1 Wada N, Jacobson LP, Cohen M, French A, Phair J, Muñoz A. Cause-specific mortality among HIV-infected individuals, by CD4+ cell count at HAART initiation, compared with HIV-uninfected individuals. AIDS 2014; 28: 257–265.
2 F J Palella Jr, K M Delaney, A C Moorman, M O Loveless, J Fuhrer, G A Satten, D J Aschman SDH. Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection. N Engl J Med 2009; 338. doi:10.1056/NEJM199803263381301.
3 Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE et al. Identification of a Reservoir for HIV-1 in Patients on Highly Active Antiretroviral Therapy. Science (80- ) 1997; 278: 1295–1300.
4 Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nat 1997 3876629 1997; 387: 183–188.
5 Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K, Ho S et al. The Nature of the Principal Type 1 Interferon-Producing Cells in Human Blood. Science (80- ) 1999; 284: 1835–1837.
6 Bam RA, Hansen D, Irrinki A, Mulato A, Jones GS, Hesselgesser J et al. TLR7 Agonist GS-9620 Is a Potent Inhibitor of Acute HIV-1 Infection in Human Peripheral Blood Mononuclear Cells. Antimicrob Agents Chemother 2017; 61. doi:10.1128/AAC.01369-16.
7 Jakobsen MR, Bak RO, Andersen A, Berg RK, Jensen SB, Jin T et al. IFI16 senses DNA forms of the lentiviral replication cycle and controls HIV-1 replication. Proc Natl Acad Sci U S A 2013; 110: E4571–E4580.
8 Hotter D, Sauter D, Kirchhoff F. Emerging role of the host restriction factor tetherin in viral immune sensing. J Mol Biol 2013; 425: 4956–4964.
9 Fitzgerald-Bocarsly P, Feng D. The role of type I interferon production by dendritic cells in host defense. Biochimie 2007; 89: 843–855.
10 Barblu L, MacHmach K, Gras C, Delfraissy JF, Boufassa F, Leal M et al. Plasmacytoid Dendritic Cells (pDCs) From HIV Controllers Produce Interferon-α and Differentiate Into Functional Killer pDCs Under HIV Activation. J Infect Dis 2012; 206: 790–801.
11 Machmach K, Leal M, Gras C, Viciana P, Genebat M, Franco E et al. Plasmacytoid Dendritic Cells Reduce HIV Production in Elite Controllers. J Virol 2012; : 4245–4252.
12 Dominguez-Molina B, Machmach K, Perales C, Tarancon-Diez L, Gallego I, Sheldon JL et al. Toll-Like Receptor 7 (TLR-7) and TLR-9 Agonists Improve Hepatitis C Virus Replication and Infectivity Inhibition by Plasmacytoid Dendritic Cells. 2018.
13 Buitendijk M, Eszterhas SK, Howell AL. Gardiquimod: a Toll-like receptor-7 agonist that inhibits HIV type 1 infection of human macrophages and activated T cells. AIDS Res Hum Retroviruses 2013; 29: 907–918.
14 Fosdick A, Zheng J, Pflanz S, Frey CR, Hesselgesser J, Halcomb RL et al. Pharmacokinetic and Pharmacodynamic Properties of GS-9620, a Novel Toll-Like Receptor 7 Agonist, Demonstrate Interferon-Stimulated Gene Induction without Detectable Serum Interferon at Low Oral Doses. J Pharmacol Exp Ther 2014; 348: 96–105.
15 Lim SY, Osuna CE, Hraber PT, Hesselgesser J, Gerold JM, Barnes TL et al. TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy. Sci Transl Med 2018; 10: PMID: 29720451 PMCID: PMC5973480 DOI: 10.1126/scit.
16 Borducchi EN, Liu J, Nkolola JP, Cadena AM, Yu W-H, Fischinger S et al. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys. Nature 2018; 563: 360–364.
