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Published in: AIDS Research and Therapy 1/2011

Open Access 01-12-2011 | Research

Rebound of residual plasma viremia after initial decrease following addition of intravenous immunoglobulin to effective antiretroviral treatment of HIV

Authors: Tomas Mellberg, Veronica D Gonzalez, Annica Lindkvist, Arvid Edén, Anders Sönnerborg, Johan K Sandberg, Bo Svennerholm, Magnus Gisslén

Published in: AIDS Research and Therapy | Issue 1/2011

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Abstract

Background

High dosage of intravenous immunoglobulin (IVIG) has been observed as a possible activator of HIV gene expression in latently infected resting CD4+ T-cells, leading to a substantial decrease in both the reservoir and the residual plasma viremia when added to effective ART. IVIG treatment has also been reported to expand T regulatory cells (Tregs). The aim of this study was to evaluate possible long-term effect of IVIG treatment on residual viremia and T-lymphocyte activation.

Methods

Nine HIV-infected subjects on effective ART included in a previously reported study on IVIG treatment were evaluated 48-104 weeks after therapy. In addition, 14 HIV-infected controls on suppressive ART were included. HIV-1 RNA was analyzed in cell-free plasma by using an ultrasensitive PCR-method with a detection limit of 2 copies/mL. T-lymphocyte activation markers and serum interleukins were measured.

Results

Plasma residual viremia rebounded to pre-treatment levels, 48-104 weeks after the initial decrease that was observed following treatment with high-dosage IVIG. No long-term effect was observed regarding T-lymphocyte activation markers, T-regulatory cells or serum interleukins. In a post-hoc analysis, a correlation between plasma HIV-1-RNA and CD4+ T-cell count was found in both IVIG-treated patients and controls.

