Enhancement by Poly-ICLC During HIV-1 Infection

NCT02071095 | Completed Phase 1 Results DMC

• 3 other identifiers: GCO 13-0482Campbell Foundation1R21AI110736-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study involves researching new approaches to treating HIV infection. Currently, HIV infection is treated with combinations of drugs called antiretrovirals. These drugs protect cells from infection by interfering with the viruses' ability to make copies of itself by infecting new target cells. Though these drugs are very effective, they cannot cure HIV infection and must be taken each and every day at prescribed doses to maintain their beneficial effect. This research study is investigating a new approach that involves an addition to existing medications. The study is investigating a medication called Poly-ICLC (Hiltonol®, Oncovir), which is an adjuvant. Adjuvants are medications that are designed to boost your body's immune responses resulting from a vaccine. The investigators want to test whether Poly-ICLC is an adjuvant that is effective in HIV-infected patients. A vaccine is not given in this study, but just investigating the adjuvant, Poly-ICLC, to determine whether it may be safe and useful in future vaccines that could be used to treat HIV, called therapeutic vaccines. One goal of future therapeutic vaccines is to reduce the virus that remains persistently inside of cells in a dormant or resting state despite treatment with HIV medications. This persistent pool is termed the "latent virus pool" or "viral reservoir". One tactic to reduce this viral reservoir is to first stimulate HIV to start replicating in order to force it out of hiding. Once viral replication occurs, the infected cells may then be recognized and killed by cells of the immune system. Therefore, we also want to see what effect Poly-ICLC has on the virus that lives inside of cells. Specifically, the investigators want to look at whether Poly-ICLC increases the level of virus inside your cells while also improving your immune system's responses. The investigators are doing this research in hope to find new ways to treat HIV infection that may reduce exposure to medications that are called antiretrovirals. Antiretrovirals are medications used to treat HIV infection. They are very effective but have side effects and have to be taken each and every day and cannot cure HIV.

Conditions

HIV-1 Infected Adults With Chronic HIV-1 Infection

Keywords

Human immunodeficiency virus 1; Combined Antiretroviral Therapy; Poly-ICLC; Adjuvant

Outcome Measures

Primary Outcomes (1)

• Number Participants With Adverse Events

  Safety measured by number of participants with adverse events.

  Up to 48 weeks

Secondary Outcomes (4)

• Plasma Interferon-gamma-inducible Protein-10 (IP-10) Level

  Day 2 and Day 4

• CD8 CD38 (Mean of Fluorescence)

  Day 8

• NK Cell Number

  at 48 weeks

• Percent Change in CD4+ Tcell-associated HIV-1 RNA as Compared to Baseline

  Baseline, Day 2, Day 4, Day 8, Day 28

Study Arms (2)

Arm A: Poly-ICLC

EXPERIMENTAL

Arm A (N=15): Patients will receive an injection of 1.4 mg of Poly-ICLC (Hiltonol®, Oncovir) subcutaneously on day 1 and day 2.

Drug: Arm A: Poly-ICLC

Arm B: Normal Saline

PLACEBO COMPARATOR

Arm B: (N=5): Patients will receive an injection of normal saline subcutaneously on day 1 and day 2.

Drug: Arm B: Normal Saline

Interventions

Arm A: Poly-ICLC DRUG

Poly-ICLC (Hiltonol®, Oncovir) Administration - On days 1 and 2, patients randomized to this arm will be injected subcutaneously in the arm with 1.4 mg of Poly-ICLC (Hiltonol®, Oncovir). Each subject will receive a total of 2 SC doses of Poly-ICLC. The volume of each injection is 0.7ml. The investigators who are blinded will not be present at the time of injection by the study nurse.

Also known as: Poly-ICLC (Hiltonol®, Oncovir)

Arm A: Poly-ICLC

Arm B: Normal Saline DRUG

Normal Saline - On days 1 and 2, patients randomized to this arm will be injected subcutaneously in the arm with normal saline obtained from the Rockefeller University Pharmacy. Each subject will receive a total of 2 SC doses of normal saline. The volume of each injection is 0.7ml. The investigators who are blinded will not be present at the time of injection by the study nurse.

