HIV Apheresis Tags (HIVAT) Aided Elimination of Viremia

  • Marek Malecki Phoenix Biomolecular Engineering Foundation (PBMEF), San Francisco, CA, USA
  • Bianka Saetre Phoenix Biomolecular Engineering Foundation (PBMEF)
Keywords: Human Immunodeficiency Virus (HIV), viremia, Acquired Immunodeficiency Syndrome (AIDS)


Abstract: HIV viremia is the essential element for progression of an initial HIV infection into AIDS and death. The currently approved management relies primarily on chemotherapy repressing the HIV replication in the infected CD4+ cells, although with severe systemic adverse effects. The problem is that it does not physically eliminate viruses, which then not only keep infecting healthy cells of these patients, but also promote infectivions of other people.



Download data is not yet available.



WHO. AIDS. Fact sheet - Latest statistics on the status of the AIDS epidemic. resources/fact-sheet

NIH. HIV-AIDS-Statistics. news/168/hiv-aids-statistics- downloaded 06DEC2017

Fauci AS; Lane HC. 226: Human Immunodeficiency Virus Disease: AIDS and Related Disorders. https:// In: Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo eds. Harrison’s Internal Medicine. 19th edition. https:// accessmedicine. mhmedical. com/ book. aspx?bookID=1130 downloaded 06DEC2017

NIH. AIDS. Fact sheet – Preventive vaccine. sheets/19/96/what-is-a-preventive-hiv-vaccine- downloaded 06DEC2017

Rios A. Fundamental challenges to the development of a preventive HIV vaccine. Current Opinion in Virology. 2018; 29:26-32.

Trovato M, D'Apice L, Prisco A, De Berardinis P. HIV Vaccination: A Roadmap among Advancements and Concerns. Int J Mol Sci. 2018; 19(4). pii: E1241.

Gao Y, McKay PF, Mann JFS. Advances in HIV-1 Vaccine Development. Viruses. 2018; 10(4): 1-16.

Malecki M, Saetre BK. HIV Universal Vaccines. Molecular and Cellular Therapies. 2018; 6: 1-21.

Feorino PM, Jaffe HW, Palmer E, Peterman TA, Francis DP, Kalyanaraman VS, Weinstein RA, Stoneburner RL, Alexander WJ, Raevsky C, Getchell JP, Warfield D. Transfusion-associated acquired immunodeficiency syndrome. Evidence for persistent infection in blood donors. N Engl J Med. 1985; 312(20):1293-1296.

Coombs RW1, Collier AC, Allain JP, Nikora B, Leuther M, Gjerset GF, Corey L. Plasma viremia in human immunodeficiency virus infection. N Engl J Med. 1989; 321(24):1626-1631.

Pan LZ, Werner A, Levy JA. Detection of plasma viremia in human immunodeficiency virus-infected individuals at all clinical stages. J Clin Microbiol. 1993; 31(2):283-8.

Saag MS, Crain MJ, Decker WD, Campbell-Hill S, Robinson S, Brown WE, Leuther M, Whitley RJ, Hahn BH, Shaw GM. High-level viremia in adults and children infected with human immunodeficiency virus: relation to disease stage and CD4+ lymphocyte levels. J Infect Dis. 1991; 164(1):72-80.

Clark SJ, Saag MS, Decker WD, Campbell-Hill S, Roberson JL, Veldkamp PJ, Kappes JC, Hahn BH, Shaw GM. High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N Engl J Med. 1991; 324(14):954-60.

Daar ES, Moudgil T, Meyer RD, Ho DD. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N Engl J Med. 1991; 324(14):961-4.

Graziosi C, Pantaleo G, Butini L, Demarest JF, Saag MS, Shaw GM, Fauci AS. Kinetics of human immunodeficiency virus type 1 (HIV-1) DNA and RNA synthesis during primary HIV-1 infection. Proc Natl Acad Sci U S A. 1993; 90(14):6405-9.

Menzo S, Bagnarelli P, Giacca M, Manzin A, Varaldo PE, Clementi M. Absolute quantitation of viremia in human immunodeficiency virus infection by competitive reverse transcription and polymerase chain reaction. J Clin Microbiol. 1992; 30(7):1752-1757.

