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Clinical Interventions in HIV Cure Research

Part of the Advances in Experimental Medicine and Biology book series (AEMB,volume 1075)

Abstract

Research over the past decade has resulted in a much-improved understanding of how and where HIV persists in patients on otherwise suppressive antiretroviral therapy (ART). It has become clear that the establishment of a latent infection in long-lived cells is the key barrier to curing HIV or allowing for sustained ART-free remission. Informed by in vitro and ex vivo studies, several therapeutic approaches aimed at depleting the pool of latently infected cells have been tested in small-scale experimental clinical trials including studies of ART intensification, genome editing, ART during acute/early infection and latency reversal. Many studies have focused on the use of latency-reversing agents (LRAs) to induce immune- or virus-mediated elimination of virus-producing cells. These trials have been instrumental in establishing safety and have shown that it is possible to impact the state HIV latency in patients on suppressive ART. However, administration of LRAs alone has thus far not demonstrated an effect on the frequency of latently infected cells or the time to virus rebound during analytical interruption of ART. More recently, there has been an enhanced focus on immune-based therapies in the onwards search for an HIV cure including therapeutic vaccines, toll-like receptor agonists, broadly neutralising antibodies, immune checkpoint inhibitors, interferon-α and interleukin therapy. In ongoing studies immunotherapy interventions are also tested in combination with latency reversal. In this chapter, the overall results of these clinical interventions ultimately aimed at a cure for HIV are presented and discussed.

Keywords

  • HIV cure
  • Clinical trials
  • Histone deacetylase inhibitors
  • Latency-reversing agents
  • Immunotherapy

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References

  • Abdel-Mohsen M, Deng X, Liegler T, Guatelli JC, Salama MS, Ghanem Hel D, Rauch A, Ledergerber B, Deeks SG, Gunthard HF, Wong JK, Pillai SK (2014) Effects of alpha interferon treatment on intrinsic anti-HIV-1 immunity in vivo. J Virol 88(1):763–767. https://doi.org/10.1128/JVI.02687-13

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Amancha PK, Hong JJ, Rogers K, Ansari AA, Villinger F (2013) In vivo blockade of the programmed cell death-1 pathway using soluble recombinant PD-1-Fc enhances CD4+ and CD8+ T cell responses but has limited clinical benefit. J Immunol 191(12):6060–6070. https://doi.org/10.4049/jimmunol.1302044

    CAS  CrossRef  PubMed  Google Scholar 

  • Ananworanich J, Schuetz A, Vandergeeten C, Sereti I, de Souza M, Rerknimitr R, Dewar R, Marovich M, van Griensven F, Sekaly R, Pinyakorn S, Phanuphak N, Trichavaroj R, Rutvisuttinunt W, Chomchey N, Paris R, Peel S, Valcour V, Maldarelli F, Chomont N, Michael N, Phanuphak P, Kim JH, Group RSS (2012) Impact of multi-targeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection. PLoS One 7 (3):e33948. doi:https://doi.org/10.1371/journal.pone.0033948

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Ananworanich J, Chomont N, Eller LA, Kroon E, Tovanabutra S, Bose M, Nau M, Fletcher JL, Tipsuk S, Vandergeeten C, O'Connell RJ, Pinyakorn S, Michael N, Phanuphak N, Robb ML, Rv, groups RSs (2016) HIV DNA set point is rapidly established in acute HIV infection and dramatically reduced by early ART. EBioMedicine 11:68–72. https://doi.org/10.1016/j.ebiom.2016.07.024

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • 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 (2008) Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells. AIDS 22(10):1131–1135

    CAS  CrossRef  PubMed  Google Scholar 

  • Archin NM, Espeseth A, Parker D, Cheema M, Hazuda D, Margolis DM (2009a) Expression of latent HIV induced by the potent HDAC inhibitor suberoylanilide hydroxamic acid. AIDS ResHum Retrovir 25(2):207–212

    CAS  CrossRef  Google Scholar 

  • Archin NM, Keedy KS, Espeseth A, Dang H, Hazuda DJ, Margolis DM (2009b) Expression of latent human immunodeficiency type 1 is induced by novel and selective histone deacetylase inhibitors. AIDS 23(14):1799–1806

    CAS  CrossRef  PubMed  Google Scholar 

  • Archin NM, Cheema M, Parker D, Wiegand A, Bosch RJ, Coffin JM, Eron J, Cohen M, Margolis DM (2010) Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection. PLoSOne 5(2):e9390

    CrossRef  Google Scholar 

  • Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature. 2012;487(7408):482–5

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • 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 (2012a) Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487(7408):482–485. https://doi.org/10.1038/nature11286

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Archin NM, Vaidya NK, Kuruc JD, Liberty AL, Wiegand A, Kearney MF, Cohen MS, Coffin JM, Bosch RJ, Gay CL, Eron JJ, Margolis DM, Perelson AS (2012b) Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection. Proc Natl Acad Sci U S A 109(24):9523–9528. https://doi.org/10.1073/pnas.1120248109

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Archin NM, Bateson R, Tripathy M, 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 (2014) HIV-1 expression within resting CD4 T-cells following multiple doses of Vorinostat. J Infect Dis. https://doi.org/10.1093/infdis/jiu155

    CAS  CrossRef  Google Scholar 

  • Avettand-Fenoel V, Mahlaoui N, Chaix ML, Milliancourt C, Burgard M, Cavazzana-Calvo M, Rouzioux C, Blanche S (2007) Failure of bone marrow transplantation to eradicate HIV reservoir despite efficient HAART. AIDS 21(6):776–777. https://doi.org/10.1097/QAD.0b013e3280b01836

    CrossRef  PubMed  Google Scholar 

  • Azzoni L, Foulkes AS, Papasavvas E, Mexas AM, Lynn KM, Mounzer K, Tebas P, Jacobson JM, Frank I, Busch MP, Deeks SG, Carrington M, O'Doherty U, Kostman J, Montaner LJ (2013) Pegylated interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration. J Infect Dis 207(2):213–222. https://doi.org/10.1093/infdis/jis663

    CAS  CrossRef  PubMed  Google Scholar 

  • Banga R, Procopio FA, Noto A, Pollakis G, Cavassini M, Ohmiti K, Corpataux JM, de Leval L, Pantaleo G, Perreau M (2016) PD-1 and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals. Nat Med. https://doi.org/10.1038/nm.4113

    CAS  CrossRef  PubMed  Google Scholar 

  • Borrow P, Lewicki H, Wei X, Horwitz MS, Peffer N, Meyers H, Nelson JA, Gairin JE, Hahn BH, Oldstone MB, Shaw GM (1997) Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med 3(2):205–211

    CAS  CrossRef  PubMed  Google Scholar 

  • Boutros C, Tarhini A, Routier E, Lambotte O, Ladurie FL, Carbonnel F, Izzeddine H, Marabelle A, Champiat S, Berdelou A, Lanoy E, Texier M, Libenciuc C, Eggermont AM, Soria JC, Mateus C, Robert C (2016) Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol. https://doi.org/10.1038/nrclinonc.2016.58

