Pilot Trial of the Effect of Vorinostat and AGS-004 on Persistent HIV-1 Infection

Summary

The purpose of this research study is to 1) evaluate the safety of a series of injections with the AGS-004 product in combination with a series of Vorinostat doses and 2) to help scientists evaluate ways of reactivating latent (non-acting) HIV virus and determine if the immune system can be made stronger to eliminate the activated HIV virus.

Timeline

Start

2016-03

Primary completion

2018-07-11

Completion

2018-07-11

Publications

• Background Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, Margolick J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman DD, Siliciano RF. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997 Nov 14;278(5341):1295-300. doi: 10.1126/science.278.5341.1295.
• Background Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, Smith K, Lisziewicz J, Lori F, Flexner C, Quinn TC, Chaisson RE, Rosenberg E, Walker B, Gange S, Gallant J, Siliciano RF. 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 May;5(5):512-7. doi: 10.1038/8394.
• Background 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 U S A. 1997 Nov 25;94(24):13193-7. doi: 10.1073/pnas.94.24.13193.
• Background Gay CL, DeBenedette MA, Tcherepanova IY, Gamble A, Lewis WE, Cope AB, Kuruc JD, McGee KS, Kearney MF, Coffin JM, Archin NM, Hicks CB, Eron JJ, Nicolette CA, Margolis DM. Immunogenicity of AGS-004 Dendritic Cell Therapy in Patients Treated During Acute HIV Infection. AIDS Res Hum Retroviruses. 2018 Jan;34(1):111-122. doi: 10.1089/aid.2017.0071. Epub 2017 Jun 21.
• Background Coull JJ, Romerio F, Sun JM, Volker JL, Galvin KM, Davie JR, Shi Y, Hansen U, Margolis DM. The human factors YY1 and LSF repress the human immunodeficiency virus type 1 long terminal repeat via recruitment of histone deacetylase 1. J Virol. 2000 Aug;74(15):6790-9. doi: 10.1128/jvi.74.15.6790-6799.2000.
• Background Romerio F, Gabriel MN, Margolis DM. Repression of human immunodeficiency virus type 1 through the novel cooperation of human factors YY1 and LSF. J Virol. 1997 Dec;71(12):9375-82. doi: 10.1128/JVI.71.12.9375-9382.1997.
• Background He G, Margolis DM. Counterregulation of chromatin deacetylation and histone deacetylase occupancy at the integrated promoter of human immunodeficiency virus type 1 (HIV-1) by the HIV-1 repressor YY1 and HIV-1 activator Tat. Mol Cell Biol. 2002 May;22(9):2965-73. doi: 10.1128/MCB.22.9.2965-2973.2002.
• Background Coull JJ, He G, Melander C, Rucker VC, Dervan PB, Margolis DM. Targeted derepression of the human immunodeficiency virus type 1 long terminal repeat by pyrrole-imidazole polyamides. J Virol. 2002 Dec;76(23):12349-54. doi: 10.1128/jvi.76.23.12349-12354.2002.
• Background Ylisastigui L, Coull JJ, Rucker VC, Melander C, Bosch RJ, Brodie SJ, Corey L, Sodora DL, Dervan PB, Margolis DM. Polyamides reveal a role for repression in latency within resting T cells of HIV-infected donors. J Infect Dis. 2004 Oct 15;190(8):1429-37. doi: 10.1086/423822. Epub 2004 Sep 15.
• Background 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 May 21;18(8):1101-8. doi: 10.1097/00002030-200405210-00003.
• Background Marban C, Suzanne S, Dequiedt F, de Walque S, Redel L, Van Lint C, Aunis D, Rohr O. Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing. EMBO J. 2007 Jan 24;26(2):412-23. doi: 10.1038/sj.emboj.7601516.
• Background Williams SA, Chen LF, Kwon H, Ruiz-Jarabo CM, Verdin E, Greene WC. NF-kappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J. 2006 Jan 11;25(1):139-49. doi: 10.1038/sj.emboj.7600900. Epub 2005 Dec 1.