Ho DD, Moudgil T, Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med 1989; 321:1621–1625.

Schnittman SM, Psallidopoulous MC, Lane HC. The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science 1989; 245:305–8.

Cummins NW, Badley AD. Mechanisms of HIV- associated lymphocyte apoptosis: 2010. Cell Death Dis. 2010 Nov 11;1:e99.

Dagleish AG, Beverly PCL, Clapham PR, Crawford DH, Greaves MF, Weiss RA. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1983; 312: 763-765.

Sodroski J, Goh WC, Rosen C, Campbell K, Haseltine W. Role of HTLV-III/LAV envelope in syncytium formation and cytopathicity . Nature 1986; 322:470– 474.

El-Farrash MA, Harada S. Syncytium-Inducing Capacity of Human Immunodeficiency Virus (HIV): Analysis by the Use of Cloned Viruses. Microbiol. Immunol. 1989; 33: 549-559.

Zhang LQ, MacKenzie P, Cleland A, Holmes EC, Brown AJ, Simmonds P. Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection.

J Virol. 1993; 67(6):3345-56.

Yourno J, Conroy J. A novel polymerase chain reaction method for detection of human immunodeficiency virus in dried blood spots on filter paper. J Clin Microbiol. 1992; 30(11):2887-92.

van Bueren J, Simpson RA, Jacobs P, Cookson BD. Survival of human immunodeficiency virus in suspension and dried onto surfaces. J Clin Microbiol. 1994; 32(2):571-4.

Yourno J. Direct polymerase chain reaction for detection of human immunodeficiency virus in blood spot residues on filter paper after elution of antibodies: an adjunct to serological surveys for estimating vertical transmission rates among human immunodeficiency virus antibody-positive newborns. J Clin Microbiol. 1993; 31(5):1364-1367.

Mulder J, McKinney N, Christopherson C, Sninsky J, Greenfield L, Kwok S. Rapid and simple PCR assay for quantitation of human immunodeficiency virus type 1 RNA in plasma: application to acute retroviral infection. J Clin Microbiol. 1994; 32(2):292-300.

Gaines H, Albert J, von Sydow M, Sönnerborg A, Chiodi F, Ehrnst A, Strannegård O, Asjö B. HIV antigenaemia and virus isolation from plasma during primary HIV infection. Lancet. 1987; 1(8545):1317-8.

Chess Q, Daniels J, North E, Macris NT. Serum i m m u n o g l o b u l i n e l e v a t i o n s i n t h e a c q u i r e d immunodeficiency syndrome (AIDS): IgG, IgA, IgM, and IgD. Diagn Immunol. 1984; 2(3):148-53.

Goudsmit J, Miedema F, Wijngaarden-du Bois RJ, Roos MT, Schellekens PT, Coutinho RA, van der Noordaa J, Melief CJ. Immunoglobulin subclasses of antibodies to human T-cell leukemia/lymphoma virus I-associated antigens in acquired immune deficiency syndrome and lymphadenopathy syndrome. J Virol. 1985; 53(1):287-291.

Aiuti F, Rossi P, Sirianni MC, Carbonari M, Popovic M, Sarngadharan MG, Contu L, Moroni M, Romagnani S, Gallo RC. IgM and IgG antibodies to human T cell lymphotropic retrovirus (HTLV-III) in lymphadenopathy syndrome and subjects at risk for AIDS in Italy. Br Med J (Clin Res Ed). 1985; 291(6489):165-6

Gaines H, von Sydow M, Sönnerborg A, Albert J, Czajkowski J, Pehrson PO, Chiodi F, Moberg L, Fenyö EM, Asjö B, Forsgren M. Antibody response in primary human immunodeficiency virus infection. Lancet. 1987; 1(8544):1249-53.

Kenealy W, Reed D, Cybulski R, Tribe D, Taylor P, Stevens C, Matthews T, Petteway S. Analysis of human serum antibodies to human immunodeficiency virus (HIV) using recombinant Env and Gag antigens. AIDS Res Hum Retroviruses. 1987; 3(1):95-105.

Sarngadharan MG, Popovic M, Bruch L, Schüpbach J, Gallo RC. Antibodies reactive with human T-lymphotropic (HTLV-Ill) in the serum of patients with AIDS. Science. 1984; 224:506-508.