Also known as: Placebo

Arm B: Normal Saline

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-1 infection documented by previous HIV-1 serology or rapid test, or documented plasma HIV-1 RNA of \>2000 copies/ml
• On stable cART regimen in accordance with the DHHS "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents" with documented virologic suppression (VL\<50 copies/ml) for ≥ 48 weeks.
• Baseline cell associated HIV-1 RNA is detectable (≥10copies/µg RNA)
• Laboratory values obtained within 30 days prior to study entry.
• VL \< 50 copies/ml
• CD4+ T cell count \> 500 cells/mm3
• Absolute neutrophil count (ANC) ≥500/mm3
• Hemoglobin ≥9.0 g/dL if female; 10 g/dL if male
• Platelet count ≥75,000/mm3
• AST (SGOT), ALT (SGPT) ≤3.5 × ULN
• Alkaline phosphatase\< 2.5 ULN
• Total bilirubin ≤2.5 x ULN
• Lipase ≤2.5 x ULN
• Calculated creatinine clearance ≥70 mL/min as estimated by the Cockcroft-Gault equation:
• For men(140-age in yrs)x(body wt in kg)÷(serum creatinine in mg/dLx72)=CrCl (mL/min)\*

You may not qualify if:

• Previous immune based therapy
• History of vascular disease including h/o coronary artery disease, angina/MI, TIA/CVA, peripheral vascular disease/claudication
• Strong family history of cardiovascular disease
• Hyperlipidemia requiring medication
• Diabetes
• History of Tobacco use (≥10 pack years)
• HIV-related nephropathy
• History of vascular disease including history of coronary artery disease, angina/MI, TIA/CVA, peripheral vascular disease/claudication, poorly controlled hypertension
• Pregnancy or currently breast-feeding
• Desire to become pregnant during the course of study
• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
• Known allergy/sensitivity to study drugs or their formulations.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• History of autoimmunity
• Chronic Hepatitis B (HepBSAg+) or C (HCV RNA positive)

Sponsors & Collaborators

• Nina Bhardwaj: lead
• The Campbell Foundation: collaborator
• Oncovir, Inc.: collaborator
• National Institutes of Health (NIH): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

The Rockefeller University Hospital

New York, New York, 10065, United States

Location

Related Publications (50)

• 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.

  PMID: 22837004 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.

  PMID: 22406268 BACKGROUND

• Xing S, Bullen CK, Shroff NS, Shan L, Yang HC, Manucci JL, Bhat S, Zhang H, Margolick JB, Quinn TC, Margolis DM, Siliciano JD, Siliciano RF. Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation. J Virol. 2011 Jun;85(12):6060-4. doi: 10.1128/JVI.02033-10. Epub 2011 Apr 6.

  PMID: 21471244 BACKGROUND

• Xing S, Siliciano RF. Targeting HIV latency: pharmacologic strategies toward eradication. Drug Discov Today. 2013 Jun;18(11-12):541-51. doi: 10.1016/j.drudis.2012.12.008. Epub 2012 Dec 25.

  PMID: 23270785 BACKGROUND

• Elliot, J., et al. The Safety and Effect of Multiple Doses of Vorinostat on HIV Transcription in HIV+ Patients Receiving cART. in Conference on Retroviruses and Opportunistic Infections (CROI) (2013).

  BACKGROUND

• Almeida M, Cordero M, Almeida J, Orfao A. Different subsets of peripheral blood dendritic cells show distinct phenotypic and functional abnormalities in HIV-1 infection. AIDS. 2005 Feb 18;19(3):261-71.

  PMID: 15718836 BACKGROUND

• Almeida M, Cordero M, Almeida J, Orfao A. Persistent abnormalities in peripheral blood dendritic cells and monocytes from HIV-1-positive patients after 1 year of antiretroviral therapy. J Acquir Immune Defic Syndr. 2006 Apr 1;41(4):405-15. doi: 10.1097/01.qai.0000209896.82255.d3.

  PMID: 16652047 BACKGROUND

• Almeida M, Cordero M, Almeida J, Orfao A. Abnormal cytokine production by circulating monocytes and dendritic cells of myeloid origin in ART-treated HIV-1+ patients relates to CD4+ T-cell recovery and HCV co-infection. Curr HIV Res. 2007 May;5(3):325-36. doi: 10.2174/157016207780636524.