Conclusions

These results indicate that the decrease in the latent HIV-1 pool observed during IVIG treatment is transient. Although not our primary objective, we found a correlation between HIV-1 RNA and CD4+ T-cell count suggesting the possibility that patients with a higher CD4+ T-cell count might harbor a larger residual pool of latently infected CD4+ T-cells.
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Literature
1.
go back to reference Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF: Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med. 2003, 9: 727-728. 10.1038/nm880CrossRefPubMed Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF: Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med. 2003, 9: 727-728. 10.1038/nm880CrossRefPubMed
2.
go back to reference Lindkvist A, Eden A, Norstrom MM, Gonzalez VD, Nilsson S, Svennerholm B, Karlsson AC, Sandberg JK, Sonnerborg A, Gisslen M: Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study. AIDS Res Ther. 2009, 6: 15- 10.1186/1742-6405-6-15PubMedCentralCrossRefPubMed Lindkvist A, Eden A, Norstrom MM, Gonzalez VD, Nilsson S, Svennerholm B, Karlsson AC, Sandberg JK, Sonnerborg A, Gisslen M: Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study. AIDS Res Ther. 2009, 6: 15- 10.1186/1742-6405-6-15PubMedCentralCrossRefPubMed
3.
go back to reference Gisslen M, Fredman P, Fuchs D, Lekman A, Rosengren L: Temporarily controlled HIV-1 replication after intravenous immunoglobulin treatment of Guillain-Barre syndrome. Scand J Infect Dis. 2005, 37: 877-881. 10.1080/00365540500277227CrossRefPubMed Gisslen M, Fredman P, Fuchs D, Lekman A, Rosengren L: Temporarily controlled HIV-1 replication after intravenous immunoglobulin treatment of Guillain-Barre syndrome. Scand J Infect Dis. 2005, 37: 877-881. 10.1080/00365540500277227CrossRefPubMed
4.
go back to reference Yilmaz A, Svennerholm B, Hagberg L, Gisslen M: Cerebrospinal fluid viral loads reach less than 2 copies/ml in HIV-1-infected patients with effective antiretroviral therapy. Antivir Ther. 2006, 11: 833-837.PubMed Yilmaz A, Svennerholm B, Hagberg L, Gisslen M: Cerebrospinal fluid viral loads reach less than 2 copies/ml in HIV-1-infected patients with effective antiretroviral therapy. Antivir Ther. 2006, 11: 833-837.PubMed
5.
go back to reference Gonzalez VD, Bjorkstrom NK, Malmberg KJ, Moll M, Kuylenstierna C, Michaelsson J, Ljunggren HG, Sandberg JK: Application of nine-color flow cytometry for detailed studies of the phenotypic complexity and functional heterogeneity of human lymphocyte subsets. J Immunol Methods. 2008, 330: 64-74. 10.1016/j.jim.2007.10.020PubMedCentralCrossRefPubMed Gonzalez VD, Bjorkstrom NK, Malmberg KJ, Moll M, Kuylenstierna C, Michaelsson J, Ljunggren HG, Sandberg JK: Application of nine-color flow cytometry for detailed studies of the phenotypic complexity and functional heterogeneity of human lymphocyte subsets. J Immunol Methods. 2008, 330: 64-74. 10.1016/j.jim.2007.10.020PubMedCentralCrossRefPubMed
6.
go back to reference Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, Chadwick K, Margolick J, Quinn TC, Huo YH, Brookmeyer R, Zeiger MA, Barditch-Crovo P, Sikiciano RF: Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature. 1997, 387: 183-188. 10.1038/387183a0CrossRefPubMed Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, Chadwick K, Margolick J, Quinn TC, Huo YH, Brookmeyer R, Zeiger MA, Barditch-Crovo P, Sikiciano RF: Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature. 1997, 387: 183-188. 10.1038/387183a0CrossRefPubMed
7.
go back to reference Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS: Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci USA. 1997, 94: 13193-13197. 10.1073/pnas.94.24.13193PubMedCentralCrossRefPubMed Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS: Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci USA. 1997, 94: 13193-13197. 10.1073/pnas.94.24.13193PubMedCentralCrossRefPubMed
8.
go back to reference Palmer S, Maldarelli F, Wiegand A, Bernstein B, Hanna GJ, Brun SC, Kempf DJ, Mellors JW, Coffin JM, King MS: Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci USA. 2008, 105: 3879-3884. 10.1073/pnas.0800050105PubMedCentralCrossRefPubMed Palmer S, Maldarelli F, Wiegand A, Bernstein B, Hanna GJ, Brun SC, Kempf DJ, Mellors JW, Coffin JM, King MS: Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci USA. 2008, 105: 3879-3884. 10.1073/pnas.0800050105PubMedCentralCrossRefPubMed
9.
go back to reference Dinoso JB, Kim SY, Wiegand AM, Palmer SE, Gange SJ, Cranmer L, O'Shea A, Callender M, Spivak A, Brennan T, Kearney MF, Proschan MA, Michan JM, Rehm CA, Coffin JM, Mellors JW, Siliciano RF, Maldarelli F: Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci USA. 2009, 106: 9403-9408. 10.1073/pnas.0903107106PubMedCentralCrossRefPubMed Dinoso JB, Kim SY, Wiegand AM, Palmer SE, Gange SJ, Cranmer L, O'Shea A, Callender M, Spivak A, Brennan T, Kearney MF, Proschan MA, Michan JM, Rehm CA, Coffin JM, Mellors JW, Siliciano RF, Maldarelli F: Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci USA. 2009, 106: 9403-9408. 10.1073/pnas.0903107106PubMedCentralCrossRefPubMed
10.
go back to reference McMahon D, Jones J, Wiegand A, Gange SJ, Kearney M, Palmer S, McNulty S, Metcalf JA, Acosta E, Rehm C, Coffin JM, Melloes JW, Maldarelli F: 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. 2010, 50: 912-919. 10.1086/650749PubMedCentralCrossRefPubMed McMahon D, Jones J, Wiegand A, Gange SJ, Kearney M, Palmer S, McNulty S, Metcalf JA, Acosta E, Rehm C, Coffin JM, Melloes JW, Maldarelli F: 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. 2010, 50: 912-919. 10.1086/650749PubMedCentralCrossRefPubMed
11.