Geroldi D, Aricò M, Plebani A, Maccario R, Notarangelo LD, Duse M, Rey F, Barrè Sinoussi F, Chermann JC, Burgio GR. Western blot technique

in the serological evaluation of three LAV/HTLV III- infected Italian families. Infection. 1986; 14(2):60-3.

NIH. AIDS. Fact sheet – Therapeutic vaccine. sheets/19/91/what-is-a-therapeutic-hiv-vaccine- downloaded 06DEC2017

Traunecker A1, Lüke W, Karjalainen K. Soluble CD4 molecules neutralize human immunodeficiency virus type 1. Nature. 1988; 331(6151): 84-6.

Fisher RA, Bertonis JM, Meier W, Johnson VA, Costopoulos DS, Liu T, Tizard R, Walker BD, Hirsch MS, Schooley RT, Flavell RA. HIV infection is blocked in vitro by recombinant soluble CD4. Nature. 1988; 331(6151): 76-78.

Bruel T, Guivel-Benhassine F, Amraoui S, Malbec M, Richard L, Bourdic K, Donahue DA, Lorin V, Casartelli N, Noël N, Lambotte O, Mouquet H, Schwartz O. Elimination of HIV-infected cells by broadly neutralizing antibodies. Nature Communications. 2016; 3; 7:10844.

Hua CK, Ackerman ME. Increasing the clinical potential and applications of anti-HIV antibodies. Front Immunol. 2017; 8:1655.

Hodges TL, Kahn JO, Kaplan LD, Groopman JE, Volberding PA, Amman AJ, Arri CJ, Bouvier LM, Mordenti J, Izu AE. 1991. Phase 1 study of recombinant CD 4 - Immunoglobulin G therapy of patients with AIDS. Antimrobial Agents and Chemotherapy. 1991; 35 (12): 2580-2586.

Arthos J, Cicala C, Steenbeke TD, Chun TW, Dela Cruz C, Hanback DB, Khazanie P, Nam D, Schuck P, Selig SM, Van Ryk D, Chaikin MA, Fauci AS. Biochemical characterization of dodecameric CD4- Ig fusion protein. J. Biol. Chem. 2002; 277(130): 11456-11464.

Bosch B, Blanco J, Pauls E, Clotet-Codina I, Armand- Ugón M, Grigorov B, Muriaux D, Clotet B, Darlix JL, Esté JA. Inhibition of coreceptor-independent cell-to-cell human immunodeficiency virus type 1 transmission by a CD4-immunoglobulin G2 fusion protein. Antimicrob Agents Chemother. 2005 ; 49(10):4296-304.

Yu S, Yao Y, Xiao H, Li J, Liu Q, Yang Y, Adah D, Lu J, Zhao S, Qin L, Chen X. Simultaneous Knockout of CXCR4 and CCR5 Genes in CD4+ T Cells via CRISPR/Cas9 Confers Resistance to Both X4- and R5-Tropic Human Immunodeficiency Virus Type 1 Infection. Hum Gene Ther. 2018; 29(1):51-67.

Liu Z, Chen S, Jin X, Wang Q, Yang K, Li C, Xiao Q, Hou P, Liu S, Wu S, Hou W, Xiong Y, Kong C, Zhao X, Wu L, Li C, Sun G, Guo D. Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4+ T cells from HIV-1 infection. Cell Biosci. 2017;7:47

Hou P, Chen S, Wang S, Yu X, Chen Y, Jiang M, Zhuang K, Ho W, Hou W, Huang J, Guo D. Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection. Sci Rep. 2015; 5:15577.

Li C, Guan X, Du T, Jin W, Wu B, Liu Y, Wang P, Hu B, Griffin GE, Shattock RJ, Hu Q. Inhibition of HIV-1

infection of primary CD4+ T-cells by gene editing of CCR5 using adenovirus-delivered CRISPR/Cas9. J Gen Virol. 2015; 96(8):2381-93.