• Background Imai K, Okamoto T. Transcriptional repression of human immunodeficiency virus type 1 by AP-4. J Biol Chem. 2006 May 5;281(18):12495-505. doi: 10.1074/jbc.M511773200. Epub 2006 Mar 15.
• Background Jiang G, Espeseth A, Hazuda DJ, Margolis DM. c-Myc and Sp1 contribute to proviral latency by recruiting histone deacetylase 1 to the human immunodeficiency virus type 1 promoter. J Virol. 2007 Oct;81(20):10914-23. doi: 10.1128/JVI.01208-07. Epub 2007 Aug 1.
• Background du Chene I, Basyuk E, Lin YL, Triboulet R, Knezevich A, Chable-Bessia C, Mettling C, Baillat V, Reynes J, Corbeau P, Bertrand E, Marcello A, Emiliani S, Kiernan R, Benkirane M. Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency. EMBO J. 2007 Jan 24;26(2):424-35. doi: 10.1038/sj.emboj.7601517.
• Background Tyagi M, Karn J. CBF-1 promotes transcriptional silencing during the establishment of HIV-1 latency. EMBO J. 2007 Dec 12;26(24):4985-95. doi: 10.1038/sj.emboj.7601928. Epub 2007 Nov 15.
• Background Lehrman G, Hogue IB, Palmer S, Jennings C, Spina CA, Wiegand A, Landay AL, Coombs RW, Richman DD, Mellors JW, Coffin JM, Bosch RJ, Margolis DM. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet. 2005 Aug 13-19;366(9485):549-55. doi: 10.1016/S0140-6736(05)67098-5.
• Background Siliciano JD, Lai J, Callender M, Pitt E, Zhang H, Margolick JB, Gallant JE, Cofrancesco J Jr, Moore RD, Gange SJ, Siliciano RF. Stability of the latent reservoir for HIV-1 in patients receiving valproic acid. J Infect Dis. 2007 Mar 15;195(6):833-6. doi: 10.1086/511823. Epub 2007 Jan 30.
• Background Archin NM, Eron JJ, Palmer S, Hartmann-Duff A, Martinson JA, Wiegand A, Bandarenko N, Schmitz JL, Bosch RJ, Landay AL, Coffin JM, Margolis DM. Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells. AIDS. 2008 Jun 19;22(10):1131-5. doi: 10.1097/QAD.0b013e3282fd6df4.
• Background Sagot-Lerolle N, Lamine A, Chaix ML, Boufassa F, Aboulker JP, Costagliola D, Goujard C, Pallier C, Delfraissy JF, Lambotte O; ANRS EP39 study. Prolonged valproic acid treatment does not reduce the size of latent HIV reservoir. AIDS. 2008 Jun 19;22(10):1125-9. doi: 10.1097/QAD.0b013e3282fd6ddc.
• Background 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 Feb 23;5(2):e9390. doi: 10.1371/journal.pone.0009390.
• Background Archin NM, Espeseth A, Parker D, Cheema M, Hazuda D, Margolis DM. Expression of latent HIV induced by the potent HDAC inhibitor suberoylanilide hydroxamic acid. AIDS Res Hum Retroviruses. 2009 Feb;25(2):207-12. doi: 10.1089/aid.2008.0191.
• Background Contreras X, Schweneker M, Chen CS, McCune JM, Deeks SG, Martin J, Peterlin BM. Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells. J Biol Chem. 2009 Mar 13;284(11):6782-9. doi: 10.1074/jbc.M807898200. Epub 2009 Jan 9.
• Background Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, Chadwick K, Margolick J, Quinn TC, Kuo YH, Brookmeyer R, Zeiger MA, Barditch-Crovo P, Siliciano RF. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature. 1997 May 8;387(6629):183-8. doi: 10.1038/387183a0.
• Background Archin NM, Bateson R, Tripathy MK, Crooks AM, Yang KH, Dahl NP, Kearney MF, Anderson EM, Coffin JM, Strain MC, Richman DD, Robertson KR, Kashuba AD, Bosch RJ, Hazuda DJ, Kuruc JD, Eron JJ, Margolis DM. HIV-1 expression within resting CD4+ T cells after multiple doses of vorinostat. J Infect Dis. 2014 Sep 1;210(5):728-35. doi: 10.1093/infdis/jiu155. Epub 2014 Mar 11.
• Background Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, Parker DC, Anderson EM, Kearney MF, Strain MC, Richman DD, Hudgens MG, Bosch RJ, Coffin JM, Eron JJ, Hazuda DJ, Margolis DM. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature. 2012 Jul 25;487(7408):482-5. doi: 10.1038/nature11286.