    CAS  CrossRef  PubMed  Google Scholar 

  • Bruel T, Guivel-Benhassine F, Amraoui S, Malbec M, Richard L, Bourdic K, Donahue DA, Lorin V, Casartelli N, Noel N, Lambotte O, Mouquet H, Schwartz O (2016) Elimination of HIV-1-infected cells by broadly neutralizing antibodies. Nat Commun 7:10844. https://doi.org/10.1038/ncomms10844

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Buitendijk M, Eszterhas SK, Howell AL (2014) Toll-like receptor agonists are potent inhibitors of human immunodeficiency virus-type 1 replication in peripheral blood mononuclear cells. AIDS Res Hum Retrovir 30(5):457–467. https://doi.org/10.1089/AID.2013.0199

    CAS  CrossRef  PubMed  Google Scholar 

  • Bullen CK, Laird GM, Durand CM, Siliciano JD, Siliciano RF (2014) New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo. Nat Med 20(4):425–429. https://doi.org/10.1038/nm.3489

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Buzon MJ, Massanella M, Llibre JM, Esteve A, Dahl V, Puertas MC, Gatell JM, Domingo P, Paredes R, Sharkey M, Palmer S, Stevenson M, Clotet B, Blanco J, Martinez-Picado J (2010) HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med 16(4):460–465. https://doi.org/10.1038/nm.2111

    CAS  CrossRef  PubMed  Google Scholar 

  • Buzon MJ, Martin-Gayo E, Pereyra F, Ouyang Z, Sun H, Li JZ, Piovoso M, Shaw A, Dalmau J, Zangger N, Martinez-Picado J, Zurakowski R, Yu XG, Telenti A, Walker BD, Rosenberg ES, Lichterfeld M (2014) Long-term antiretroviral treatment initiated at primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir of HIV-1-infected CD4 T cells. J Virol 88(17):10056–10065. https://doi.org/10.1128/JVI.01046-14

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Chew GM, Fujita T, Webb GM, Burwitz BJ, Wu HL, Reed JS, Hammond KB, Clayton KL, Ishii N, Abdel-Mohsen M, Liegler T, Mitchell BI, Hecht FM, Ostrowski M, Shikuma CM, Hansen SG, Maurer M, Korman AJ, Deeks SG, Sacha JB, Ndhlovu LC (2016) TIGIT marks exhausted T cells, correlates with disease progression, and serves as a target for immune restoration in HIV and SIV infection. PLoS Pathog 12(1):e1005349. https://doi.org/10.1371/journal.ppat.1005349

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • 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 (2009) HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. NatMed 15(8):893–900

    CAS  Google Scholar 

  • Chun TW, Finzi D, Margolick J, Chadwick K, Schwartz D, Siliciano RF (1995) In vivo fate of HIV-1-infected T cells: quantitative analysis of the transition to stable latency. NatMed 1(12):1284–1290

    CAS  Google Scholar 

  • 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 (1997a) Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387(6629):183–188

    CAS  CrossRef  PubMed  Google Scholar 

  • Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS (1997b) Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci USA 94(24):13193–13197

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Chun TW, Engel D, Berrey MM, Shea T, Corey L, Fauci AS (1998) Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection. Proc Natl Acad Sci U S A 95(15):8869–8873

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Chun TW, Davey RT, Jr., Engel D, Lane HC, Fauci AS (1999a) Re-emergence of HIV after stopping therapy. Nature 401 (6756):874-875. doi:https://doi.org/10.1038/44755

    CAS  CrossRef  PubMed  Google Scholar 

  • Chun TW, Engel D, Mizell SB, Hallahan CW, Fischette M, Park S, Davey RT, Jr., Dybul M, Kovacs JA, Metcalf JA, Mican JM, Berrey MM, Corey L, Lane HC, Fauci AS (1999b) Effect of interleukin-2 on the pool of latently infected, resting CD4+ T cells in HIV-1-infected patients receiving highly active anti-retroviral therapy. NatMed 5 (6):651-655

    CAS  CrossRef  PubMed  Google Scholar 

  • Chun TW, Justement JS, Murray D, Hallahan CW, Maenza J, Collier AC, Sheth PM, Kaul R, Ostrowski M, Moir S, Kovacs C, Fauci AS (2010) Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication. AIDS 24(18):2803–2808

    CrossRef  PubMed  Google Scholar 

  • Chun TW, Murray D, Justement JS, Blazkova J, Hallahan CW, Fankuchen O, Gittens K, Benko E, Kovacs C, Moir S, Fauci AS (2014) Broadly neutralizing antibodies suppress HIV in the persistent viral reservoir. Proc Natl Acad Sci U S A 111(36):13151–13156. https://doi.org/10.1073/pnas.1414148111

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Cillo AR, Krishnan S, McMahon DK, Mitsuyasu RT, Para MF, Mellors JW (2014) Impact of chemotherapy for HIV-1 related lymphoma on residual Viremia and cellular HIV-1 DNA in patients on suppressive antiretroviral therapy. PLoS One 9(3):e92118. https://doi.org/10.1371/journal.pone.0092118

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Cuevas JM, Geller R, Garijo R, Lopez-Aldeguer J, Sanjuan R (2015) Extremely high mutation rate of HIV-1 in vivo. PLoS Biol 13(9):e1002251. https://doi.org/10.1371/journal.pbio.1002251

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Dahabieh MS, Battivelli E, Verdin E (2015) Understanding HIV latency: the road to an HIV cure. Annu Rev Med 66:407–421. https://doi.org/10.1146/annurev-med-092112-152941

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Damouche A, Lazure T, Avettand-Fenoel V, Huot N, Dejucq-Rainsford N, Satie AP, Melard A, David L, Gommet C, Ghosn J, Noel N, Pourcher G, Martinez V, Benoist S, Bereziat V, Cosma A, Favier B, Vaslin B, Rouzioux C, Capeau J, Muller-Trutwin M, Dereuddre-Bosquet N, Le Grand R, Lambotte O, Bourgeois C (2015) Adipose tissue is a neglected viral reservoir and an inflammatory site during chronic HIV and SIV infection. PLoS Pathog 11(9):e1005153. https://doi.org/10.1371/journal.ppat.1005153

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Darcis G, Kula A, Bouchat S, Fujinaga K, Corazza F, Ait-Ammar A, Delacourt N, Melard A, Kabeya K, Vanhulle C, Van Driessche B, Gatot JS, Cherrier T, Pianowski LF, Gama L, Schwartz C, Vila J, Burny A, Clumeck N, Moutschen M, De Wit S, Peterlin BM, Rouzioux C, Rohr O, Van Lint C (2015) An in-depth comparison of latency-reversing agent combinations in various in vitro and ex vivo HIV-1 latency models identified Bryostatin-1+JQ1 and Ingenol-B+JQ1 to potently reactivate viral gene expression. PLoS Pathog 11(7):e1005063. https://doi.org/10.1371/journal.ppat.1005063

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Davey RT Jr, Bhat N, Yoder C, Chun TW, Metcalf JA, Dewar R, Natarajan V, Lempicki RA, Adelsberger JW, Miller KD, Kovacs JA, Polis MA, Walker RE, Falloon J, Masur H, Gee D, Baseler M, Dimitrov DS, Fauci AS, Lane HC (1999) HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci USA 96(26):15109–15114