Nerys-Junior A, Braga-Dias LP, Pezzuto P, Cotta-de- Almeida V, Tanuri A.Comparison of the editing patterns and editing efficiencies of TALEN and CRISPR-Cas9 when targeting the human CCR5 gene. Genet Mol Biol. 2018; 41(1):167-179.

NIH. AIDS. Fact sheet - Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV downloaded 06DEC2017

NIH. AIDS. Fact sheet - HIV medicines and side effects. aids/fact-sheets/22/63/hiv-medicines-and-side-effects downloaded 06DEC2017

NIH. AIDS. Guidelines. Laboratory Testing for Initial Assessment and Monitoring of Patients with HIV Receiving Antiretroviral Therapy. https://aidsinfo.nih. gov/guidelines/html/1/adult-and-adolescent-arv/3/ tests-for-initial-assessment-and-follow-up downloaded 06DEC2017

Cummins NW, Sainski AM, Natesampillai S, Bren GD, Badley AD. Choice of antiretroviral therapy differentially impacts survival of HIV-infected CD4 T cells. Mol Cell Ther. 2014; 2:1.

Papaevangelou G, Economidou J, Kallinikos J, Choreimi H, Mandalaki T, Stratigos J, Geroldi D, Barre-Sinoussi F, Chermann JC, Montagnier L. Lymphadenopathy associated virus in AIDS, lymphadenopathy associated syndrome, and classic Kaposi patients in Greece. Lancet. 1984; 2(8403):642.

O'Brien RF1, Cohn DL. Serosanguineous pleural effusions in AIDS-associated Kaposi's sarcoma. Chest. 1989; 96(3):460-466.

Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983; 220(4599):868-871.

Gallo RC, Sarin PS, Gelmann EP, Robert-Guroff M, Richardson E, Kalyanaraman VS, Mann D, Sidhu GD, Stahl RE, Zolla-Pazner S, Leibowitch J, Popovic M. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science. 1983; 220(4599):865-867.

Popovic M, Sarngadharan MG, Read E, Gallo RC. Detection, isolation, and continuous production o f c y t o p a t h i c r e t r o v i r u s e s ( H T LV- I I I ) f r o m patients with AIDS and pre-AIDS. Science. 1984; 224(4648):497-500.

Ehrnst A1, Sönnerborg A, Bergdahl S, Strannegård

O. Efficient isolation of HIV from plasma during different stages of HIV infection. J Med Virol. 1988; 26(1):23-32.

HIV Culture Manual. Berkeley, CA, California State Health Department, 1986.

Gallo D, Kimpton JS, Dailey PJ. Comparative studies

on use of fresh and frozen peripheral blood lymphocyte specimens for isolation of human immunodeficiency virus and effects of cell lysis on isolation efficiency. J Clin Microbiol. 1987; 25(7):1291-4.

Gallo D, Kimpton JS, Johnson PJ. Isolation of human immunodeficiency virus from peripheral blood lymphocytes stored in various transport media and frozen at -60 degrees C. J Clin Microbiol. 1989; 27(1):88-90.

Malecki M, Hsu A, Truong L, Sanchez S. Molecular immunolabeling with recombinant single-chain variable fragment (scFv) antibodies designed with metal binding domains. Proc. Natl. Acad. Sci. U. S. A. 2001; 99: 213-219.

Malecki M, Szybalski W. Isolation of single, intact chromosomes from single, selected ovarian cancer cells for in situ hybridization and next generation sequencing. Gene. 2012; 493(1): 132-139.

Szybalska EH, Szybalski W. Genetics of human cell line. IV. DNA-mediated heritable transformation of a biochemical trait. Proc. Natl. Acad. Sci. U.S.A. 1962; 48: 2026-2034.

Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate- phenol-chloroform extraction. Anal. Biochem. 1987; 162:156-159.

Alizon M, Sonigo P, Barré-Sinoussi F, Chermann JC, Tiollais P, Montagnier L, Wain-Hobson S. Molecular cloning of lymphadenopathy-associated virus. Nature. 1984; 312(5996):757-60.