  PMID: 17504174 BACKGROUND

• Anthony DD, Yonkers NL, Post AB, Asaad R, Heinzel FP, Lederman MM, Lehmann PV, Valdez H. Selective impairments in dendritic cell-associated function distinguish hepatitis C virus and HIV infection. J Immunol. 2004 Apr 15;172(8):4907-16. doi: 10.4049/jimmunol.172.8.4907.

  PMID: 15067070 BACKGROUND

• Buisson S, Benlahrech A, Gazzard B, Gotch F, Kelleher P, Patterson S. Monocyte-derived dendritic cells from HIV type 1-infected individuals show reduced ability to stimulate T cells and have altered production of interleukin (IL)-12 and IL-10. J Infect Dis. 2009 Jun 15;199(12):1862-71. doi: 10.1086/599122.

  PMID: 19419334 BACKGROUND

• Chang JJ, Lacas A, Lindsay RJ, Doyle EH, Axten KL, Pereyra F, Rosenberg ES, Walker BD, Allen TM, Altfeld M. Differential regulation of toll-like receptor pathways in acute and chronic HIV-1 infection. AIDS. 2012 Mar 13;26(5):533-41. doi: 10.1097/QAD.0b013e32834f3167.

  PMID: 22210629 BACKGROUND

• Fan Z, Huang XL, Kalinski P, Young S, Rinaldo CR Jr. Dendritic cell function during chronic hepatitis C virus and human immunodeficiency virus type 1 infection. Clin Vaccine Immunol. 2007 Sep;14(9):1127-37. doi: 10.1128/CVI.00141-07. Epub 2007 Jul 18.

  PMID: 17634507 BACKGROUND

• Granelli-Piperno A, Golebiowska A, Trumpfheller C, Siegal FP, Steinman RM. HIV-1-infected monocyte-derived dendritic cells do not undergo maturation but can elicit IL-10 production and T cell regulation. Proc Natl Acad Sci U S A. 2004 May 18;101(20):7669-74. doi: 10.1073/pnas.0402431101. Epub 2004 May 5.

  PMID: 15128934 BACKGROUND

• Hodges A, Sharrocks K, Edelmann M, Baban D, Moris A, Schwartz O, Drakesmith H, Davies K, Kessler B, McMichael A, Simmons A. Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication. Nat Immunol. 2007 Jun;8(6):569-77. doi: 10.1038/ni1470. Epub 2007 May 13.

  PMID: 17496896 BACKGROUND

• Lester RT, Yao XD, Ball TB, McKinnon LR, Kaul R, Wachihi C, Jaoko W, Plummer FA, Rosenthal KL. Toll-like receptor expression and responsiveness are increased in viraemic HIV-1 infection. AIDS. 2008 Mar 30;22(6):685-94. doi: 10.1097/QAD.0b013e3282f4de35.

  PMID: 18356597 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.

  PMID: 15956545 BACKGROUND

• Sabado RL, O'Brien M, Subedi A, Qin L, Hu N, Taylor E, Dibben O, Stacey A, Fellay J, Shianna KV, Siegal F, Shodell M, Shah K, Larsson M, Lifson J, Nadas A, Marmor M, Hutt R, Margolis D, Garmon D, Markowitz M, Valentine F, Borrow P, Bhardwaj N. Evidence of dysregulation of dendritic cells in primary HIV infection. Blood. 2010 Nov 11;116(19):3839-52. doi: 10.1182/blood-2010-03-273763. Epub 2010 Aug 6.

  PMID: 20693428 BACKGROUND

• Shan M, Klasse PJ, Banerjee K, Dey AK, Iyer SP, Dionisio R, Charles D, Campbell-Gardener L, Olson WC, Sanders RW, Moore JP. HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells. PLoS Pathog. 2007 Nov;3(11):e169. doi: 10.1371/journal.ppat.0030169.

  PMID: 17983270 BACKGROUND

• Smed-Sorensen A, Lore K, Walther-Jallow L, Andersson J, Spetz AL. HIV-1-infected dendritic cells up-regulate cell surface markers but fail to produce IL-12 p70 in response to CD40 ligand stimulation. Blood. 2004 Nov 1;104(9):2810-7. doi: 10.1182/blood-2003-07-2314. Epub 2004 Jul 1.

  PMID: 15231570 BACKGROUND

• Tan DB, Yong YK, Lim A, Tan HY, Kamarulzaman A, French M, Price P. Robust interferon-alpha and IL-12 responses by dendritic cells are related to efficient CD4+ T-cell recovery in HIV patients on ART. Clin Immunol. 2011 May;139(2):115-21. doi: 10.1016/j.clim.2011.02.015. Epub 2011 Feb 23.