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, Mackey EW, Miller JD, Leslie AJ, DePierres C, Mncube Z, Duraiswamy J, Zhu B, Eichbaum Q, Altfeld M, Wherry EJ, Coovadia HM, Goulder PJ, Klenerman P, Ahmed R, Freeman GJ, Walker BD (2006) PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443(7109):350–354. https://doi.org/10.1038/nature05115

    CAS  CrossRef  PubMed  Google Scholar 

  • Deeks SG (2012) HIV: shock and kill. Nature 487(7408):439–440. https://doi.org/10.1038/487439a

    CAS  CrossRef  PubMed  Google Scholar 

  • Deeks SG, Lewin SR, Havlir DV (2013) The end of AIDS: HIV infection as a chronic disease. Lancet 382(9903):1525–1533. https://doi.org/10.1016/S0140-6736(13)61809-7

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA, Shan L, Siliciano RF (2015) Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 517(7534):381–385. https://doi.org/10.1038/nature14053

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • 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, Mican JM, Rehm CA, Coffin JM, Mellors JW, Siliciano RF, Maldarelli F (2009) Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci USA 106(23):9403–9408

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Doyon G, Zerbato J, Mellors JW, Sluis-Cremer N (2012) Disulfiram reactivates latent HIV-1 expression through depletion of the phosphatase and tensin homolog (PTEN). AIDS. https://doi.org/10.1097/QAD.0b013e3283570620

    CAS  CrossRef  PubMed  Google Scholar 

  • Dybul M, Hidalgo B, Chun TW, Belson M, Migueles SA, Justement JS, Herpin B, Perry C, Hallahan CW, Davey RT, Metcalf JA, Connors M, Fauci AS (2002) Pilot study of the effects of intermittent interleukin-2 on human immunodeficiency virus (HIV)-specific immune responses in patients treated during recently acquired HIV infection. JInfect Dis 185(1):61–68

    CAS  CrossRef  Google Scholar 

  • Eigentler TK, Hassel JC, Berking C, Aberle J, Bachmann O, Grunwald V, Kahler KC, Loquai C, Reinmuth N, Steins M, Zimmer L, Sendl A, Gutzmer R (2016) Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev 45:7–18. https://doi.org/10.1016/j.ctrv.2016.02.003

    CAS  CrossRef  PubMed  Google Scholar 

  • Eisele E, Siliciano RF (2012) Redefining the viral reservoirs that prevent HIV-1 eradication. Immunity 37(3):377–388. https://doi.org/10.1016/j.immuni.2012.08.010

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • El-Far M, Ancuta P, Routy JP, Zhang Y, Bakeman W, Bordi R, DaFonseca S, Said EA, Gosselin A, Tep TS, Eichbaum Q, van Grevenynghe J, Schwartz O, Freeman GJ, Haddad EK, Chomont N, Sekaly RP (2015) Nef promotes evasion of human immunodeficiency virus type 1-infected cells from the CTLA-4-mediated inhibition of T-cell activation. J Gen Virol 96 (Pt 6):1463-1477. doi:https://doi.org/10.1099/vir.0.000065

    CAS  CrossRef  Google Scholar 

  • 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 (2014) Activation of HIV transcription with short-course Vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog 10(10):e1004473. https://doi.org/10.1371/journal.ppat.1004473

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Elliott JH, McMahon JH, Chang CC, Lee SA, Hartogensis W, Bumpus N, Savic R, Roney J, Hoh R, Solomon A, Piatak M, Gorelick RJ, Lifson J, Bacchetti P, Deeks SG, Lewin SR (2015) Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV 2(12):e520–e529. https://doi.org/10.1016/S2352-3018(15)00226-X

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, Fatkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, Losso M, Markowitz N, Neuhaus J, Phillips A, Rappoport C (2006) CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 355(22):2283–2296

    CAS  CrossRef  PubMed  Google Scholar 

  • Falkenberg KJ, Johnstone RW (2014) Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov 13(9):673–691. https://doi.org/10.1038/nrd4360

    CAS  CrossRef  PubMed  Google Scholar 

  • 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 (1997) Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278(5341):1295–1300

    CAS  CrossRef  PubMed  Google Scholar 

  • Fletcher CV, Staskus K, Wietgrefe SW, Rothenberger M, Reilly C, Chipman JG, Beilman GJ, Khoruts A, Thorkelson A, Schmidt TE, Anderson J, Perkey K, Stevenson M, Perelson AS, Douek DC, Haase AT, Schacker TW (2014) Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A 111(6):2307–2312. https://doi.org/10.1073/pnas.1318249111

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Fukazawa Y, Lum R, Okoye AA, Park H, Matsuda K, Bae JY, Hagen SI, Shoemaker R, Deleage C, Lucero C, Morcock D, Swanson T, Legasse AW, Axthelm MK, Hesselgesser J, Geleziunas R, Hirsch VM, Edlefsen PT, Piatak M, Jr., Estes JD, Lifson JD, Picker LJ (2015) B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat Med 21 (2):132-139. doi:https://doi.org/10.1038/nm.3781

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Gaj T, Sirk SJ, Shui SL, Liu J (2016) Genome-editing technologies: principles and applications. Cold Spring Harb Perspect Biol 8(12). https://doi.org/10.1101/cshperspect.a023754

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • 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 (2010) The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial. PLoSMed 7(8)

    Google Scholar 

  • Gandhi RT, Coombs RW, Chan ES, Bosch RJ, Zheng L, Margolis DM, Read S, Kallungal B, Chang M, Goecker EA, Wiegand A, Kearney M, Jacobson JM, D'Aquila R, Lederman MM, Mellors JW, Eron JJ (2012) No effect of raltegravir intensification on viral replication markers in the blood of HIV-1-infected patients receiving antiretroviral therapy. J Acquir Immune Defic Syndr 59(3):229–235. https://doi.org/10.1097/QAI.0b013e31823fd1f2

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Gianella S, von Wyl V, Fischer M, Niederoest B, Battegay M, Bernasconi E, Cavassini M, Rauch A, Hirschel B, Vernazza P, Weber R, Joos B, Gunthard HF, Swiss HIVCS (2011) Effect of early antiretroviral therapy during primary HIV-1 infection on cell-associated HIV-1 DNA and plasma HIV-1 RNA. Antivir Ther 16(4):535–545. https://doi.org/10.3851/IMP1776

    CAS  CrossRef  PubMed  Google Scholar 

  • Goulder PJ, Walker BD (2012) HIV and HLA class I: an evolving relationship. Immunity 37(3):426–440. https://doi.org/10.1016/j.immuni.2012.09.005

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Gutierrez C, Diaz L, Vallejo A, Hernandez-Novoa B, Abad M, Madrid N, Dahl V, Rubio R, Moreno AM, Dronda F, Casado JL, Navas E, Perez-Elias MJ, Zamora J, Palmer S, Munoz E, Munoz-Fernandez MA, Moreno S (2011) Intensification of antiretroviral therapy with a CCR5 antagonist in patients with chronic HIV-1 infection: effect on T cells latently infected. PLoS One 6(12):e27864. https://doi.org/10.1371/journal.pone.0027864