17 SenGupta D, Brinson C, DeJesus E, Mills A, Shalit P, Guo S et al. The TLR7 agonist vesatolimod induced a modest delay in viral rebound in HIV controllers after cessation of antiretroviral therapy. Sci Transl Med 2021; 13. doi:10.1126/scitranslmed.abg3071.
18 Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392: 245–252.
19 Lei J, Yin X, Shang H, Jiang Y. IP-10 is highly involved in HIV infection. Cytokine 2019; 115: 97–103.
20 Sereti I, Krebs SJ, Phanuphak N, Fletcher JL, Slike B, Pinyakorn S et al. Persistent, Albeit Reduced, Chronic Inflammation in Persons Starting Antiretroviral Therapy in Acute HIV Infection. Clin Infect Dis 2017; 64: 124–131.
21 Sun Y, Xue J. Expression Profile and Biological Role of Immune Checkpoints in Disease Progression of HIV/SIV Infection. Viruses 2022; 14. doi:10.3390/v14030581.
22 Tenorio AR, Zheng Y, Bosch RJ, Krishnan S, Rodriguez B, Hunt PW et al. Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment. J Infect Dis 2014; 210: 1248–1259.
23 Boulware DR, Hullsiek KH, Puronen CE, Rupert A, Baker J V., French MA et al. Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death. J Infect Dis 2011; 203: 1637–1646.
24 Ho JE, Scherzer R, Hecht FM, Maka K, Selby V, Martin JN et al. The Association of CD4+ T-Cell Count on Cardiovascular Risk in Treated HIV Disease. AIDS 2012; 26: 1115–1120.
25 Kwa S, Kannanganat S, Nigam P, Siddiqui M, Shetty RD, Ansari A et al. Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques. Blood 2012; 118: 2763–2773.
26 Herbeuval JP, Nilsson J, Boasso A, Hardy AW, Kruhlak MJ, Anderson SA et al. Differential expression of IFN-α and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients. Proc Natl Acad Sci U S A 2006; 103: 7000.
27 Fromentin R, Bakeman W, Lawani MB, Khoury G, Hartogensis W, DaFonseca S et al. CD4+ T Cells Expressing PD-1, TIGIT and LAG-3 Contribute to HIV Persistence during ART. PLoS Pathog 2016; 12: 1–19 PMID: 27415008 PMCID: PMC4944956 DOI: 10.1371.
28 Pardons M, Baxter AE, Massanella M, Pagliuzza A, Fromentin R, Dufour C et al. Single-cell characterization and quantification of translation-competent viral reservoirs in treated and untreated HIV infection. PLoS Pathog 2019; 15: PMID: 30811499 PMCID: PMC6411230 DOI: 10.1371/jour.
29 Hurst J, Hoffmann M, Pace M, Williams JP, Thornhill J, Hamlyn E et al. Immunological biomarkers predict HIV-1 viral rebound after treatment interruption. Nat Commun 2015; 6: PMID: 26449164 PMCID: PMC4633715 DOI: 10.1038/ncom.
30 Wherry EJ. T cell exhaustion. Nat Immunol 2011 126 2011; 12: 492–499.
31 Jones RB, Ndhlovu LC, Barbour JD, Sheth PM, Jha AR, Long BR et al. Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection. 2008; 205. doi:10.1084/JEM.20081398.
32 Kassu A, Marcus RA, D’Souza MB, Kelly-McKnight EA, Golden-Mason L, Akkina R et al. Regulation of virus-specific CD4+ T cell function by multiple costimulatory receptors during chronic HIV infection. J Immunol 2010; 185: 3007–3018.
33 Fonteneau J-F, Larsson M, Beignon A-S, McKenna K, Dasilva I, Amara A et al. Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells. J Virol 2004; 78: 5223–5232.
34 Martinsen JT, Gunst JD, Højen JF, Tolstrup M, Søgaard OS. The Use of Toll-Like Receptor Agonists in HIV-1 Cure Strategies. Front Immunol 2020; 11: PMID: 32595636 PMCID: PMC7300204 DOI: 10.3389/fimm.