  PMID: 21429806 BACKGROUND

• Yonkers NL, Rodriguez B, Asaad R, Lederman MM, Anthony DD. Systemic immune activation in HIV infection is associated with decreased MDC responsiveness to TLR ligand and inability to activate naive CD4 T-cells. PLoS One. 2011;6(9):e23884. doi: 10.1371/journal.pone.0023884. Epub 2011 Sep 1.

  PMID: 21912648 BACKGROUND

• Frleta D, Ochoa CE, Kramer HB, Khan SA, Stacey AR, Borrow P, Kessler BM, Haynes BF, Bhardwaj N. HIV-1 infection-induced apoptotic microparticles inhibit human DCs via CD44. J Clin Invest. 2012 Dec;122(12):4685-97. doi: 10.1172/JCI64439. Epub 2012 Nov 19.

  PMID: 23160198 BACKGROUND

• Dillon SM, Robertson KB, Pan SC, Mawhinney S, Meditz AL, Folkvord JM, Connick E, McCarter MD, Wilson CC. Plasmacytoid and myeloid dendritic cells with a partial activation phenotype accumulate in lymphoid tissue during asymptomatic chronic HIV-1 infection. J Acquir Immune Defic Syndr. 2008 May 1;48(1):1-12. doi: 10.1097/QAI.0b013e3181664b60.

  PMID: 18300699 BACKGROUND

• Butera ST, Roberts BD, Folks TM. Regulation of HIV-1 expression by cytokine networks in a CD4+ model of chronic infection. J Immunol. 1993 Jan 15;150(2):625-34.

  PMID: 8380428 BACKGROUND

• Hoshino S, Konishi M, Mori M, Shimura M, Nishitani C, Kuroki Y, Koyanagi Y, Kano S, Itabe H, Ishizaka Y. HIV-1 Vpr induces TLR4/MyD88-mediated IL-6 production and reactivates viral production from latency. J Leukoc Biol. 2010 Jun;87(6):1133-43. doi: 10.1189/jlb.0809547. Epub 2010 Feb 9.

  PMID: 20145198 BACKGROUND

• McNamara LA, Ganesh JA, Collins KL. Latent HIV-1 infection occurs in multiple subsets of hematopoietic progenitor cells and is reversed by NF-kappaB activation. J Virol. 2012 Sep;86(17):9337-50. doi: 10.1128/JVI.00895-12. Epub 2012 Jun 20.

  PMID: 22718820 BACKGROUND

• Nabel G, Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16-22;326(6114):711-3. doi: 10.1038/326711a0.

  PMID: 3031512 BACKGROUND

• Poli G, Kinter A, Justement JS, Kehrl JH, Bressler P, Stanley S, Fauci AS. Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. Proc Natl Acad Sci U S A. 1990 Jan;87(2):782-5. doi: 10.1073/pnas.87.2.782.

  PMID: 2300561 BACKGROUND

• Saleh S, Wightman F, Ramanayake S, Alexander M, Kumar N, Khoury G, Pereira C, Purcell D, Cameron PU, Lewin SR. Expression and reactivation of HIV in a chemokine induced model of HIV latency in primary resting CD4+ T cells. Retrovirology. 2011 Oct 12;8:80. doi: 10.1186/1742-4690-8-80.

  PMID: 21992606 BACKGROUND

• Tiemessen CT, Kilroe B, Martin DJ. Interleukin-8 fails to induce human immunodeficiency virus-1 expression in chronically infected promonocytic U1 cells but differentially modulates induction by proinflammatory cytokines. Immunology. 2000 Sep;101(1):140-6. doi: 10.1046/j.1365-2567.2000.00100.x.

  PMID: 11012765 BACKGROUND

• Winckelmann, A., et al. Toll-like Receptor 9 Agonist Treatment Decreases the Proviral Reservoir in Peripheral Blood and Could Impact HIV-specific Immunity in Patients on cART. Conference on Retroviruses and Opportunistic Infections (CROI) (2013).

  BACKGROUND

• Saleh S, Solomon A, Wightman F, Xhilaga M, Cameron PU, Lewin SR. CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T cells to HIV-1 infection: a novel model of HIV-1 latency. Blood. 2007 Dec 15;110(13):4161-4. doi: 10.1182/blood-2007-06-097907. Epub 2007 Sep 19.