go back to reference Archin NM, Cheema M, Parker D, Wiegand A, Bosch RJ, Coffin JM, Eron J, Cohen M, Margolis DM: Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection. PLoS One. 2010, 5: e9390- 10.1371/journal.pone.0009390PubMedCentralCrossRefPubMed Archin NM, Cheema M, Parker D, Wiegand A, Bosch RJ, Coffin JM, Eron J, Cohen M, Margolis DM: Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection. PLoS One. 2010, 5: e9390- 10.1371/journal.pone.0009390PubMedCentralCrossRefPubMed
12.
go back to reference Bayry J, Thirion M, Misra N, Thorenoor N, Delignat S, Lacroix-Desmazes S, Bellon B, Kaveri S, Kazatchkine MD: Mechanisms of action of intravenous immunoglobulin in autoimmune and inflammatory diseases. Neurol Sci. 2003, 24 (Suppl 4): S217-221.CrossRefPubMed Bayry J, Thirion M, Misra N, Thorenoor N, Delignat S, Lacroix-Desmazes S, Bellon B, Kaveri S, Kazatchkine MD: Mechanisms of action of intravenous immunoglobulin in autoimmune and inflammatory diseases. Neurol Sci. 2003, 24 (Suppl 4): S217-221.CrossRefPubMed
13.
go back to reference Negi VS, Elluru S, Siberil S, Graff-Dubois S, Mouthon L, Kazatchkine MD, Lacroix-Desmazes S, Bayry J, Kaveri SV: Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. J Clin Immunol. 2007, 27: 233-245. 10.1007/s10875-007-9088-9CrossRefPubMed Negi VS, Elluru S, Siberil S, Graff-Dubois S, Mouthon L, Kazatchkine MD, Lacroix-Desmazes S, Bayry J, Kaveri SV: Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. J Clin Immunol. 2007, 27: 233-245. 10.1007/s10875-007-9088-9CrossRefPubMed
14.
go back to reference Rhoades CJ, Williams MA, Kelsey SM, Newland AC: Monocyte-macrophage system as targets for immunomodulation by intravenous immunoglobulin. Blood Rev. 2000, 14: 14-30. 10.1054/blre.1999.0121CrossRefPubMed Rhoades CJ, Williams MA, Kelsey SM, Newland AC: Monocyte-macrophage system as targets for immunomodulation by intravenous immunoglobulin. Blood Rev. 2000, 14: 14-30. 10.1054/blre.1999.0121CrossRefPubMed
15.
go back to reference Brooks DG, Hamer DH, Arlen PA, Gao L, Bristol G, Kitchen CM, Berger EA, Zack JA: Molecular characterization, reactivation, and depletion of latent HIV. Immunity. 2003, 19: 413-423. 10.1016/S1074-7613(03)00236-XCrossRefPubMed Brooks DG, Hamer DH, Arlen PA, Gao L, Bristol G, Kitchen CM, Berger EA, Zack JA: Molecular characterization, reactivation, and depletion of latent HIV. Immunity. 2003, 19: 413-423. 10.1016/S1074-7613(03)00236-XCrossRefPubMed
16.
go back to reference Wang FX, Xu Y, Sullivan J, Souder E, Argyris EG, Acheampong EA, Fisher J, Sierra M, Thomson MM, Najera R, Frank I, Kulkosky J, Pomerantz RJ, Nunnari G: 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. 2005, 115: 128-137.PubMedCentralCrossRefPubMed Wang FX, Xu Y, Sullivan J, Souder E, Argyris EG, Acheampong EA, Fisher J, Sierra M, Thomson MM, Najera R, Frank I, Kulkosky J, Pomerantz RJ, Nunnari G: 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. 2005, 115: 128-137.PubMedCentralCrossRefPubMed
17.
go back to reference Sereti I, Dunham RM, Spritzler J, Aga E, Proschan MA, Medvik K, Battaglia CA, Landay AL, Pahwa S, Fischl MA, Asmuth DM, Tenorio AR, Altman JD, Fox L, Moir S, Malaspina A, Morre M, Buffet R, Silvesri G, Lederman MM, : IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Blood. 2009, 113: 6304-6314. 10.1182/blood-2008-10-186601PubMedCentralCrossRefPubMed Sereti I, Dunham RM, Spritzler J, Aga E, Proschan MA, Medvik K, Battaglia CA, Landay AL, Pahwa S, Fischl MA, Asmuth DM, Tenorio AR, Altman JD, Fox L, Moir S, Malaspina A, Morre M, Buffet R, Silvesri G, Lederman MM, : IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Blood. 2009, 113: 6304-6314. 10.1182/blood-2008-10-186601PubMedCentralCrossRefPubMed
18.
go back to reference Maldarelli F, Palmer S, King MS, Wiegand A, Polis MA, Mican J, Kovacs JA, Davey RT, Rock-Kress D, Dewar R, Liu S, Metcalf JA, Rehm C, Brun SC, Hanna GJ, Kempf DJ, Coffin JM, Mellors JWl: ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 2007, 3: e46- 10.1371/journal.ppat.0030046PubMedCentralCrossRefPubMed Maldarelli F, Palmer S, King MS, Wiegand A, Polis MA, Mican J, Kovacs JA, Davey RT, Rock-Kress D, Dewar R, Liu S, Metcalf JA, Rehm C, Brun SC, Hanna GJ, Kempf DJ, Coffin JM, Mellors JWl: ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 2007, 3: e46- 10.1371/journal.ppat.0030046PubMedCentralCrossRefPubMed
19.
go back to reference Mavigner M, Delobel P, Cazabat M, Dubois M, L'Faqihi-Olive FE, Raymond S, Pasquier C, Marchou B, Massip P, Izopet J: HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. PLoS One. 2009, 4: e7658- 10.1371/journal.pone.0007658PubMedCentralCrossRefPubMed Mavigner M, Delobel P, Cazabat M, Dubois M, L'Faqihi-Olive FE, Raymond S, Pasquier C, Marchou B, Massip P, Izopet J: HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. PLoS One. 2009, 4: e7658- 10.1371/journal.pone.0007658PubMedCentralCrossRefPubMed
20.
go back to reference Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, Boucher G, Boulassel MR, Ghattas G, Brenchley JM, Schacker TW, Hill BJ, Douek DC, Routy JP, Haddad EK, Sekaly RP: HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009, 15: 893-900. 10.1038/nm.1972PubMedCentralCrossRefPubMed Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, Boucher G, Boulassel MR, Ghattas G, Brenchley JM, Schacker TW, Hill BJ, Douek DC, Routy JP, Haddad EK, Sekaly RP: HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009, 15: 893-900. 10.1038/nm.1972PubMedCentralCrossRefPubMed
Metadata
Title
Rebound of residual plasma viremia after initial decrease following addition of intravenous immunoglobulin to effective antiretroviral treatment of HIV
Authors
Tomas Mellberg
Veronica D Gonzalez
Annica Lindkvist
Arvid Edén
Anders Sönnerborg
Johan K Sandberg
Bo Svennerholm
Magnus Gisslén
Publication date
01-12-2011
Publisher
BioMed Central
Published in
AIDS Research and Therapy / Issue 1/2011
Electronic ISSN: 1742-6405
DOI
https://doi.org/10.1186/1742-6405-8-21

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