35 Riddler SA, Para M, Benson CA, Mills A, Ramgopal M, Dejesus E et al. Vesatolimod, a Toll-like Receptor 7 Agonist, Induces Immune Activation in Virally Suppressed Adults Living with Human Immunodeficiency Virus-1. Clin Infect Dis 2021; 72: E815–E824.
36 Vibholm L, Schleimann MH, Højen JF, Benfield T, Offersen R, Rasmussen K et al. Short-course toll-like receptor 9 agonist treatment impacts innate immunity and plasma viremia in individuals with human immunodeficiency virus infection. Clin Infect Dis 2017; 64: 1686–1695.
37 Vibholm LK, Konrad C V., Schleimann MH, Frattari G, Winckelmann A, Klastrup V et al. Effects of 24-week Toll-like receptor 9 agonist treatment in HIV type 1+ individuals. AIDS 2019; 33: 1315–1325.
38 Lubong Sabado R, O’Brien M, Subedi A, Qin L, Hu N, Taylor E et al. Evidence of dysregulation of dendritic cells in primary HIV infection. Blood 2010; 116: 3839–3852.
39 Schlaepfer E, Speck RF. TLR8 activates HIV from latently infected cells of myeloid-monocytic origin directly via the MAPK pathway and from latently infected CD4+ T cells indirectly via TNF-α. J Immunol 2011; 186: 4314–4324.
40 Dhamanage AS, Thakar MR, Paranjape RS. HIV-1-Mediated Suppression of IFN-α Production Is Associated with Inhibition of IRF-7 Translocation and PI3K/akt Pathway in Plasmacytoid Dendritic Cells. AIDS Res Hum Retroviruses 2019; 35: 40–48.
41 Casartelli N, Sourisseau M, Feldmann J, Guivel-Benhassine F, Mallet A. Tetherin Restricts Productive HIV-1 Cell-to-Cell Transmission. PLoS Pathog 2010; 6: 1000955.
42 Jolly C, Booth NJ, Neil SJD. Cell-Cell Spread of Human Immunodeficiency Virus Type 1 Overcomes Tetherin/BST-2-Mediated Restriction in T cells. J Virol 2010; 84: 12185–12199.
43 Bego MG, Côté É, Aschman N, Mercier J, Weissenhorn W, Cohen ÉA. Vpu Exploits the Cross-Talk between BST2 and the ILT7 Receptor to Suppress Anti-HIV-1 Responses by Plasmacytoid Dendritic Cells. PLoS Pathog 2015; 11. doi:10.1371/journal.ppat.1005024.
44 Jego G, Palucka AK, Blanck JP, Chalouni C, Pascual V, Banchereau J. Plasmacytoid Dendritic Cells Induce Plasma Cell Differentiation through Type I Interferon and Interleukin 6. Immunity 2003; 19: 225–234.
45 Megjugorac NJ, Young HA, Amrute SB, Olshalsky SL, Fitzgerald-Bocarsly P. Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells. J Leukoc Biol 2004; 75: PMID: 14742635 DOI: 10.1189/jlb.0603291.
46 Colonna M, Trinchieri G, Liu YJ. Plasmacytoid dendritic cells in immunity. Nat Immunol 2004; 5: 1219–1226.
47 Kamphuis E, Junt T, Waibler Z, Forster R, Kalinke U. Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia. Blood 2006; 108: 3253–3261.
48 Gota C, Calabrese L. Induction of clinical autoimmune disease by therapeutic interferon-alpha. Autoimmunity 2003; 36: 511–518.
49 Baenziger S, Heikenwalder M, Johansen P, Schlaepfer E, Hofer U, Miller RC et al. Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology. Blood 2009; 113: 377–388.
50 Cao W, Bover L. Signaling and ligand interaction of ILT7: receptor-mediated regulatory mechanisms for plasmacytoid dendritic cells. Immunol Rev 2010; 234: 163–176.
51 Cao W, Bover L, Cho M, Wen X, Hanabuchi S, Bao M et al. Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J Exp Med 2009; 206: 1603.
