCY VIRUS; VIRAL LOAD; VIREMIA;

EID: 84895541434     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0088258     Document Type: Article

References (78)

1. Thompson MA, Aberg JA, Hoy JF, Telenti A, Benson C, et al. (2012) Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. JAMA 308: 387-402.
2. 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.
3. 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. (Pubitemid 37259753)
4. Havlir DV, Strain MC, Clerici M, Ignacio C, Trabattoni D, et al. (2003) Productive infection maintains a dynamic steady state of residual viremia in human immunodeficiency virus type 1-infected persons treated with suppressive antiretroviral therapy for five years. J Virol 77: 11212-11219. (Pubitemid 37204311)
5. 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. (Pubitemid 351723493)
6. Di Mascio M, Markowitz M, Louie M, Hogan C, Hurley A, et al. (2003) Viral blip dynamics during highly active antiretroviral therapy. J Virol 77: 12165-12172. (Pubitemid 37339869)
7. Havlir DV, Bassett R, Levitan D, Gilbert P, Tebas P, et al. (2001) Prevalence and predictive value of intermittent viremia with combination hiv therapy. JAMA 286: 171-179. (Pubitemid 32640848)
8. Harrigan PR, Whaley M, Montaner JS (1999) Rate of HIV-1 RNA rebound upon stopping antiretroviral therapy. AIDS 13: F59-62. (Pubitemid 29240180)
9. Gunthard HF, Frost SD, Leigh-Brown AJ, Ignacio CC, Kee K, et al. (1999) Evolution of envelope sequences of human immunodeficiency virus type 1 in cellular reservoirs in the setting of potent antiviral therapy. J Virol 73: 9404-9412. (Pubitemid 29487096)
10. Ramratnam B, Mittler JE, Zhang L, Boden D, Hurley A, et al. (2000) The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy. Nat Med 6: 82-85. (Pubitemid 30048531)
11. Deeks SG, Wrin T, Liegler T, Hoh R, Hayden M, et al. (2001) Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med 344: 472-480. (Pubitemid 32164898)
12. 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. (Pubitemid 27495742)
13. 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. (Pubitemid 29220209)
14. 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. (Pubitemid 28350581)
15. 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.
16. Koppensteiner H, Brack-Werner R, Schindler M (2012) Macrophages and their relevance in Human Immunodeficiency Virus Type I infection. Retrovirology 9.
17. 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. (Pubitemid 43927447)
18. 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.
19. Chun TW, Davey RT, Jr., Ostrowski M, Shawn Justement J, Engel D, et al. (2000) Relationship between pre-existing viral reservoirs and the re-emergence of plasma viremia after discontinuation of highly active anti-retroviral therapy. Nat Med 6: 757-761. (Pubitemid 30469423)
20. Johnston R, Barre-Sinoussi F (2012) Controversies in HIV cure research. J Int AIDS Soc 15: 16.
21. 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.
22. Deeks SG (2011) HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med 62: 141-155.
23. Tobin NH, Learn GH, Holte SE, Wang Y, Melvin AJ, et al. (2005) Evidence that low-level viremias during effective highly active antiretroviral therapy result from two processes: expression of archival virus and replication of virus. J Virol 79: 9625-9634. (Pubitemid 41022306)
24. Shiu C, Cunningham CK, Greenough T, Muresan P, Sanchez-Merino V, et al. (2009) Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral therapy. J Virol 83: 9731-9742.
25. Anderson JA, Archin NM, Ince W, Parker D, Wiegand A, et al. (2011) Clonal sequences recovered from plasma from patients with residual HIV-1 viremia and on intensified antiretroviral therapy are identical to replicating viral RNAs recovered from circulating resting CD4+ T cells. J Virol 85: 5220-5223.
26. 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.
27. Mavigner M, Delobel P, Cazabat M, Dubois M, L'Faqihi-Olive FE, et al. (2009) HIV-1 Residual Viremia Correlates with Persistent T-Cell Activation in Poor Immunological Responders to Combination Antiretroviral Therapy. Plos One 4.
28. Zhang L, Chung C, Hu BS, He T, Guo Y, et al. (2000) Genetic characterization of rebounding HIV-1 after cessation of highly active antiretroviral therapy. J Clin Invest 106: 839-845.
29. Martinez-Picado J, Frost SD, Izquierdo N, Morales-Lopetegi K, Marfil S, et al. (2002) Viral evolution during structured treatment interruptions in chronically human immunodeficiency virus-infected individuals. J Virol 76: 12344-12348. (Pubitemid 35304333)
30. 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.
31. Kearney M, Spindler J, Shao W, Maldarelli F, Palmer S, et al. (2011) Genetic diversity of simian immunodeficiency virus encoding HIV-1 reverse transcriptase persists in macaques despite antiretroviral therapy. J Virol 85: 1067-1076.