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Gutierrez C, Serrano-Villar S, Madrid-Elena N, Perez-Elias MJ, Martin ME, Barbas C, Ruiperez J, Munoz E, Munoz-Fernandez MA, Castor T, Moreno S (2016) Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy. AIDS 30(9):1385–1392. https://doi.org/10.1097/QAD.0000000000001064

    CAS  CrossRef  PubMed  Google Scholar 

  • Hatano H, Hayes TL, Dahl V, Sinclair E, Lee TH, Hoh R, Lampiris H, Hunt PW, Palmer S, McCune JM, Martin JN, Busch MP, Shacklett BL, Deeks SG (2011) A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. J Infect Dis 203(7):960–968. https://doi.org/10.1093/infdis/jiq138

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Hatano H, Strain MC, Scherzer R, Bacchetti P, Wentworth D, Hoh R, Martin JN, McCune JM, Neaton JD, Tracy RP, Hsue PY, Richman DD, Deeks SG (2013) Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV infection: a randomized, placebo-controlled trial. J Infect Dis 208(9):1436–1442. https://doi.org/10.1093/infdis/jit453

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Henrich TJ, Hu Z, Li JZ, Sciaranghella G, Busch MP, Keating SM, Gallien S, Lin NH, Giguel FF, Lavoie L, Ho VT, Armand P, Soiffer RJ, Sagar M, Lacasce AS, Kuritzkes DR (2013) Long-term reduction in peripheral blood HIV type 1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation. J Infect Dis 207(11):1694–1702. https://doi.org/10.1093/infdis/jit086

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Henrich TJ, Hanhauser E, Marty FM, Sirignano MN, Keating S, Lee TH, Robles YP, Davis BT, Li JZ, Heisey A, Hill AL, Busch MP, Armand P, Soiffer RJ, Altfeld M, Kuritzkes DR (2014) Antiretroviral-free HIV-1 remission and viral rebound after Allogeneic stem cell transplantation: report of 2 cases. Ann Intern Med. https://doi.org/10.7326/M14-1027

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Hersperger AR, Pereyra F, Nason M, Demers K, Sheth P, Shin LY, Kovacs CM, Rodriguez B, Sieg SF, Teixeira-Johnson L, Gudonis D, Goepfert PA, Lederman MM, Frank I, Makedonas G, Kaul R, Walker BD, Betts MR (2010) Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control. PLoS Pathog 6(5):e1000917. https://doi.org/10.1371/journal.ppat.1000917

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Hutter G (2014) More on shift of HIV tropism in stem-cell transplantation with CCR5 delta32/delta32 mutation. N Engl J Med 371(25):2437–2438. https://doi.org/10.1056/NEJMc1412279#SA1

    CrossRef  PubMed  Google Scholar 

  • Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K, Schneider T, Hofmann J, Kucherer C, Blau O, Blau IW, Hofmann WK, Thiel E (2009) Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 360(7):692–698. https://doi.org/10.1056/NEJMoa0802905

    CrossRef  PubMed  Google Scholar 

  • Imamichi H, Degray G, Asmuth DM, Fischl MA, Landay AL, Lederman MM, Sereti I (2011) HIV-1 viruses detected during episodic blips following interleukin-7 administration are similar to the viruses present before and after interleukin-7 therapy. AIDS 25(2):159–164. https://doi.org/10.1097/QAD.0b013e328340a270

    CAS  CrossRef  PubMed  Google Scholar 

  • Investigators ST, Fidler S, Porter K, Ewings F, Frater J, Ramjee G, Cooper D, Rees H, Fisher M, Schechter M, Kaleebu P, Tambussi G, Kinloch S, Miro JM, Kelleher A, McClure M, Kaye S, Gabriel M, Phillips R, Weber J, Babiker A (2013) Short-course antiretroviral therapy in primary HIV infection. N Engl J Med 368(3):207–217. https://doi.org/10.1056/NEJMoa1110039

    CAS  CrossRef  Google Scholar 

  • Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5(10):987–995. https://doi.org/10.1038/ni1112

    CAS  CrossRef  PubMed  Google Scholar 

  • Jain V, Hartogensis W, Bacchetti P, Hunt PW, Hatano H, Sinclair E, Epling L, Lee TH, Busch MP, McCune JM, Pilcher CD, Hecht FM, Deeks SG (2013) Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size. J Infect Dis 208(8):1202–1211. https://doi.org/10.1093/infdis/jit311

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Jones RB, Mueller S, O'Connor R, Rimpel K, Sloan DD, Karel D, Wong HC, Jeng EK, Thomas AS, Whitney JB, Lim SY, Kovacs C, Benko E, Karandish S, Huang SH, Buzon MJ, Lichterfeld M, Irrinki A, Murry JP, Tsai A, Yu H, Geleziunas R, Trocha A, Ostrowski MA, Irvine DJ, Walker BD (2016) A subset of latency-reversing agents expose HIV-infected resting CD4+ T-cells to recognition by cytotoxic T-lymphocytes. PLoS Pathog 12(4):e1005545. https://doi.org/10.1371/journal.ppat.1005545

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Kanzler H, Barrat FJ, Hessel EM, Coffman RL (2007) Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nat Med 13(5):552–559. https://doi.org/10.1038/nm1589

    CAS  CrossRef  PubMed  Google Scholar 

  • Katlama C, Lambert-Niclot S, Assoumou L, Papagno L, Lecardonnel F, Zoorob R, Tambussi G, Clotet B, Youle M, Achenbach CJ, Murphy RL, Calvez V, Costagliola D, Autran B, EraMune-01 study t (2016) Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial. AIDS 30(2):221–230. https://doi.org/10.1097/QAD.0000000000000894

    CAS  CrossRef  PubMed  Google Scholar 

  • Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on toll-like receptors. Nat Immunol 11(5):373–384. https://doi.org/10.1038/ni.1863

    CAS  CrossRef  PubMed  Google Scholar 

  • Kordelas L, Verheyen J, Beelen DW, Horn PA, Heinold A, Kaiser R, Trenschel R, Schadendorf D, Dittmer U, Esser S, Essen HIVAG (2014) Shift of HIV tropism in stem-cell transplantation with CCR5 Delta32 mutation. N Engl J Med 371(9):880–882. https://doi.org/10.1056/NEJMc1405805

    CrossRef  PubMed  Google Scholar 

  • Krieg AM (2006) Therapeutic potential of Toll-like receptor 9 activation. NatRevDrug Discov 5(6):471–484

    CAS  CrossRef  Google Scholar 

  • Krieg AM (2007) Development of TLR9 agonists for cancer therapy. J Clin Invest 117(5):1184–1194. https://doi.org/10.1172/JCI31414

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Kulkosky J, Culnan DM, Roman J, Dornadula G, Schnell M, Boyd MR, Pomerantz RJ (2001) Prostratin: activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART. Blood 98(10):3006–3015

    CAS  CrossRef  PubMed  Google Scholar 

  • Kuritzkes DR (2016) Hematopoietic stem cell transplantation for HIV cure. J Clin Invest 126(2):432–437. https://doi.org/10.1172/JCI80563

