{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:15:17Z","timestamp":1791443717632,"version":"4.3.3"},"reference-count":114,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012319","name":"National Center for Global Health and Medicine, Japan","doi-asserted-by":"publisher","award":["22A2005"],"award-info":[{"award-number":["22A2005"]}],"id":[{"id":"10.13039\/100012319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012319","name":"National Center for Global Health and Medicine, Japan","doi-asserted-by":"publisher","award":["20K17480"],"award-info":[{"award-number":["20K17480"]}],"id":[{"id":"10.13039\/100012319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012319","name":"National Center for Global Health and Medicine, Japan","doi-asserted-by":"publisher","award":["23K15385"],"award-info":[{"award-number":["23K15385"]}],"id":[{"id":"10.13039\/100012319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012319","name":"National Center for Global Health and Medicine, Japan","doi-asserted-by":"publisher","award":["23K07944"],"award-info":[{"award-number":["23K07944"]}],"id":[{"id":"10.13039\/100012319","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS KAKENHI","award":["22A2005"],"award-info":[{"award-number":["22A2005"]}]},{"name":"JSPS KAKENHI","award":["20K17480"],"award-info":[{"award-number":["20K17480"]}]},{"name":"JSPS KAKENHI","award":["23K15385"],"award-info":[{"award-number":["23K15385"]}]},{"name":"JSPS KAKENHI","award":["23K07944"],"award-info":[{"award-number":["23K07944"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Combination antiretroviral therapy (cART) has significantly improved the prognosis of individuals living with human immunodeficiency virus (HIV). Acquired immunodeficiency syndrome has transformed from a fatal disease to a treatable chronic infection. Currently, effective and safe anti-HIV drugs are available. Although cART can reduce viral production in the body of the patient to below the detection limit, it cannot eliminate the HIV provirus integrated into the host cell genome; hence, the virus will be produced again after cART discontinuation. Therefore, research into a cure (or remission) for HIV has been widely conducted. In this review, we focus on drug development targeting cells latently infected with HIV and assess the progress including our current studies, particularly in terms of the \u201cShock and Kill\u201d, and \u201cBlock and Lock\u201d strategies.<\/jats:p>","DOI":"10.3390\/ijms25052621","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T10:47:30Z","timestamp":1708685250000},"page":"2621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["HIV Reservoirs and Treatment Strategies toward Curing HIV Infection"],"prefix":"10.3390","volume":"25","author":[{"given":"Kouki","family":"Matsuda","sequence":"first","affiliation":[{"name":"Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima 890-8544, Japan"},{"name":"AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo 162-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Maeda","sequence":"additional","affiliation":[{"name":"Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima 890-8544, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","unstructured":"UNAIDS (2023, November 10). 2023 Global AIDS Update. Available online: http:\/\/www.unaids.org\/en."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1126\/science.277.5322.112","article-title":"Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease","volume":"277","author":"Autran","year":"1997","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/nm0898-953","article-title":"Restoration of cytomegalovirus-specific CD4+ T-lymphocyte responses after ganciclovir and highly active antiretroviral therapy in individuals infected with HIV-1","volume":"4","author":"Komanduri","year":"1998","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1086\/515591","article-title":"Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: Results of AIDS Clinical Trials Group Protocol 315","volume":"178","author":"Lederman","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1001\/jama.300.1.51","article-title":"Changes in the risk of death after HIV seroconversion compared with mortality in the general population","volume":"300","author":"Bhaskaran","year":"2008","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1086\/505147","article-title":"The survival benefits of AIDS treatment in the United States","volume":"194","author":"Walensky","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/44755","article-title":"Re-emergence of HIV after stopping therapy","volume":"401","author":"Chun","year":"1999","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nrmicro.2015.5","article-title":"HIV reservoirs: What, where and how to target them","volume":"14","author":"Churchill","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1126\/science.278.5341.1295","article-title":"Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy","volume":"278","author":"Finzi","year":"1997","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nm880","article-title":"Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells","volume":"9","author":"Siliciano","year":"2003","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1146\/annurev.med.59.062806.123001","article-title":"Hide-and-seek: The challenge of viral persistence in HIV-1 infection","volume":"59","author":"Geeraert","year":"2008","journal-title":"Annu. Rev. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1038\/s41591-020-1022-1","article-title":"Recommendations for measuring HIV reservoir size in cure-directed clinical trials","volume":"26","author":"Richman","year":"2020","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1093\/cid\/ciab541","article-title":"Time to Viral Rebound After Interruption of Modern Antiretroviral Therapies","volume":"74","author":"Li","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/nm.1972","article-title":"HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation","volume":"15","author":"Chomont","year":"2009","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1128\/JVI.78.3.1160-1168.2004","article-title":"T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: Implications for HIV pathogenesis","volume":"78","author":"Brenchley","year":"2004","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nm.3445","article-title":"HIV-1 persistence in CD4+ T cells with stem cell-like properties","volume":"20","author":"Buzon","year":"2014","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nature21710","article-title":"CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses","volume":"543","author":"Descours","year":"2017","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1086\/428777","article-title":"Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1","volume":"191","author":"Strain","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1073\/pnas.95.3.1154","article-title":"Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection","volume":"95","author":"Zhang","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.imlet.2006.10.009","article-title":"Lymphocyte numbers and subsets in the human blood. Do they mirror the situation in all organs?","volume":"108","author":"Blum","year":"2007","journal-title":"Immunol. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1146\/annurev.immunol.17.1.625","article-title":"Population biology of HIV-1 infection: Viral and CD4+ T cell demographics and dynamics in lymphatic tissues","volume":"17","author":"Haase","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nm.4113","article-title":"PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals","volume":"22","author":"Banga","year":"2016","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eaaz0802","DOI":"10.1126\/scitranslmed.aaz0802","article-title":"Single-cell transcriptional landscapes reveal HIV-1-driven aberrant host gene transcription as a potential therapeutic target","volume":"12","author":"Liu","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1172\/JCI124291","article-title":"Intact HIV-1 proviruses accumulate at distinct chromosomal positions during prolonged antiretroviral therapy","volume":"129","author":"Einkauf","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.cell.2015.01.020","article-title":"HIV-1 integration landscape during latent and active infection","volume":"160","author":"Cohn","year":"2015","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.cell.2013.09.020","article-title":"Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure","volume":"155","author":"Ho","year":"2013","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Telwatte, S., Lee, S., Somsouk, M., Hatano, H., Baker, C., Kaiser, P., Kim, P., Chen, T.H., Milush, J., and Hunt, P.W. (2018). Gut and blood differ in constitutive blocks to HIV transcription, suggesting tissue-specific differences in the mechanisms that govern HIV latency. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007357"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.cell.2021.12.011","article-title":"Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses","volume":"185","author":"Einkauf","year":"2022","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41586-020-2651-8","article-title":"Distinct viral reservoirs in individuals with spontaneous control of HIV-1","volume":"585","author":"Jiang","year":"2020","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1172\/JCI80567","article-title":"Measuring the latent reservoir in vivo","volume":"126","author":"Massanella","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Eriksson, S., Graf, E.H., Dahl, V., Strain, M.C., Yukl, S.A., Lysenko, E.S., Bosch, R.J., Lai, J., Chioma, S., and Emad, F. (2013). Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003174"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/978-1-62703-670-2_21","article-title":"Quantification of total HIV1-DNA in peripheral blood mononuclear cells","volume":"1087","author":"Rouzioux","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12385","DOI":"10.1128\/JVI.00609-14","article-title":"Cross-clade ultrasensitive PCR-based assays to measure HIV persistence in large-cohort studies","volume":"88","author":"Vandergeeten","year":"2014","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41586-019-0898-8","article-title":"A quantitative approach for measuring the reservoir of latent HIV-1 proviruses","volume":"566","author":"Bruner","year":"2019","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100122","DOI":"10.1016\/j.crmeth.2021.100122","article-title":"A widely distributed HIV-1 provirus elimination