Wain-Hobson S, Sonigo P, Danos O, Cole S, Alizon

M. Nucleotide sequence of the AIDS virus, LAV. Cell. 1985; 40(1):9-17.

Wong-Staal F, Gallo RC, Chang NT, Ghrayeb J, Papas TS, Lautenber VER JA, Pearson ML, Petteway SR Jr., Ivanoff L., Baumeister K., Whitehorn EA, Rafalski JA, Doran ER., Josephs SJ, Starcich B, Livak KJ, Patarca R, Haseltine WA, Ratner L. Complete nucleotide sequence of the AIDS virus, HTLV-III Nature. 1985; 313 (6000): 277-284.

Maddon JP, Molineaux SE, Maddon DE, Zimmerman KA, Godfrey M, Alt FW, Chess L, Axel R. Structure and expression of the human and mouse T4 genes. Proc. Natl. Acad. Sci. U.S.A. 1987; 84:9155-9159.

Malecki M, Putzer E, Caroline Quach C, DodivenakaC, Tombokan X. Novel paradigm for immunotherapy of breast cancer by engaging prophylactic immunity against hepatitis B. Clin. Trans. Med. 2016; 5(32):1-12.

Malecki M, Sabo C, Foorohar A, Tombokan X. Novel paradigm for immunotherapy of ovary cancer by engaging prophylactic immunity against hepatitis B. Clin Trans Med 2016; 5(44):1-16.

Lee MH, Sano K, Morales FE, Imagawa DT. Sensitive reverse transcriptase assay to detect and quantitate human immunodeficiency virus. J Clin Microbiol 1987; 25:1717-1721.

Gupta P, Balachandran R, Grovit K, Webster D, Rinaldo C Jr. Detection of human immunodeficiency virus by reverse transcriptase assay, antigen capture

assay, and radioimmunoassay. J Clin. Microbiol. 1987; 25:1122-1125.

Pyle SW1, Bess JW Jr, Robey WG, Fischinger PJ, Gilden RV, Arthur LO. Purification of 120,000 dalton envelope glycoprotein from culture fluids of human immunodeficiency virus (HIV)-infected H9 cells. AIDS Res Hum Retroviruses. 1987; 3(4):387-400.

Malecki M. HER2/neu gene expression products evaluated with superparamagnetic single chain variable fragment (scFv) antibodies. Proc S Dak Acad Sci. 2007; 86:297-308

Glazer JK, Malecki M, Grist TM. Targeted MRI Contrast Agent Using Bioengineered scFv Fragments with Gadolinium Labelled Metal Binding Domain. INSRM 2004; 12: 001713

S ö f f g e F, v o n H ö r s t e n W. A c - s u s c e p t i b i l i t y m e a s u r e m e n t s i n s m a l l f i e l d s o n f i n e superparamagnetic nickel particles. Zeitschrift für Physik B Condensed Matter. 1981; 42: 47–55.

Molday RS, Yen SPS, Rembaum A. Application of magnetic microspheres in labelling and separation of cells. Nature. 1977; 268: 437-438.

Malecki M, L’Vanne K, Truong L, Hsu A, Hogan C , A l b r e c h t R . S u p r a m o l e c u l a r I m a g i n g o f Immunolabeling with STEM EDX & EEL SI Microscopy and Microanalysis. 2004; 10(S02): 1216-1217.

Turkevich J, Stevenson PC, Hillier J. A study of the nucleation and growth processes in the synthesis of colloidal gold. Discussions of the Faraday Society. 1951; 11: 1-7.

Stöber W, Fink A, Bohn, E. Controlled growth of monodisperse silica spheres in the micron size range. Journal of Colloid and Interface Science. 1951; 26 (1): 62–69.

Krejcarek GE, Tucker KL. Covalent attachment of chelating groups to macromolecules. Biochem. Biophys. Res. Commun. 1977; 77(2): 581-585.

Meares CF, Goodwin DA, Leung CS, Girgis AY, Silvester DJ, Nunn AD, Lavender PJ. Covalent attachment of metal chelates to proteins: the stability in vivo and in vitro of the conjugate of albumin with a chelate of 111indium. Proc Natl Acad Sci U S A. 1976; 73(11): 3803-6.

How to Cite
Malecki, M., & Saetre, B. (2018). HIV Apheresis Tags (HIVAT) Aided Elimination of Viremia. <font Color="white">Molecular and Cellular Therapies</Font&gt;, 2018(1), 1-15.
Research Article