• Background Kelly WK, O'Connor OA, Krug LM, Chiao JH, Heaney M, Curley T, MacGregore-Cortelli B, Tong W, Secrist JP, Schwartz L, Richardson S, Chu E, Olgac S, Marks PA, Scher H, Richon VM. Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J Clin Oncol. 2005 Jun 10;23(17):3923-31. doi: 10.1200/JCO.2005.14.167. Epub 2005 May 16.
• Background Archin NM, Keedy KS, Espeseth A, Dang H, Hazuda DJ, Margolis DM. Expression of latent human immunodeficiency type 1 is induced by novel and selective histone deacetylase inhibitors. AIDS. 2009 Sep 10;23(14):1799-806. doi: 10.1097/QAD.0b013e32832ec1dc.
• Background Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang HC, Zhang H, Margolick JB, Blankson JN, Siliciano RF. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity. 2012 Mar 23;36(3):491-501. doi: 10.1016/j.immuni.2012.01.014. Epub 2012 Mar 8.
• Background DeBenedette MA, Calderhead DM, Ketteringham H, Gamble AH, Horvatinovich JM, Tcherepanova IY, Nicolette CA, Healey DG. Priming of a novel subset of CD28+ rapidly expanding high-avidity effector memory CTL by post maturation electroporation-CD40L dendritic cells is IL-12 dependent. J Immunol. 2008 Oct 15;181(8):5296-305. doi: 10.4049/jimmunol.181.8.5296.
• Background Calderhead DM, DeBenedette MA, Ketteringham H, Gamble AH, Horvatinovich JM, Tcherepanova IY, Nicolette CA, Healey DG. Cytokine maturation followed by CD40L mRNA electroporation results in a clinically relevant dendritic cell product capable of inducing a potent proinflammatory CTL response. J Immunother. 2008 Oct;31(8):731-41. doi: 10.1097/CJI.0b013e318183db02.
• Background Tcherepanova I, Harris J, Starr A, Cleveland J, Ketteringham H, Calderhead D, Horvatinovich J, Healey D, Nicolette CA. Multiplex RT-PCR amplification of HIV genes to create a completely autologous DC-based immunotherapy for the treatment of HIV infection. PLoS One. 2008 Jan 30;3(1):e1489. doi: 10.1371/journal.pone.0001489.
• Background Addo MM, Yu XG, Rosenberg ES, Walker BD, Altfeld M. Cytotoxic T-lymphocyte (CTL) responses directed against regulatory and accessory proteins in HIV-1 infection. DNA Cell Biol. 2002 Sep;21(9):671-8. doi: 10.1089/104454902760330219.
• Background Van Gulck ER, Ponsaerts P, Heyndrickx L, Vereecken K, Moerman F, De Roo A, Colebunders R, Van den Bosch G, Van Bockstaele DR, Van Tendeloo VF, Allard S, Verrier B, Maranon C, Hoeffel G, Hosmalin A, Berneman ZN, Vanham G. Efficient stimulation of HIV-1-specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins. Blood. 2006 Mar 1;107(5):1818-27. doi: 10.1182/blood-2005-01-0339. Epub 2005 Nov 1.
• Background Altfeld M, Addo MM, Eldridge RL, Yu XG, Thomas S, Khatri A, Strick D, Phillips MN, Cohen GB, Islam SA, Kalams SA, Brander C, Goulder PJ, Rosenberg ES, Walker BD; HIV Study Collaboration. Vpr is preferentially targeted by CTL during HIV-1 infection. J Immunol. 2001 Sep 1;167(5):2743-52. doi: 10.4049/jimmunol.167.5.2743.
• Background Novitsky V, Cao H, Rybak N, Gilbert P, McLane MF, Gaolekwe S, Peter T, Thior I, Ndung'u T, Marlink R, Lee TH, Essex M. Magnitude and frequency of cytotoxic T-lymphocyte responses: identification of immunodominant regions of human immunodeficiency virus type 1 subtype C. J Virol. 2002 Oct;76(20):10155-68. doi: 10.1128/jvi.76.20.10155-10168.2002.
• Background Quaranta MG, Mattioli B, Giordani L, Viora M. The immunoregulatory effects of HIV-1 Nef on dendritic cells and the pathogenesis of AIDS. FASEB J. 2006 Nov;20(13):2198-208. doi: 10.1096/fj.06-6260rev.