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, Yatim A, Emiliani S, Schwartz O, Benkirane M (2011) SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474(7353):654–657. https://doi.org/10.1038/nature10117

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Laird GM, Eisele EE, Rabi SA, Lai J, Chioma S, Blankson JN, Siliciano JD, Siliciano RF (2013) Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay. PLoS Pathog 9(5):e1003398. https://doi.org/10.1371/journal.ppat.1003398

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Laird GM, Bullen CK, Rosenbloom DI, Martin AR, Hill AL, Durand CM, Siliciano JD, Siliciano RF (2015) Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations. J Clin Invest 125(5):1901–1912. https://doi.org/10.1172/JCI80142

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Laubach JP, Moreau P, San-Miguel JF, Richardson PG (2015) Panobinostat for the treatment of multiple myeloma. Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-15-0530

    CAS  CrossRef  PubMed  Google Scholar 

  • Lehrman G, Ylisastigui L, Bosch RJ, Margolis DM (2004) Interleukin-7 induces HIV type 1 outgrowth from peripheral resting CD4+ T cells. J Acquir Immune Defic Syndr 36(5):1103–1104

    CrossRef  PubMed  Google Scholar 

  • 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 (2005) Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet 366(9485):549–555

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Leth S, Schleimann MH, Nissen SK, Hojen JF, Olesen R, Graversen ME, Jorgensen S, Kjaer AS, Denton PW, Mork A, Sommerfelt MA, Krogsgaard K, Ostergaard L, Rasmussen TA, Tolstrup M, Sogaard OS (2016) Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. Lancet HIV 3(10):e463–e472. https://doi.org/10.1016/S2352-3018(16)30055-8

    CrossRef  PubMed  Google Scholar 

  • Levy Y, Lacabaratz C, Weiss L, Viard JP, Goujard C, Lelievre JD, Boue F, Molina JM, Rouzioux C, Avettand-Fenoel V, Croughs T, Beq S, Thiebaut R, Chene G, Morre M, Delfraissy JF (2009) Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest 119(4):997–1007. https://doi.org/10.1172/JCI38052

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Levy Y, Sereti I, Tambussi G, Routy JP, Lelievre JD, Delfraissy JF, Molina JM, Fischl M, Goujard C, Rodriguez B, Rouzioux C, Avettand-Fenoel V, Croughs T, Beq S, Morre M, Poulin JF, Sekaly RP, Thiebaut R, Lederman MM (2012) Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebo-controlled, multicenter study. Clin Infect Dis 55(2):291–300. https://doi.org/10.1093/cid/cis383

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Li JZ, Smith DM, Mellors JW (2015) The need for treatment interruption studies and biomarker identification in the search for an HIV cure. AIDS 29(12):1429–1432. https://doi.org/10.1097/QAD.0000000000000658

    CrossRef  PubMed  Google Scholar 

  • Liu Y, Zeng G (2012) Cancer and innate immune system interactions: translational potentials for cancer immunotherapy. J Immunother 35(4):299–308. https://doi.org/10.1097/CJI.0b013e3182518e83

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Llibre JM, Buzon MJ, Massanella M, Esteve A, Dahl V, Puertas MC, Domingo P, Gatell JM, Larrouse M, Gutierrez M, Palmer S, Stevenson M, Blanco J, Martinez-Picado J, Clotet B (2012) Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: a randomized 48-week study. Antivir Ther 17(2):355–364. https://doi.org/10.3851/imp1917

    CAS  CrossRef  PubMed  Google Scholar 

  • Lorenzo-Redondo R, Fryer HR, Bedford T, Kim EY, Archer J, Kosakovsky Pond SL, Chung YS, Penugonda S, Chipman JG, Fletcher CV, Schacker TW, Malim MH, Rambaut A, Haase AT, McLean AR, Wolinsky SM (2016) Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature. https://doi.org/10.1038/nature16933

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Lu CL, Murakowski DK, Bournazos S, Schoofs T, Sarkar D, Halper-Stromberg A, Horwitz JA, Nogueira L, Golijanin J, Gazumyan A, Ravetch JV, Caskey M, Chakraborty AK, Nussenzweig MC (2016) Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science 352(6288):1001–1004. https://doi.org/10.1126/science.aaf1279

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Luzuriaga K, Gay H, Ziemniak C, Sanborn KB, Somasundaran M, Rainwater-Lovett K, Mellors JW, Rosenbloom D, Persaud D (2015) Viremic relapse after HIV-1 remission in a perinatally infected child. N Engl J Med 372(8):786–788. https://doi.org/10.1056/NEJMc1413931

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Lynch RM, Boritz E, Coates EE, DeZure A, Madden P, Costner P, Enama ME, Plummer S, Holman L, Hendel CS, Gordon I, Casazza J, Conan-Cibotti M, Migueles SA, Tressler R, Bailer RT, McDermott A, Narpala S, O'Dell S, Wolf G, Lifson JD, Freemire BA, Gorelick RJ, Pandey JP, Mohan S, Chomont N, Fromentin R, Chun TW, Fauci AS, Schwartz RM, Koup RA, Douek DC, Hu Z, Capparelli E, Graham BS, Mascola JR, Ledgerwood JE, Team VRCS (2015) Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci Transl Med 7(319):319ra206. https://doi.org/10.1126/scitranslmed.aad5752

    CAS  CrossRef  PubMed  Google Scholar 

  • Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R (2007) FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist 12(10):1247–1252. https://doi.org/10.1634/theoncologist.12-10-1247

    CAS  CrossRef  PubMed  Google Scholar 

  • Martin GE, Gossez M, Williams JP, Stohr W, Meyerowitz J, Leitman EM, Goulder P, Porter K, Fidler S, Frater J, and the STI (2017) Post-treatment control or treated controllers? Viral remission in treated and untreated primary HIV infection. AIDS 31(4):477–484. https://doi.org/10.1097/QAD.0000000000001382

    CAS  CrossRef  PubMed  Google Scholar 

  • Matalon S, Palmer BE, Nold MF, Furlan A, Kassu A, Fossati G, Mascagni P, Dinarello CA (2010) The histone deacetylase inhibitor ITF2357 decreases surface CXCR4 and CCR5 expression on CD4(+) T-cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro. J Acquir Immune Defic Syndr 54(1):1–9

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • McMahon D, Jones J, Wiegand A, Gange SJ, Kearney M, Palmer S, McNulty S, Metcalf JA, Acosta E, Rehm C, Coffin JM, Mellors JW, Maldarelli F (2010) 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 50(6):912–919

    CAS  CrossRef  PubMed  Google Scholar 

  • Minucci S, Pelicci PG (2006) Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 6(1):38–51. https://doi.org/10.1038/nrc1779

    CAS  CrossRef  PubMed  Google Scholar 

  • Moron-Lopez S, Gomez-Mora E, Salgado M, Ouchi D, Puertas MC, Urrea V, Navarro J, Jou A, Perez M, Tural C, Clotet B, Montaner LJ, Blanco J, Crespo M, Martinez-Picado J (2016) Short-term treatment with interferon Alfa diminishes expression of HIV-1 and reduces CD4+ T-cell activation in patients Coinfected with HIV and hepatitis C virus and receiving antiretroviral therapy. J Infect Dis 213(6):1008–1012. https://doi.org/10.1093/infdis/jiv521