  PMID: 17881634 BACKGROUND

• Schulz O, Diebold SS, Chen M, Naslund TI, Nolte MA, Alexopoulou L, Azuma YT, Flavell RA, Liljestrom P, Reis e Sousa C. Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature. 2005 Feb 24;433(7028):887-92. doi: 10.1038/nature03326. Epub 2005 Feb 13.

  PMID: 15711573 BACKGROUND

• Wille-Reece U, Flynn BJ, Lore K, Koup RA, Miles AP, Saul A, Kedl RM, Mattapallil JJ, Weiss WR, Roederer M, Seder RA. Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates. J Exp Med. 2006 May 15;203(5):1249-58. doi: 10.1084/jem.20052433. Epub 2006 Apr 24.

  PMID: 16636134 BACKGROUND

• Zhang Z, Kim T, Bao M, Facchinetti V, Jung SY, Ghaffari AA, Qin J, Cheng G, Liu YJ. DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Immunity. 2011 Jun 24;34(6):866-78. doi: 10.1016/j.immuni.2011.03.027.

  PMID: 21703541 BACKGROUND

• Zhang Z, Yuan B, Lu N, Facchinetti V, Liu YJ. DHX9 pairs with IPS-1 to sense double-stranded RNA in myeloid dendritic cells. J Immunol. 2011 Nov 1;187(9):4501-8. doi: 10.4049/jimmunol.1101307. Epub 2011 Sep 28.

  PMID: 21957149 BACKGROUND

• Akazawa T, Ebihara T, Okuno M, Okuda Y, Shingai M, Tsujimura K, Takahashi T, Ikawa M, Okabe M, Inoue N, Okamoto-Tanaka M, Ishizaki H, Miyoshi J, Matsumoto M, Seya T. Antitumor NK activation induced by the Toll-like receptor 3-TICAM-1 (TRIF) pathway in myeloid dendritic cells. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):252-7. doi: 10.1073/pnas.0605978104. Epub 2006 Dec 26.

  PMID: 17190817 BACKGROUND

• Bogunovic D, Manches O, Godefroy E, Yewdall A, Gallois A, Salazar AM, Marie I, Levy DE, Bhardwaj N. TLR4 engagement during TLR3-induced proinflammatory signaling in dendritic cells promotes IL-10-mediated suppression of antitumor immunity. Cancer Res. 2011 Aug 15;71(16):5467-76. doi: 10.1158/0008-5472.CAN-10-3988. Epub 2011 Jul 5.

  PMID: 21730023 BACKGROUND

• Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, Kluger C, Salazar AM, Colonna M, Steinman RM. Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med. 2009 Jul 6;206(7):1589-602. doi: 10.1084/jem.20090247. Epub 2009 Jun 29.

  PMID: 19564349 BACKGROUND

• Stahl-Hennig C, Eisenblatter M, Jasny E, Rzehak T, Tenner-Racz K, Trumpfheller C, Salazar AM, Uberla K, Nieto K, Kleinschmidt J, Schulte R, Gissmann L, Muller M, Sacher A, Racz P, Steinman RM, Uguccioni M, Ignatius R. Synthetic double-stranded RNAs are adjuvants for the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesus macaques. PLoS Pathog. 2009 Apr;5(4):e1000373. doi: 10.1371/journal.ppat.1000373. Epub 2009 Apr 10.

  PMID: 19360120 BACKGROUND

• Tewari K, Flynn BJ, Boscardin SB, Kastenmueller K, Salazar AM, Anderson CA, Soundarapandian V, Ahumada A, Keler T, Hoffman SL, Nussenzweig MC, Steinman RM, Seder RA. Poly(I:C) is an effective adjuvant for antibody and multi-functional CD4+ T cell responses to Plasmodium falciparum circumsporozoite protein (CSP) and alphaDEC-CSP in non human primates. Vaccine. 2010 Oct 21;28(45):7256-66. doi: 10.1016/j.vaccine.2010.08.098. Epub 2010 Sep 21.