assay to evaluate latency-reversing agents in vitro","volume":"1","author":"Matsuda","year":"2021","journal-title":"Cell Rep. Methods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E3659","DOI":"10.1073\/pnas.1617961114","article-title":"Single-cell analysis of HIV-1 transcriptional activity reveals expression of proviruses in expanded clones during ART","volume":"114","author":"Wiegand","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Anderson, E.M., Simonetti, F.R., Gorelick, R.J., Hill, S., Gouzoulis, M.A., Bell, J., Rehm, C., Perez, L., Boritz, E., and Wu, X. (2020). Dynamic Shifts in the HIV Proviral Landscape During Long Term Combination Antiretroviral Therapy: Implications for Persistence and Control of HIV Infections. Viruses, 12.","DOI":"10.3390\/v12020136"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13193","DOI":"10.1073\/pnas.94.24.13193","article-title":"Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy","volume":"94","author":"Chun","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1097\/QAD.0b013e3282fd6df4","article-title":"Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells","volume":"22","author":"Archin","year":"2008","journal-title":"AIDS"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1093\/infdis\/164.4.828","article-title":"Can in vivo surveys on the chemosensitivity of Plasmodium falciparum still be done in tropical Africa?","volume":"164","author":"Carme","year":"1991","journal-title":"J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1126\/science.278.5341.1291","article-title":"Recovery of replication-competent HIV despite prolonged suppression of plasma viremia","volume":"278","author":"Wong","year":"1997","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2174\/1570162043484915","article-title":"Can HIV be Cured? Mechanisms of HIV persistence and strategies to combat it","volume":"2","author":"Hamer","year":"2004","journal-title":"Curr. HIV Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1016\/S0140-6736(13)60104-X","article-title":"Barriers to a cure for HIV: New ways to target and eradicate HIV-1 reservoirs","volume":"381","author":"Katlama","year":"2013","journal-title":"Lancet"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1126\/science.1165706","article-title":"The challenge of finding a cure for HIV infection","volume":"323","author":"Richman","year":"2009","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1146\/annurev-virology-091919-103029","article-title":"The Current Status of Latency Reversing Agents for HIV-1 Remission","volume":"8","author":"Rodari","year":"2021","journal-title":"Annu. Rev. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/jmp.12613","article-title":"The role of latency reversal in HIV cure strategies","volume":"51","author":"Tanaka","year":"2022","journal-title":"J. Med. Primatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.chom.2017.12.004","article-title":"Getting the \u201cKill\u201d into \"Shock and Kill\": Strategies to Eliminate Latent HIV","volume":"23","author":"Kim","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1074\/jbc.RA118.005798","article-title":"Benzolactam-related compounds promote apoptosis of HIV-infected human cells via protein kinase C-induced HIV latency reversal","volume":"294","author":"Matsuda","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Matsuda, K., Kobayakawa, T., Kariya, R., Tsuchiya, K., Ryu, S., Tsuji, K., Ishii, T., Gatanaga, H., Yoshimura, K., and Okada, S. (2021). A Therapeutic Strategy to Combat HIV-1 Latently Infected Cells with a Combination of Latency-Reversing Agents Containing DAG-Lactone PKC Activators. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.636276"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nature11286","article-title":"Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy","volume":"487","author":"Archin","year":"2012","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1016\/S2352-3018(14)70014-1","article-title":"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","volume":"1","author":"Rasmussen","year":"2014","journal-title":"Lancet HIV"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1097\/QAD.0000000000001064","article-title":"Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy","volume":"30","author":"Gutierrez","year":"2016","journal-title":"AIDS"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e520","DOI":"10.1016\/S2352-3018(15)00226-X","article-title":"Short-term administration of disulfiram for reversal of latent HIV infection: A phase 2 dose-escalation study","volume":"2","author":"Elliott","year":"2015","journal-title":"Lancet HIV"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sogaard, O.S., Graversen, M.E., Leth, S., Olesen, R., Brinkmann, C.R., Nissen, S.K., Kjaer, A.S., Schleimann, M.H., Denton, P.W., and Hey-Cunningham, W.J. (2015). The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005142"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/S0140-6736(19)32990-3","article-title":"Antiretroviral therapy alone versus antiretroviral therapy with a kick and kill approach, on measures of the HIV reservoir in participants with recent HIV infection (the RIVER trial): A phase 2, randomised trial","volume":"395","author":"Fidler","year":"2020","journal-title":"Lancet"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.virol.2014.02.008","article-title":"Transcriptional