32. North TW, Higgins J, Deere JD, Hayes TL, Villalobos A, et al. (2010) Viral sanctuaries during highly active antiretroviral therapy in a nonhuman primate model for AIDS. J Virol 84: 2913-2922.
33. Dinoso JB, Rabi SA, Blankson JN, Gama L, Mankowski JL, et al. (2009) A simian immunodeficiency virus-infected macaque model to study viral reservoirs that persist during highly active antiretroviral therapy. J Virol 83: 9247-9257.
34. Ambrose Z, Boltz V, Palmer S, Coffin JM, Hughes SH, et al. (2004) In vitro characterization of a simian immunodeficiency virus-human immunodeficiency virus (HIV) chimera expressing HIV type 1 reverse transcriptase to study antiviral resistance in pigtail macaques. J Virol 78: 13553-13561. (Pubitemid 39612755)
35. Shytaj IL, Norelli S, Chirullo B, Della Corte A, Collins M, et al. (2012) A Highly Intensified ART Regimen Induces Long-Term Viral Suppression and Restriction of the Viral Reservoir in a Simian AIDS Model. Plos Pathogens 8.
36. Uberla K, Stahl-Hennig C, Bottiger D, Matz-Rensing K, Kaup FJ, et al. (1995) Animal model for the therapy of acquired immunodeficiency syndrome with reverse transcriptase inhibitors. Proc Natl Acad Sci U S A 92: 8210-8214.
37. Hofman MJ, Higgins J, Matthews TB, Pedersen NC, Tan C, et al. (2004) Efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1. Antimicrob Agents Chemother 48: 3483-3490. (Pubitemid 39129349)
38. Johnson JA, Sax PE (2009) Antiretroviral therapy for treatment-naive patients: a review of recent literature and the updated guidelines. Curr Infect Dis Rep 11: 311-318.
39. Hammer SM, Eron JJ, Jr., Reiss P, Schooley RT, Thompson MA, et al. (2008) Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 300: 555-570.
40. North TW, Van Rompay KK, Higgins J, Matthews TB, Wadford DA, et al. (2005) Suppression of virus load by highly active antiretroviral therapy in rhesus macaques infected with a recombinant simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1. J Virol 79: 7349-7354. (Pubitemid 40756770)
41. Deere JD, Higgins J, Cannavo E, Villalobos A, Adamson LA, et al. (2010) Low-level viremia persists despite suppressive highly active antiretroviral therapy in rhesus macaques infected with RT-SHIV. In preparation.
42. Vandenbroucke I, Van Marck H, Verhasselt P, Thys K, Mostmans W, et al. (2011) Minor variant detection in amplicons using 454 massive parallel pyrosequencing: experiences and considerations for successful applications. Biotechniques 51: 167-177.
43. Buzon MJ, Codoner FM, Frost SD, Pou C, Puertas MC, et al. (2011) Deep molecular characterization of HIV-1 dynamics under suppressive HAART. PLoS Pathog 7: e1002314.
44. Rhee SY, Gonzales MJ, Kantor R, Betts BJ, Ravela J, et al. (2003) Human immunodeficiency virus reverse transcriptase and protease sequence database. Nucleic Acids Res 31: 298-303. (Pubitemid 36150389)
45. Shafer RW (2006) Rationale and uses of a public HIV drug-resistance database. J Infect Dis 194 Suppl 1: S51-58.
46. Van Rompay KK, Johnson JA, Blackwood EJ, Singh RP, Lipscomb J, et al. (2007) Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. Retrovirology 4: 25.
47. Shao W, Kearney M, Maldarelli F, Mellors JW, Stephens RM, et al. (2009) RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy. Retrovirology 6: 101.
48. Deere JD, Higgins J, Cannavo E, Villalobos A, Adamson L, et al. (2010) Viral decay kinetics in the highly active antiretroviral therapy-treated rhesus macaque model of AIDS. PLoS One 5: e11640.
49. Johnson VA, Calvez V, Gunthard HF, Paredes R, Pillay D, et al. (2011) 2011 update of the drug resistance mutations in HIV-1. Top Antivir Med 19: 156-164.
50. Kieffer TL, Finucane MM, Nettles RE, Quinn TC, Broman KW, et al. (2004) 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 189: 1452-1465. (Pubitemid 38543595)
51. Hermankova M, Ray SC, Ruff C, Powell-Davis M, Ingersoll R, et al. (2001) HIV-1 drug resistance profiles in children and adults with viral load of <50 copies/ml receiving combination therapy. JAMA 286: 196-207. (Pubitemid 32640851)
52. Persaud D, Siberry GK, Ahonkhai A, Kajdas J, Monie D, et al. (2004) Continued production of drug-sensitive human immunodeficiency virus type 1 in children on combination antiretroviral therapy who have undetectable viral loads. J Virol 78: 968-979. (Pubitemid 38067618)
53. 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.
54. Hatano H, Strain MC, Scherzer R, Bacchetti P, Wentworth D, et al. (2013) 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. Journal of Infectious Diseases 208: 1436-1442.