• Background Majumder B, Janket ML, Schafer EA, Schaubert K, Huang XL, Kan-Mitchell J, Rinaldo CR Jr, Ayyavoo V. Human immunodeficiency virus type 1 Vpr impairs dendritic cell maturation and T-cell activation: implications for viral immune escape. J Virol. 2005 Jul;79(13):7990-8003. doi: 10.1128/JVI.79.13.7990-8003.2005.
• Background Tcherepanova I, Starr A, Lackford B, Adams MD, Routy JP, Boulassel MR, Calderhead D, Healey D, Nicolette C. The immunosuppressive properties of the HIV Vpr protein are linked to a single highly conserved residue, R90. PLoS One. 2009 Jun 10;4(6):e5853. doi: 10.1371/journal.pone.0005853.
• Background Routy JP, Boulassel MR, Yassine-Diab B, Nicolette C, Healey D, Jain R, Landry C, Yegorov O, Tcherepanova I, Monesmith T, Finke L, Sekaly RP. Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy. Clin Immunol. 2010 Feb;134(2):140-7. doi: 10.1016/j.clim.2009.09.009. Epub 2009 Nov 4.
• Background Jones RB, O'Connor R, Mueller S, Foley M, Szeto GL, Karel D, Lichterfeld M, Kovacs C, Ostrowski MA, Trocha A, Irvine DJ, Walker BD. Histone deacetylase inhibitors impair the elimination of HIV-infected cells by cytotoxic T-lymphocytes. PLoS Pathog. 2014 Aug 14;10(8):e1004287. doi: 10.1371/journal.ppat.1004287. eCollection 2014 Aug.
• Background Rasmussen TA, Schmeltz Sogaard O, Brinkmann C, Wightman F, Lewin SR, Melchjorsen J, Dinarello C, Ostergaard L, Tolstrup M. Comparison of HDAC inhibitors in clinical development: effect on HIV production in latently infected cells and T-cell activation. Hum Vaccin Immunother. 2013 May;9(5):993-1001. doi: 10.4161/hv.23800. Epub 2013 Jan 31.
• Background Elliott JH, Wightman F, Solomon A, Ghneim K, Ahlers J, Cameron MJ, Smith MZ, Spelman T, McMahon J, Velayudham P, Brown G, Roney J, Watson J, Prince MH, Hoy JF, Chomont N, Fromentin R, Procopio FA, Zeidan J, Palmer S, Odevall L, Johnstone RW, Martin BP, Sinclair E, Deeks SG, Hazuda DJ, Cameron PU, Sekaly RP, Lewin SR. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog. 2014 Nov 13;10(10):e1004473. doi: 10.1371/journal.ppat.1004473. eCollection 2014 Oct.
• Background Sogaard O, Graversen ME, Leth S, Brinkmann C, Kjaer AS, Olesen R, et al. The HDAC inhibitor romidepsin is safe and effectively reverses HIV-1 latency in vivo as measured by standard clinical assays. In: 20th International AIDS Conference. Melbourne, Australia; 2014.
• Background Wei DG, Chiang V, Fyne E, Balakrishnan M, Barnes T, Graupe M, Hesselgesser J, Irrinki A, Murry JP, Stepan G, Stray KM, Tsai A, Yu H, Spindler J, Kearney M, Spina CA, McMahon D, Lalezari J, Sloan D, Mellors J, Geleziunas R, Cihlar T. Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells from patients on suppressive antiretroviral therapy at concentrations achieved by clinical dosing. PLoS Pathog. 2014 Apr 10;10(4):e1004071. doi: 10.1371/journal.ppat.1004071. eCollection 2014 Apr.
• Background Cillo AR, Krishnan S, McMahon DK, Mitsuyasu RT, Para MF, Mellors JW. Impact of chemotherapy for HIV-1 related lymphoma on residual viremia and cellular HIV-1 DNA in patients on suppressive antiretroviral therapy. PLoS One. 2014 Mar 17;9(3):e92118. doi: 10.1371/journal.pone.0092118. eCollection 2014.
• Background 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 Apr;20(4):425-9. doi: 10.1038/nm.3489. Epub 2014 Mar 23.
• Background Debenedette M, Tcherepanova I, Gamble AH, Horatinovich J, Harris J, Routy JP, et al. Immune function and viral load post AGS-004 administration to chronic HIV subjects undergoing STI. In: 2014 Conference on Retroviruses and Opportunistic Infections. Boston, MA; 2014.
• Background Marks P, Rifkind RA, Richon VM, Breslow R, Miller T, Kelly WK. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer. 2001 Dec;1(3):194-202. doi: 10.1038/35106079.