  PMID: 20846528 BACKGROUND

• Vagenas P, Aravantinou M, Williams VG, Jasny E, Piatak M Jr, Lifson JD, Salazar AM, Blanchard JL, Gettie A, Robbiani M. A tonsillar PolyICLC/AT-2 SIV therapeutic vaccine maintains low viremia following antiretroviral therapy cessation. PLoS One. 2010 Sep 21;5(9):e12891. doi: 10.1371/journal.pone.0012891.

  PMID: 20877632 BACKGROUND

• Zobywalski A, Javorovic M, Frankenberger B, Pohla H, Kremmer E, Bigalke I, Schendel DJ. Generation of clinical grade dendritic cells with capacity to produce biologically active IL-12p70. J Transl Med. 2007 Apr 12;5:18. doi: 10.1186/1479-5876-5-18.

  PMID: 17430585 BACKGROUND

• Checkley Luttge, M., et al. Natural Killer Cells Can Target and Eliminate Latently HIV-1-Infected Primary T cells following Proviral Reactivation. Conference on Retroviruses and Opportunistic Infections (CROI) (2013).

  BACKGROUND

• Caskey M, Lefebvre F, Filali-Mouhim A, Cameron MJ, Goulet JP, Haddad EK, Breton G, Trumpfheller C, Pollak S, Shimeliovich I, Duque-Alarcon A, Pan L, Nelkenbaum A, Salazar AM, Schlesinger SJ, Steinman RM, Sekaly RP. Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans. J Exp Med. 2011 Nov 21;208(12):2357-66. doi: 10.1084/jem.20111171. Epub 2011 Nov 7.

  PMID: 22065672 BACKGROUND

• Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, Mintz AH, Engh JA, Bartlett DL, Brown CK, Zeh H, Holtzman MP, Reinhart TA, Whiteside TL, Butterfield LH, Hamilton RL, Potter DM, Pollack IF, Salazar AM, Lieberman FS. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with alpha-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol. 2011 Jan 20;29(3):330-6. doi: 10.1200/JCO.2010.30.7744. Epub 2010 Dec 13.

  PMID: 21149657 BACKGROUND

• Poly-ICLC Investigational Brochure (Hiltonol®, Oncovir).

  BACKGROUND

• Trumpfheller C, Longhi MP, Caskey M, Idoyaga J, Bozzacco L, Keler T, Schlesinger SJ, Steinman RM. Dendritic cell-targeted protein vaccines: a novel approach to induce T-cell immunity. J Intern Med. 2012 Feb;271(2):183-92. doi: 10.1111/j.1365-2796.2011.02496.x. Epub 2012 Jan 4.

  PMID: 22126373 BACKGROUND

• Marcus PI, Sekellick MJ. Combined sequential treatment with interferon and dsRNA abrogates virus resistance to interferon action. J Interferon Cytokine Res. 2001 Jun;21(6):423-9. doi: 10.1089/107999001750277907.

  PMID: 11440640 BACKGROUND

• Saxena M, Sabado RL, La Mar M, Mohri H, Salazar AM, Dong H, Correa Da Rosa J, Markowitz M, Bhardwaj N, Miller E. Poly-ICLC, a TLR3 Agonist, Induces Transient Innate Immune Responses in Patients With Treated HIV-Infection: A Randomized Double-Blinded Placebo Controlled Trial. Front Immunol. 2019 Apr 9;10:725. doi: 10.3389/fimmu.2019.00725. eCollection 2019.

  PMID: 31024557 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

poly ICLC

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

Small sample size, gender homogeneity, and exclusion of older individuals (\>55 years) and common comorbidities such as cardiovascular disease and diabetes limit the generalizability of the safety findings in the HIV-infected population as a whole.

Results Point of Contact

• Title: Dr. Nina Bhardwaj
• Organization: Icahn School of Medicine at Mount Sinai

nina.bhardwaj@mssm.edu

212-824-8427

Study Officials

• Nina Bhardwaj, MD, PhD

  Icahn School of Medicine at Mt. Sinai

  STUDY DIRECTOR

• Elizabeth Miller, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Martin Markowitz, MD

  Aaron Diamond AIDS Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Medicine - Director, Immunotherapy Program

Study Record Dates

• First Submitted: February 21, 2014
• First Posted: February 25, 2014
• Study Start: April 1, 2014
• Primary Completion: July 26, 2016
• Study Completion: July 26, 2016
• Last Updated: March 13, 2018
• Results First Posted: March 13, 2018

Record last verified: 2018-02

Locations

US (1)