55. Nottet HS, van Dijk SJ, Fanoy EB, Goedegebuure IW, de Jong D, et al. (2009) HIV-1 can persist in aged memory CD4+ T lymphocytes with minimal signs of evolution after 8.3 years of effective highly active antiretroviral therapy. J Acquir Immune Defic Syndr 50: 345-353.
56. Evering TH, Mehandru S, Racz P, Tenner-Racz K, Poles MA, et al. (2012) Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection. PLoS Pathog 8: e1002506.
57. Josefsson L, von Stockenstrom S, Faria NR, Sinclair E, Bacchetti P, et al. (2013) The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time. Proc Natl Acad Sci U S A 110: E4987-4996.
58. Lee GQ, Swenson LC, Poon AF, Martin JN, Hatano H, et al. (2012) Prolonged and substantial discordance in prevalence of raltegravir-resistant HIV-1 in plasma versus PBMC samples revealed by 454 "deep" sequencing. PLoS One 7: e46181.
59. 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.
60. 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.
61. Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, et al. (2009) HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 15: 893-900.
62. Apetrei C, Pandrea I, Mellors JW (2012) Nonhuman primate models for HIV cure research. PLoS Pathog 8: e1002892.
63. Grant CK, DeBoer DJ, Essex M, Worley MB, Higgins J (1977) Antibodies from healthy cats exposed to feline leukemia virus lyse feline lymphoma cells slowly with cat complement. J Immunol 119: 401-406. (Pubitemid 8161567)
64. Van Rompay KKA, Babusis D, Abbott Z, Geng YZ, Jayashankar K, et al. (2012) Compared to Subcutaneous Tenofovir, Oral Tenofovir Disoproxyl Fumarate Administration Preferentially Concentrates the Drug into Gut-Associated Lymphoid Cells in Simian Immunodeficiency Virus-Infected Macaques. Antimicrobial Agents and Chemotherapy 56: 4980-4984.
65. Ljungdahlstahle E, Guzenda E, Bottiger D, Wahren B, Oberg B, et al. (1992) Penetration of Zidovudine and 3′-Fluoro-3′-Deoxythymidine into the Brain, Muscle-Tissue, and Veins in Cynomolgus Monkeys - Relation to Antiviral Action. Antimicrobial Agents and Chemotherapy 36: 2418-2422.
66. Garcia-Lerma JG, Otten RA, Qari SH, Jackson E, Cong ME, et al. (2008) Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. Plos Medicine 5: 291-299.
67. Leutenegger CM, Higgins J, Matthews TB, Tarantal AF, Luciw PA, et al. (2001) Real-time TaqMan PCR as a specific and more sensitive alternative to the branched-chain DNA assay for quantitation of simian immunodeficiency virus RNA. AIDS Res Hum Retroviruses 17: 243-251. (Pubitemid 32113572)
68. Daigle D SB, Pochart P. (2011) High-throughput sequencing of PCR products tagged with universal primers using 454 life sciences systems. Curr Protoc Mol Biol.
69. Shao W, Boltz VF, Spindler JE, Kearney MF, Maldarelli F, et al. (2013) Analysis of 454 sequencing error rate, error sources, and artifact recombination for detection of Low-frequency drug resistance mutations in HIV-1 DNA. Retrovirology 10: 18.
70. Judo MS, Wedel AB, Wilson C (1998) Stimulation and suppression of PCR-mediated recombination. Nucleic Acids Res 26: 1819-1825. (Pubitemid 28291822)
71. Wu JY, Jiang XT, Jiang YX, Lu SY, Zou F, et al. (2010) Effects of polymerase, template dilution and cycle number on PCR based 16 S rRNA diversity analysis using the deep sequencing method. BMC Microbiol 10: 255.
72. Odelberg SJ, Weiss RB, Hata A, White R (1995) Template-switching during DNA synthesis by Thermus aquaticus DNA polymerase I. Nucleic Acids Res 23: 2049-2057.
73. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, et al. (2011) MEGA5: Molecular Evolutionary Genetics Analysis Using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods. Molecular Biology and Evolution 28: 2731-2739.
74. Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32: 1792-1797.
75. Saitou N, Nei M (1987) The Neighbor-Joining Method - a New Method for Reconstructing Phylogenetic Trees. Molecular Biology and Evolution 4: 406- 425.
76. Tamura K, Nei M (1993) Estimation of the Number of Nucleotide Substitutions in the Control Region of Mitochondrial-DNA in Humans and Chimpanzees. Molecular Biology and Evolution 10: 512-526. (Pubitemid 23157236)
77. Rose PP, Korber BT (2000) Detecting hypermutations in viral sequences with an emphasis on G -> A hypermutation. Bioinformatics 16: 400-401. (Pubitemid 30417085)
78. Felsenstein J (1985) Confidence-Limits on Phylogenies - an Approach Using the Bootstrap. Evolution 39: 783-791.