    CAS  CrossRef  PubMed  Google Scholar 

  • Mota TM, Rasmussen TA, Rhodes A, Tennakoon S, Dantanarayana A, Wightman F, Hagenauer M, Roney J, Spelman T, Purcell DF, McMahon J, Hoy JF, Prince HM, Elliott JH, Lewin SR (2017) No adverse safety or virological changes two years following vorinostat in HIV-infected individuals on antiretroviral therapy. AIDS. https://doi.org/10.1097/QAD.0000000000001442

    CAS  CrossRef  PubMed  Google Scholar 

  • Mothe B, Molto J, Manzardo C, Coll J, Puertas MC, Martinez-Picado J, Hanke T, Clotet B, Brander C (2017) Viral control induced by HIVconsv vaccines and romidepsin in early treated individuals. Paper presented at the Conference on retroviruses and opportunistic infections, Seattle, USA

    Google Scholar 

  • Nishimura Y, Gautam R, Chun TW, Sadjadpour R, Foulds KE, Shingai M, Klein F, Gazumyan A, Golijanin J, Donaldson M, Donau OK, Plishka RJ, Buckler-White A, Seaman MS, Lifson JD, Koup RA, Fauci AS, Nussenzweig MC, Martin MA (2017) Early antibody therapy can induce long-lasting immunity to SHIV. Nature. https://doi.org/10.1038/nature21435

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Offersen R, Nissen SK, Rasmussen TA, Ostergaard L, Denton PW, Sogaard OS, Tolstrup M (2016) A novel toll-like receptor 9 agonist, MGN1703, enhances HIV-1 transcription and NK cell-mediated inhibition of HIV-1-infected autologous CD4+ T cells. J Virol 90(9):4441–4453. https://doi.org/10.1128/JVI.00222-16

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Olesen R, Vigano S, Rasmussen T, Sogaard OS, Ouyang Z, Buzon M, Bashirova A, Carrington M, Palmer S, Brinkmann CR, Yu XG, Ostergaard L, Tolstrup M, Lichterfeld M (2015) Innate immune activity correlates with CD4 T cell-associated HIV-1 DNA decline during latency-reversing treatment with panobinostat. J Virol. https://doi.org/10.1128/JVI.01484-15

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Pallikkuth S, Sharkey M, Babic DZ, Gupta S, Stone GW, Fischl MA, Stevenson M, Pahwa S (2015) Peripheral T follicular helper cells are the major HIV reservoir within central memory CD4 T cells in peripheral blood from chronically HIV-infected individuals on combination antiretroviral therapy. J Virol 90(6):2718–2728. https://doi.org/10.1128/JVI.02883-15

    CAS  CrossRef  PubMed  Google Scholar 

  • Park J, Kwon M, Shin EC (2016) Immune checkpoint inhibitors for cancer treatment. Arch Pharm Res 39(11):1577–1587. https://doi.org/10.1007/s12272-016-0850-5

    CAS  CrossRef  PubMed  Google Scholar 

  • Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, Saksela K, Markowitz M, Ho DD (1997) Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 387(6629):188–191. https://doi.org/10.1038/387188a0

    CAS  CrossRef  PubMed  Google Scholar 

  • Persaud D, Luzuriaga K (2014) Absence of HIV-1 after treatment cessation in an infant. N Engl J Med 370(7):678. https://doi.org/10.1056/NEJMc1315498

    CrossRef  PubMed  Google Scholar 

  • Plimack ER, Tan T, Wong YN, von Mehren MM, Malizzia L, Roethke SK, Litwin S, Li T, Hudes GR, Haas NB (2014) A phase I study of temsirolimus and bryostatin-1 in patients with metastatic renal cell carcinoma and soft tissue sarcoma. Oncologist 19(4):354–355. https://doi.org/10.1634/theoncologist.2014-0020

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Porichis F, Kaufmann DE (2012) Role of PD-1 in HIV pathogenesis and as target for therapy. Curr HIV/AIDS Rep 9(1):81–90. https://doi.org/10.1007/s11904-011-0106-4

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Porichis F, Kwon DS, Zupkosky J, Tighe DP, McMullen A, Brockman MA, Pavlik DF, Rodriguez-Garcia M, Pereyra F, Freeman GJ, Kavanagh DG, Kaufmann DE (2011) Responsiveness of HIV-specific CD4 T cells to PD-1 blockade. Blood 118(4):965–974. https://doi.org/10.1182/blood-2010-12-328070

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor D, Salama AK, Taylor M, Ott PA, Rollin LM, Horak C, Gagnier P, Wolchok JD, Hodi FS (2015) Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 372(21):2006–2017. https://doi.org/10.1056/NEJMoa1414428

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Procopio FA, Fromentin R, Kulpa DA, Brehm JH, Bebin AG, Strain MC, Richman DD, O'Doherty U, Palmer S, Hecht FM, Hoh R, Barnard RJ, Miller MD, Hazuda DJ, Deeks SG, Sekaly RP, Chomont N (2015) A novel assay to measure the magnitude of the inducible viral reservoir in HIV-infected individuals. EBioMedicine 2(8):872–881. https://doi.org/10.1016/j.ebiom.2015.06.019

    CrossRef  Google Scholar 

  • Ramsdell JS, Pettit GR, Tashjian AH Jr (1986) Three activators of protein kinase C, bryostatins, dioleins, and phorbol esters, show differing specificities of action on GH4 pituitary cells. J Biol Chem 261(36):17073–17080

    CAS  PubMed  Google Scholar 

  • Rasmussen TA, Lewin SR (2016) Shocking HIV out of hiding: where are we with clinical trials of latency reversing agents? Curr Opin HIV AIDS. https://doi.org/10.1097/COH.0000000000000279

    CAS  CrossRef  PubMed  Google Scholar 

  • Rasmussen TA, Schmeltz Sogaard O, Brinkmann C, Wightman F, Lewin SR, Melchjorsen J, Dinarello C, Ostergaard L, Tolstrup M (2013) Comparison of HDAC inhibitors in clinical development: effect on HIV production in latently infected cells and T-cell activation. Hum Vaccin Immunother 9(5):993–1001. https://doi.org/10.4161/hv.23800

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, Erikstrup C, Solomon A, Winckelmann A, Palmer S, Dinarello C, Buzon M, Lichterfeld M, Lewin SR, Ostergaard L, Sogaard OS (2014) Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV 1(1):e13–e21. https://doi.org/10.1016/S2352-3018(14)70014-1

    CrossRef  PubMed  Google Scholar 

  • Rasmussen TA, Tolstrup M, Sogaard OS (2016) Reversal of latency as part of a cure for HIV-1. Trends Microbiol 24(2):90–97. https://doi.org/10.1016/j.tim.2015.11.003

    CAS  CrossRef  PubMed  Google Scholar 

  • Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbe C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, Ascierto PA (2015a) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372(4):320–330. https://doi.org/10.1056/NEJMoa1412082

    CAS  CrossRef  PubMed  Google Scholar 

  • Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A, investigators K (2015b) Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med 372(26):2521–2532. https://doi.org/10.1056/NEJMoa1503093

