Limits on replenishment of the resting CD4+ T cell reservoir for HIV in patients on HAART

PLoS Pathogens

Volumn 3, Issue 8, 2007, Pages 1165-1174

  Sedaghat, Ahmad R ^a   Siliciano, Janet D ^a   Brennan, Timothy P ^a   Wilke, Claus O ^b   Siliciano, Robert F ^a,c  

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

^b UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^c HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRETROVIRUS AGENT; ZIDOVUDINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; RNA DIRECTED DNA POLYMERASE INHIBITOR;

ADULT; ARTICLE; CALCULATION; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; HALF LIFE TIME; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; LATENT PERIOD; MAJOR CLINICAL STUDY; MATHEMATICAL MODEL; MOLECULAR CLONING; MONOTHERAPY; VIREMIA; VIRUS REPLICATION; DRUG EFFECT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; PHYSIOLOGY; THEORETICAL MODEL; TIME; VIROLOGY; VIRUS LATENCY;

HUMAN IMMUNODEFICIENCY VIRUS 1;

ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CD4-POSITIVE T-LYMPHOCYTES; HIV INFECTIONS; HIV-1; HUMANS; MODELS, THEORETICAL; REVERSE TRANSCRIPTASE INHIBITORS; TIME FACTORS; VIRUS LATENCY; VIRUS REPLICATION;

EID: 34548424552     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.0030122     Document Type: Article

References (56)