52 Mitchell D, Chintala S, Dey M. Plasmacytoid dendritic cell in immunity and cancer. J Neuroimmunol 2018; 322: 63–73.
53 Smallwood HS, Aquino VH, Ferhadian D, Lupfer C, Jakobsen MR, Van Der Sluis RM et al. Plasmacytoid Dendritic Cells as Cell-Based Therapeutics: A Novel Immunotherapy to Treat Human Immunodeficiency Virus Infection? Front Cell Infect Microbiol 2020; 1: 249.
54 Villadangos JA, Young L. Antigen-Presentation Properties of Plasmacytoid Dendritic Cells. Immunity 2008; 29: 352–361.
55 Isnard S, Hatton EX, Iannetta M, Guillerme J-B, Hosmalin A. Cell-Associated HIV Cross-Presentation by Plasmacytoid Dendritic Cells Is Potentiated by Noncognate CD8 + T Cell Preactivation. J Immunol 2021; 207: 15–22.
56 Benitez-Ribas D, Adema GJ, Winkels G, Klasen IS, Punt CJA, Figdor CG et al. Plasmacytoid dendritic cells of melanoma patients present exogenous proteins to CD4+ T cells after Fc gamma RII-mediated uptake. J Exp Med 2006; 203: 1629–1635.
57 Young LJ, Wilson NS, Schnorrer P, Proietto A, ten Broeke T, Matsuki Y et al. Differential MHC class II synthesis and ubiquitination confers distinct antigen-presenting properties on conventional and plasmacytoid dendritic cells. Nat Immunol 2008; 9: 1244–1252.
58 Tel J, Lambeck AJA, Cruz LJ, Tacken PJ, de Vries IJM, Figdor CG. Human plasmacytoid dendritic cells phagocytose, process, and present exogenous particulate antigen. J Immunol 2010; 184: 4276–4283.
59 Tsai A, Irrinki A, Kaur J, Cihlar T, Kukolj G, Sloan DD et al. Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy. J Virol 2017; 91: PMID: 28179531 PMCID: PMC5375698 DOI: 10.1128/JVI.
60 Ventura JD, Nkolola JP, Chandrashekar A, Borducchi EN, Liu J, Mercado NB et al. Therapeutic ef fi cacy of an Ad26 / MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques. npj vaccines 2022; : 1–8.
61 Ram, Renee R, Paul Duatschek, Nicolas Margot, Michael Abram, Romas Geleziunas, Joseph Hesselgesser CC. Activation of HIV-specific CD8+ T-cells from HIV+ donors by vesatolimod. Antivir Ther 2020; 25: 163–169.
62 Neil SJD, Zang T, Bieniasz PD. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 2008; 451: 425–430.
63 Sheehy AM, Gaddis NC, Choi JD, Malim MH. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 2002; 418: 646–650.
64 Stremlau M, Owens CM, Perron MJ, Kiessling M, Autissier P, Sodroski J. The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys. Nature 2004; 427: 848–853.
65 Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L et al. SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nat Immunol 2012; 13: 223–228.
66 Abdel-Mohsen M, Wang C, Strain MC, Lada SM, Deng X, Cockerham LR et al. Select Host Restriction Factors Are Associated with HIV Persistence During Antiretroviral Therapy. AIDS 2015; 29: 411–420.
67 Manches O, Frleta D, Bhardwaj N. Dendritic cells in progression and pathology of HIV infection. Trends Immunol 2014; 35: 114–122.
68 Ferrando-Martínez S, Casazza JP, Leal M, Machmach K, Ángeles Muñoz-Fernández M, Viciana P et al. Differential Gag-Specific Polyfunctional T Cell Maturation Patterns in HIV-1 Elite Controllers. J Virol 2012; 86: 3667–3674.
69 Pernas M, Tarancón-Diez L, Rodríguez-Gallego E, Gómez J, Prado JG, Casado C et al. Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection. J Virol 2018; 92: 1805–1822 PMID: 29212942 PMCID: PMC5809746 DOI: 10.