    CAS  CrossRef  PubMed  Google Scholar 

  • Rothenberger MK, Keele BF, Wietgrefe SW, Fletcher CV, Beilman GJ, Chipman JG, Khoruts A, Estes JD, Anderson J, Callisto SP, Schmidt TE, Thorkelson A, Reilly C, Perkey K, Reimann TG, Utay NS, Nganou Makamdop K, Stevenson M, Douek DC, Haase AT, Schacker TW (2015) Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption. Proc Natl Acad Sci U S A 112(10):E1126–E1134. https://doi.org/10.1073/pnas.1414926112

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Routy JP, Tremblay CL, Angel JB, Trottier B, Rouleau D, Baril JG, Harris M, Trottier S, Singer J, Chomont N, Sekaly RP, Boulassel MR (2012) Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study. HIV Med 13(5):291–296. https://doi.org/10.1111/j.1468-1293.2011.00975.x

    CAS  CrossRef  PubMed  Google Scholar 

  • Rouzioux C, Hocqueloux L, Saez-Cirion A (2015) Posttreatment controllers: what do they tell us? Curr Opin HIV AIDS 10(1):29–34. https://doi.org/10.1097/COH.0000000000000123

    CAS  CrossRef  PubMed  Google Scholar 

  • Ruelas DS, Greene WC (2013) An integrated overview of HIV-1 latency. Cell 155(3):519–529. https://doi.org/10.1016/j.cell.2013.09.044

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Saez-Cirion A, Lacabaratz C, Lambotte O, Versmisse P, Urrutia A, Boufassa F, Barre-Sinoussi F, Delfraissy JF, Sinet M, Pancino G, Venet A, Agence Nationale de Recherches sur le Sida EPHIVCSG (2007) HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc Natl Acad Sci U S A 104(16):6776–6781. https://doi.org/10.1073/pnas.0611244104

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Saez-Cirion A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, Lecuroux C, Potard V, Versmisse P, Melard A, Prazuck T, Descours B, Guergnon J, Viard JP, Boufassa F, Lambotte O, Goujard C, Meyer L, Costagliola D, Venet A, Pancino G, Autran B, Rouzioux C, Group AVS (2013) Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI study. PLoS Pathog 9(3):e1003211. https://doi.org/10.1371/journal.ppat.1003211

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Scheller C, Ullrich A, McPherson K, Hefele B, Knoferle J, Lamla S, Olbrich AR, Stocker H, Arasteh K, ter MV, Rethwilm A, Koutsilieri E, Dittmer U (2004) CpG oligodeoxynucleotides activate HIV replication in latently infected human T cells. J Biol Chem 279(21):21897–21902

    CAS  CrossRef  PubMed  Google Scholar 

  • Scheller C, Ullrich A, Lamla S, Dittmer U, Rethwilm A, Koutsilieri E (2006) Dual activity of phosphorothioate CpG oligodeoxynucleotides on HIV: reactivation of latent provirus and inhibition of productive infection in human T cells. Ann NY Acad Sci 1091:540–547

    CAS  CrossRef  PubMed  Google Scholar 

  • Schildberg FA, Klein SR, Freeman GJ, Sharpe AH (2016) Coinhibitory pathways in the B7-CD28 ligand-receptor family. Immunity 44(5):955–972. https://doi.org/10.1016/j.immuni.2016.05.002

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • 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, Silvestri G, Lederman MM (2009) IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Blood 113(25):6304–6314. https://doi.org/10.1182/blood-2008-10-186601

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Shan L, Xing S, Yang HC, Zhang H, Margolick JB, Siliciano RF (2014) Unique characteristics of histone deacetylase inhibitors in reactivation of latent HIV-1 in Bcl-2-transduced primary resting CD4+ T cells. J Antimicrob Chemother 69(1):28–33. https://doi.org/10.1093/jac/dkt338

    CAS  CrossRef  PubMed  Google Scholar 

  • Shang HT, Ding JW, Yu SY, Wu T, Zhang QL, Liang FJ (2015) Progress and challenges in the use of latent HIV-1 reactivating agents. Acta Pharmacol Sin 36(8):908–916. https://doi.org/10.1038/aps.2015.22

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Sharma P, Allison JP (2015) Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell 161(2):205–214. https://doi.org/10.1016/j.cell.2015.03.030

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Siliciano RF, Greene WC (2011) HIV latency. Cold Spring Harb Perspect Med 1(1):a007096. https://doi.org/10.1101/cshperspect.a007096

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Simonetti FR, Sobolewski MD, Fyne E, Shao W, Spindler J, Hattori J, Anderson EM, Watters SA, Hill S, Wu X, Wells D, Su L, Luke BT, Halvas EK, Besson G, Penrose KJ, Yang Z, Kwan RW, Van Waes C, Uldrick T, Citrin DE, Kovacs J, Polis MA, Rehm CA, Gorelick R, Piatak M, Keele BF, Kearney MF, Coffin JM, Hughes SH, Mellors JW, Maldarelli F (2016) Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo. Proc Natl Acad Sci U S A 113(7):1883–1888. https://doi.org/10.1073/pnas.1522675113

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Sogaard OS, Graversen ME, Leth S, Olesen R, Brinkmann CR, Nissen SK, Kjaer AS, Schleimann MH, Denton PW, Hey-Cunningham WJ, Koelsch KK, Pantaleo G, Krogsgaard K, Sommerfelt M, Fromentin R, Chomont N, Rasmussen TA, Ostergaard L, Tolstrup M (2015) The depsipeptide Romidepsin reverses HIV-1 latency in vivo. PLoS Pathog 11(9):e1005142. https://doi.org/10.1371/journal.ppat.1005142

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Spivak AM, Andrade A, Eisele E, Hoh R, Bacchetti P, Bumpus NN, Emad F, Buckheit R 3rd, McCance-Katz EF, Lai J, Kennedy M, Chander G, Siliciano RF, Siliciano JD, Deeks SG (2014) A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy. Clin Infect Dis 58(6):883–890. https://doi.org/10.1093/cid/cit813

    CAS  CrossRef  PubMed  Google Scholar 

  • Stellbrink HJ, van LJ, Westby M, O'Sullivan E, Schneider C, Adam A, Weitner L, Kuhlmann B, Hoffmann C, Fenske S, Aries PS, Degen O, Eggers C, Petersen H, Haag F, Horst HA, Dalhoff K, Mocklinghoff C, Cammack N, Tenner-Racz K, Racz P (2002) Effects of interleukin-2 plus highly active antiretroviral therapy on HIV-1 replication and proviral DNA (COSMIC trial). AIDS 16(11):1479–1487

    CAS  CrossRef  PubMed  Google Scholar 

  • Strain MC, Little SJ, Daar ES, Havlir DV, Gunthard HF, Lam RY, Daly OA, Nguyen J, Ignacio CC, Spina CA, Richman DD, Wong JK (2005) Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1. J Infect Dis 191(9):1410–1418. https://doi.org/10.1086/428777