• Background Richon VM, Emiliani S, Verdin E, Webb Y, Breslow R, Rifkind RA, Marks PA. A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3003-7. doi: 10.1073/pnas.95.6.3003.
• Background Secrist JP, Zhou X, Richon VM. HDAC inhibitors for the treatment of cancer. Curr Opin Investig Drugs. 2003 Dec;4(12):1422-7.
• Background Munster PN, Troso-Sandoval T, Rosen N, Rifkind R, Marks PA, Richon VM. The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells. Cancer Res. 2001 Dec 1;61(23):8492-7.
• Background He LZ, Tolentino T, Grayson P, Zhong S, Warrell RP Jr, Rifkind RA, Marks PA, Richon VM, Pandolfi PP. Histone deacetylase inhibitors induce remission in transgenic models of therapy-resistant acute promyelocytic leukemia. J Clin Invest. 2001 Nov;108(9):1321-30. doi: 10.1172/JCI11537.
• Background Ruefli AA, Ausserlechner MJ, Bernhard D, Sutton VR, Tainton KM, Kofler R, Smyth MJ, Johnstone RW. The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10833-8. doi: 10.1073/pnas.191208598. Epub 2001 Sep 4.
• Background Huang L, Pardee AB. Suberoylanilide hydroxamic acid as a potential therapeutic agent for human breast cancer treatment. Mol Med. 2000 Oct;6(10):849-66.
• Background Butler LM, Agus DB, Scher HI, Higgins B, Rose A, Cordon-Cardo C, Thaler HT, Rifkind RA, Marks PA, Richon VM. Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. Cancer Res. 2000 Sep 15;60(18):5165-70.
• Background Vrana JA, Decker RH, Johnson CR, Wang Z, Jarvis WD, Richon VM, Ehinger M, Fisher PB, Grant S. Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53. Oncogene. 1999 Nov 25;18(50):7016-25. doi: 10.1038/sj.onc.1203176.
• Background Mitsiades N, Mitsiades CS, Richardson PG, McMullan C, Poulaki V, Fanourakis G, Schlossman R, Chauhan D, Munshi NC, Hideshima T, Richon VM, Marks PA, Anderson KC. Molecular sequelae of histone deacetylase inhibition in human malignant B cells. Blood. 2003 May 15;101(10):4055-62. doi: 10.1182/blood-2002-11-3514. Epub 2003 Jan 16.
• Background Lindemann RK, Gabrielli B, Johnstone RW. Histone-deacetylase inhibitors for the treatment of cancer. Cell Cycle. 2004 Jun;3(6):779-88. Epub 2004 Jun 14.
• Background Warrener R, Beamish H, Burgess A, Waterhouse NJ, Giles N, Fairlie D, Gabrielli B. Tumor cell-selective cytotoxicity by targeting cell cycle checkpoints. FASEB J. 2003 Aug;17(11):1550-2. doi: 10.1096/fj.02-1003fje. Epub 2003 Jun 3.
• Background Glaser KB, Staver MJ, Waring JF, Stender J, Ulrich RG, Davidsen SK. Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines. Mol Cancer Ther. 2003 Feb;2(2):151-63.
• Background Bali P, Pranpat M, Bradner J, Balasis M, Fiskus W, Guo F, Rocha K, Kumaraswamy S, Boyapalle S, Atadja P, Seto E, Bhalla K. Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem. 2005 Jul 22;280(29):26729-34. doi: 10.1074/jbc.C500186200. Epub 2005 Jun 2.
• Background 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 Jun;9(6):727-8. doi: 10.1038/nm880. Epub 2003 May 18.
• Background Archin NM, Crooks AM, Bateson R, Cope AB, Dahl NP, Eron J, et al. Measuring HIV Latency Over Time: Reservoir Stability and Assessing Interventions. In: Conference on Retroviruses and Opportunistic Infections. Boston, MA; 2014.
• Background Gandhi RT, Zheng L, Bosch RJ, Chan ES, Margolis DM, Read S, Kallungal B, Palmer S, Medvik K, Lederman MM, Alatrakchi N, Jacobson JM, Wiegand A, Kearney M, Coffin JM, Mellors JW, Eron JJ; AIDS Clinical Trials Group A5244 team. The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial. PLoS Med. 2010 Aug 10;7(8):e1000321. doi: 10.1371/journal.pmed.1000321.

Drugs

Indications