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, et al. (2003) Longterm follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med 9: 727-728.
9. 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.
10. 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.
11. 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.
12. 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.
13. Frenkel LM, Wang Y, Learn GH, McKernan JL, Ellis GM, et al. (2003) Multiple viral genetic analyses detect low-level human immunodeficiency virus type 1 replication during effective highly active antiretroviral therapy. J Virol 77: 5721-5730.
14. Furtado MR, Callaway DS, Phair JP, Kunstman KJ, Stanton JL, et al. (1999) Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. N Engl J Med 340: 1614-1622.
15. Imamichi H, Crandall KA, Natarajan V, Jiang MK, Dewar RL, et al. (2001) Human immunodeficiency virus type 1 quasi species that rebound after discontinuation of highly active antiretroviral therapy are similar to the viral quasi species present before initiation of therapy. J Infect Dis 183: 36-50.
16. Natarajan V, Bosche M, Metcalf JA, Ward DJ, Lane HC, et al. (1999) HIV-1 replication in patients with undetectable plasma virus receiving HAART. Highly active antiretroviral therapy. Lancet 353: 119-120.
17. 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.
18. Ramratnam B, Ribeiro R, He T, Chung C, Simon V, et al. (2004) Intensification of antiretroviral therapy accelerates the decay of the HIV-1 latent reservoir and decreases, but does not eliminate, ongoing virus replication. J Acquir Immune Defic Syndr 35: 33-37.
19. 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.
20. 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.
21. 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.
22. Pomerantz RJ (2001) Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. Biomed Pharmacother 55: 7-15.
23. Schockmel GA, Yerly S, Perrin L (1997) Detection of low HIV-1 RNA levels in plasma. J Acquir Immune Defic Syndr Hum Retrovirol 14: 179-183.
24. 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.
25. Greub G, Cozzi-Lepri A, Ledergerber B, Staszewski S, Perrin L, et al. (2002) Intermittent and sustained low-level HIV viral rebound in patients receiving potent antiretroviral therapy. AIDS 16: 1967-1969.
26. 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.
27. Mira JA, Macias J, Nogales C, Fernandez-Rivera J, Garcia-Garcia JA, et al. (2002) Transient rebounds of low-level viraemia among HIV-infected patients under HAART are not associated with virological or immunological failure. Antivir Ther 7: 251-256.
28. Siliciano JD, Siliciano RF (2004) A long-term latent reservoir for HIV-1: Discovery and clinical implications. J Antimicrob Chemother 54: 6-9.
29. Hermankova M, Siliciano JD, Zhou Y, Monie D, Chadwick K, et al. (2003) Analysis of human immunodeficiency virus type 1 gene expression in latently infected resting CD4+ T lymphocytes in vivo. J Virol 77: 7383-7392.
30. Lassen KG, Bailey JR, Siliciano RF (2004) Analysis of human immunodeficiency virus type 1 transcriptional elongation in resting CD4+ T cells in vivo. J Virol 78: 9105-9114.
31. Ruff CT, Ray SC, Kwon P, Zinn R, Pendleton A, et al. (2002) Persistence of wild-type virus and lack of temporal structure in the latent reservoir for human immunodeficiency virus type 1 in pediatric patients with extensive antiretroviral exposure. J Virol 76: 9481-9492.
32. Deeks SG, Hoh R, Grant RM, Wrin T, Barbour JD, et al. (2002) 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 185: 315-323.
33. Hellerstein MK, McCune JM (1997) T cell turnover in HIV-1 disease. Immunity 7: 583-589.
34. Hellerstein MK, Hoh RA, Hanley MB, Cesar D, Lee D, et al. (2003) Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection. J Clin Invest 112: 956-966.
35. Neese RA, Misell LM, Turner S, Chu A, Kim J, et al. (2002) Measurement in vivo of proliferation rates of slow turnover cells by 2H2O labeling of the deoxyribose moiety of DNA. Proc Natl Acad Sci U S A 99: 15345-15350.
36. Bonhoeffer S, May RM, Shaw GM, Nowak MA (1997) Virus dynamics and drug therapy. Proc Natl Acad Sci U S A 94: 6971-6976.
37. Bonhoeffer S, Coffin JM, Nowak MA (1997) Human immunodeficiency virus drug therapy and virus load. J Virol 71: 3275-3278.
38. De Boer RJ, Perelson AS (1998) Target cell limited and immune control models of HIV infection: a comparison. J Theor Biol 190: 201-214.
39. Grossman Z, Meier-Schellersheim M, Sousa AE, Victorino RM, Paul WE (2002) CD4+ T-cell depletion in HIV infection: Are we closer to understanding the cause? Nat Med 8: 319-323.
40. Nowak MA, Bonhoeffer S, Shaw GM, May RM (1997) Anti-viral drug treatment: Dynamics of resistance in free virus and infected cell populations. J Theor Biol 184: 203-217.
41. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD (1996) HIV-1 dynamics in vivo: Virion clearance rate, infected cell life-span, and viral generation time. Science 271: 1582-1586.
42. Perelson AS, Essunger P, Ho DD (1997) Dynamics of HIV-1 and CD4+ lymphocytes in vivo. AIDS 11 Suppl A: S17-S24.
43. Phillips AN (1996) Reduction of HIV concentration during acute infection: Independence from a specific immune response. Science 271: 497-499.
44. Wodarz D, Nowak MA (2002) Mathematical models of HIV pathogenesis and treatment. Bioessays 24: 1178-1187.
45. 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.
46. Nettles RE, Kieffer TL, Kwon P, Monie D, Han Y, et al. (2005) Intermittent HIV-1 viremia (Blips) and drug resistance in patients receiving HAART. JAMA 293: 817-829.
47. 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.
48. Mohri H, Perelson AS, Tung K, Ribeiro RM, Ramratnam B, et al. (2001) Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J Exp Med 194: 1277-1287.
49. Ribeiro RM, Mohri H, Ho DD, Perelson AS (2002) In vivo dynamics of T cell activation, proliferation, and death in HIV-1 infection: Why are CD4+ but not CD8+ T cells depleted? Proc Natl Acad Sci U S A 99: 15572-15577.
50. Ewens WJ, Grant G (2001) Statistical methods in bioinformatics an introduction. New York: Springer. 476 p.
51. Orlitsky A, Santhanam NP, Zhang J (2003) Always Good Turing: Asymptotically optimal probability estimation. Science 302: 427-431.
52. Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, et al. (1999) Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med 340: 1605-1613.
53. Simmons R, Siliciano RF (2004) Can antiretroviral therapy ever be stopped? An update. AIDS Read 14: 435-2.
54. Barbaro G (2006) Highly active antiretroviral therapy-associated metabolic syndrome: Pathogenesis and cardiovascular risk. Am J Ther 13: 248-260.
55. Manchanda T, Schiedel D, Fischer D, Dekaban GA, Rieder MJ (2002) Adverse drug reactions to protease inhibitors. Can J Clin Pharmacol 9: 137-146.
56. Deeks SG (2006) The risk of treatment versus the risk of HIV replication. Lancet 367: 1955-1956.