    CAS  CrossRef  PubMed  Google Scholar 

  • Sugarman J, Lewin SR, Henrich TJ, Rasmussen TA (2016) Ethics of ART interruption after stem-cell transplantation. Lancet HIV 3(1):e8–e10. https://doi.org/10.1016/S2352-3018(15)00248-9

    CrossRef  PubMed  Google Scholar 

  • Sun H, Buzon MJ, Shaw A, Berg RK, Yu XG, Ferrando-Martinez S, Leal M, Ruiz-Mateos E, Lichterfeld M (2014) Hepatitis C therapy with interferon-alpha and ribavirin reduces CD4 T-cell-associated HIV-1 DNA in HIV-1/hepatitis C virus-coinfected patients. J Infect Dis 209(9):1315–1320. https://doi.org/10.1093/infdis/jit628

    CAS  CrossRef  PubMed  Google Scholar 

  • Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine BL, June CH (2014) Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 370(10):901–910. https://doi.org/10.1056/NEJMoa1300662

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, Bessette B, Boulassel MR, Delwart E, Sepulveda H, Balderas RS, Routy JP, Haddad EK, Sekaly RP (2006) Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med 12(10):1198–1202. https://doi.org/10.1038/nm1482

    CAS  CrossRef  PubMed  Google Scholar 

  • Vallejo A, Gutierrez C, Hernandez-Novoa B, Diaz L, Madrid N, Abad-Fernandez M, Dronda F, Perez-Elias MJ, Zamora J, Munoz E, Munoz-Fernandez MA, Moreno S (2012) The effect of intensification with raltegravir on the HIV-1 reservoir of latently infected memory CD4 T cells in suppressed patients. AIDS 26(15):1885–1894. https://doi.org/10.1097/QAD.0b013e3283584521

    CAS  CrossRef  PubMed  Google Scholar 

  • Van Lint C, Emiliani S, Ott M, Verdin E (1996) Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation. EMBO J 15(5):1112–1120

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • van Praag RM, Prins JM, Roos MT, Schellekens PT, Ten Berge IJ, Yong SL, Schuitemaker H, Eerenberg AJ, Jurriaans S, de WF, Fox CH, Goudsmit J, Miedema F, Lange JM (2001) OKT3 and IL-2 treatment for purging of the latent HIV-1 reservoir in vivo results in selective long-lasting CD4+ T cell depletion. J ClinImmunol 21(3):218–226

    Google Scholar 

  • Velu V, Titanji K, Zhu B, Husain S, Pladevega A, Lai L, Vanderford TH, Chennareddi L, Silvestri G, Freeman GJ, Ahmed R, Amara RR (2009) Enhancing SIV-specific immunity in vivo by PD-1 blockade. Nature 458(7235):206–210. https://doi.org/10.1038/nature07662

    CAS  CrossRef  PubMed  Google Scholar 

  • Verdin E, Paras P, Jr., Van Lint C (1993) Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation. EMBO J 12 (8):3249-3259

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Vibholm L (2017) Short-course TLR9 agonist treatment impacts innate immunity and plasma Viremia in individuals with HIV infection. Clin Infect Dis in press

    Google Scholar 

  • Volberding PA, Deeks SG (2010) Antiretroviral therapy and management of HIV infection. Lancet 376(9734):49–62. https://doi.org/10.1016/S0140-6736(10)60676-9

    CrossRef  PubMed  Google Scholar 

  • Wang CX, Cannon PM (2016) The clinical applications of genome editing in HIV. Blood 127(21):2546–2552. https://doi.org/10.1182/blood-2016-01-678144

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • 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 (2005) 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 115(1):128–137

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, Hoeller C, Khushalani NI, Miller WH, Jr., Lao CD, Linette GP, Thomas L, Lorigan P, Grossmann KF, Hassel JC, Maio M, Sznol M, Ascierto PA, Mohr P, Chmielowski B, Bryce A, Svane IM, Grob JJ, Krackhardt AM, Horak C, Lambert A, Yang AS, Larkin J (2015) Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 16 (4):375-384. doi:https://doi.org/10.1016/S1470-2045(15)70076-8

    CAS  CrossRef  PubMed  Google Scholar 

  • 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 (2014) 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 10(4):e1004071. https://doi.org/10.1371/journal.ppat.1004071

    CrossRef  PubMed  PubMed Central  Google Scholar 

  • Whitney JB, Hill AL, Sanisetty S, Penaloza-MacMaster P, Liu J, Shetty M, Parenteau L, Cabral C, Shields J, Blackmore S, Smith JY, Brinkman AL, Peter LE, Mathew SI, Smith KM, Borducchi EN, Rosenbloom DI, Lewis MG, Hattersley J, Li B, Hesselgesser J, Geleziunas R, Robb ML, Kim JH, Michael NL, Barouch DH (2014) Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature. https://doi.org/10.1038/nature13594

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Whitney JB, Lim SY, Osuna C, Sanisetty S, Barnes TL, Cihlar T, Miller M, Geleziunas R, Hesselgesser J (2016) Repeated TLR7 agonist treatment of SIV+ monkeys on ART can lead to viral remission. Paper presented at the conference on retroviruses and opportunistic infections, Boston, MA

    Google Scholar 

  • Wightman F, Ellenberg P, Churchill M, Lewin SR (2012) HDAC inhibitors in HIV. Immunol Cell Biol 90(1):47–54. https://doi.org/10.1038/icb.2011.95

    CAS  CrossRef  PubMed  Google Scholar 

  • Wightman F, Solomon A, Kumar SS, Urriola N, Gallagher K, Hiener B, Palmer S, McNeil C, Garsia R, Lewin SR (2015) Effect of ipilimumab on the HIV reservoir in an HIV-infected individual with metastatic melanoma. AIDS 29(4):504–506. https://doi.org/10.1097/QAD.0000000000000562

    CrossRef  PubMed  Google Scholar 

  • Yang HC, Xing S, Shan L, O'Connell K, Dinoso J, Shen A, Zhou Y, Shrum CK, Han Y, Liu JO, Zhang H, Margolick JB, Siliciano RF (2009) Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation. J Clin Invest 119(11):3473–3486. https://doi.org/10.1172/JCI39199

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  • Ylisastigui L, Archin NM, Lehrman G, Bosch RJ, Margolis DM (2004) Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression. AIDS 18(8):1101–1108

    CAS  CrossRef  PubMed  Google Scholar 

  • Yukl SA, Boritz E, Busch M, Bentsen C, Chun TW, Douek D, Eisele E, Haase A, Ho YC, Hutter G, Justement JS, Keating S, Lee TH, Li P, Murray D, Palmer S, Pilcher C, Pillai S, Price RW, Rothenberger M, Schacker T, Siliciano J, Siliciano R, Sinclair E, Strain M, Wong J, Richman D, Deeks SG (2013) Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patient. PLoS Pathog 9(5):e1003347. https://doi.org/10.1371/journal.ppat.1003347

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

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Rasmussen, T.A., Søgaard, O.S. (2018). Clinical Interventions in HIV Cure Research. In: Zhang, L., Lewin, S. (eds) HIV Vaccines and Cure . Advances in Experimental Medicine and Biology, vol 1075. Springer, Singapore. https://doi.org/10.1007/978-981-13-0484-2_12

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