control of HIV latency: Cellular signaling pathways, epigenetics, happenstance and the hope for a cure","volume":"454\u2013455","author":"Mbonye","year":"2014","journal-title":"Virology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.chom.2020.03.014","article-title":"The Biology of the HIV-1 Latent Reservoir and Implications for Cure Strategies","volume":"27","author":"Cohn","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nm.3489","article-title":"New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo","volume":"20","author":"Bullen","year":"2014","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.immuni.2018.04.030","article-title":"Targeting the Latent Reservoir for HIV-1","volume":"48","author":"Sengupta","year":"2018","journal-title":"Immunity"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7078","DOI":"10.1073\/pnas.1402873111","article-title":"Quantification of HIV-1 latency reversal in resting CD4+ T cells from patients on suppressive antiretroviral therapy","volume":"111","author":"Cillo","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"10803","DOI":"10.1128\/JVI.00320-14","article-title":"The histone deacetylase inhibitor vorinostat (SAHA) increases the susceptibility of uninfected CD4+ T cells to HIV by increasing the kinetics and efficiency of postentry viral events","volume":"88","author":"Lucera","year":"2014","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1021\/jm990613q","article-title":"Conformationally constrained analogues of diacylglycerol (DAG). 17. Contrast between sn-1 and sn-2 DAG lactones in binding to protein kinase C","volume":"43","author":"Tamamura","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"28495","DOI":"10.1074\/jbc.270.48.28495","article-title":"Protein kinase C: Structure, function, and regulation","volume":"270","author":"Newton","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s11904-007-0009-6","article-title":"Confronting proviral HIV infection","volume":"4","author":"Margolis","year":"2007","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1172\/JCI80142","article-title":"Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations","volume":"125","author":"Laird","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Jiang, G., Mendes, E.A., Kaiser, P., Wong, D.P., Tang, Y., Cai, I., Fenton, A., Melcher, G.P., Hildreth, J.E., and Thompson, G.R. (2015). Synergistic Reactivation of Latent HIV Expression by Ingenol-3-Angelate, PEP005, Targeted NF-kB Signaling in Combination with JQ1 Induced p-TEFb Activation. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005066"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"115449","DOI":"10.1016\/j.ejmech.2023.115449","article-title":"Synthesis and evaluation of DAG-lactone derivatives with HIV-1 latency reversing activity","volume":"256","author":"Ishii","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Hattori, S.I., Matsuda, K., Tsuchiya, K., Gatanaga, H., Oka, S., Yoshimura, K., Mitsuya, H., and Maeda, K. (2018). Combination of a Latency-Reversing Agent with a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02022"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0092-8674(02)00864-4","article-title":"HIV-1 integration in the human genome favors active genes and local hotspots","volume":"110","author":"Schroder","year":"2002","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e34655","DOI":"10.7554\/eLife.34655","article-title":"Distinct chromatin functional states correlate with HIV latency reactivation in infected primary CD4(+) T cells","volume":"7","author":"Battivelli","year":"2018","journal-title":"eLife"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1126\/science.1254194","article-title":"HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells","volume":"345","author":"Maldarelli","year":"2014","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1126\/science.1256304","article-title":"HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection","volume":"345","author":"Wagner","year":"2014","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nm.4156","article-title":"Defective proviruses rapidly accumulate during acute HIV-1 infection","volume":"22","author":"Bruner","year":"2016","journal-title":"Nat. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S1074-7613(03)00236-X","article-title":"Molecular characterization, reactivation, and depletion of latent HIV","volume":"19","author":"Brooks","year":"2003","journal-title":"Immunity"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/s41586-020-1946-0","article-title":"Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8(+) cells","volume":"578","author":"McBrien","year":"2020","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41586-020-1951-3","article-title":"Systemic HIV and SIV latency reversal via non-canonical NF-kappaB signalling in vivo","volume":"578","author":"Nixon","year":"2020","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e00337-19","DOI":"10.1128\/mBio.00337-19","article-title":"Entry of Polarized Effector Cells into Quiescence Forces HIV Latency","volume":"10","author":"Dobrowolski","year":"2019","journal-title":"mBio"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1182\/blood-2008-07-168393","article-title":"Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells","volume":"113","author":"Bosque","year":"2009","journal-title":"Blood"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1172\/JCI97555","article-title":"Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells","volume":"128","author":"Huang","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Lassen, K.G., Hebbeler, A.M., Bhattacharyya, D., Lobritz, M.A., and Greene, W.C. (2012). A flexible model of HIV-1 latency permitting evaluation of many primary CD4 T-cell reservoirs. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030176"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4161","DOI":"10.1182\/blood-2007-06-097907","article-title":"CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T cells to HIV-1 infection: A novel model of HIV-1 latency","volume":"110","author":"Saleh","year":"2007","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.immuni.2012.01.014","article-title":"Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation","volume":"36","author":"Shan","year":"2012","journal-title":"Immunity"},{"key":"ref_83","first-page":"3473","article-title":"Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation","volume":"119","author":"Yang","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.chom.2012.05.016","article-title":"An analog of the natural steroidal alkaloid cortistatin A potently suppresses Tat-dependent HIV transcription","volume":"12","author":"Mousseau","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/BF00125123","article-title":"A region of basic amino-acid cluster in HIV-1 Tat protein is essential for trans-acting activity and nucleolar localization","volume":"3","author":"Endo","year":"1989","journal-title":"Virus Genes"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.celrep.2017.09.080","article-title":"In Vivo Suppression of HIV Rebound by Didehydro-Cortistatin A, a \"Block-and-Lock\" Strategy for HIV-1 Treatment","volume":"21","author":"Kessing","year":"2017","journal-title":"Cell Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"64","DOI":"10.2174\/1570162X13666150121111548","article-title":"Didehydro-cortistatin A inhibits HIV-1 Tat mediated neuroinflammation and prevents potentiation of cocaine reward in Tat transgenic mice","volume":"13","author":"Mediouni","year":"2015","journal-title":"Curr. HIV Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"95ra74","DOI":"10.1126\/scitranslmed.3002530","article-title":"Curaxins: Anticancer compounds that simultaneously suppress NF-kappaB and activate p53 by targeting FACT","volume":"3","author":"Gasparian","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12977-020-00547-9","article-title":"Modulation of BRD4 in HIV epigenetic regulation: Implications for finding an HIV cure","volume":"18","author":"Alamer","year":"2021","journal-title":"Retrovirology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1172\/JCI120633","article-title":"Structure-guided drug design identifies a BRD4-selective small molecule that suppresses HIV","volume":"129","author":"Niu","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Vansant, G., Bruggemans, A., Janssens, J., and Debyser, Z. (2020). Block-And-Lock Strategies to Cure HIV Infection. Viruses, 12.","DOI":"10.3390\/v12010084"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"18581","DOI":"10.1073\/pnas.1003059107","article-title":"IL-33 is a crucial amplifier of innate rather than acquired immunity","volume":"107","author":"Oboki","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"24581","DOI":"10.1074\/jbc.M111.248021","article-title":"Impaired infectivity of ritonavir-resistant HIV is rescued by heat shock protein 90AB1","volume":"286","author":"Joshi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"28896","DOI":"10.1038\/srep28896","article-title":"Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-dependent manner","volume":"6","author":"Kim","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"10332","DOI":"10.1074\/jbc.M116.717538","article-title":"Inhibition of Heat Shock Protein 90 Prevents HIV Rebound","volume":"291","author":"Joshi","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Gavegnano, C., Brehm, J.H., Dupuy, F.P., Talla, A., Ribeiro, S.P., Kulpa, D.A., Cameron, C., Santos, S., Hurwitz, S.J., and Marconi, V.C. (2017). Novel mechanisms to inhibit HIV reservoir seeding using Jak inhibitors. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006740"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1128\/AAC.02496-13","article-title":"Ruxolitinib and tofacitinib are potent and selective inhibitors of HIV-1 replication and virus reactivation in vitro","volume":"58","author":"Gavegnano","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/cid\/ciab212","article-title":"Randomized Trial of Ruxolitinib in Antiretroviral-Treated Adults with Human Immunodeficiency Virus","volume":"74","author":"Marconi","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.chom.2016.11.001","article-title":"The mTOR Complex Controls HIV Latency","volume":"20","author":"Besnard","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41426-018-0139-5","article-title":"TSC1 and DEPDC5 regulate HIV-1 latency through the mTOR signaling pathway","volume":"7","author":"Jin","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/COH.0000000000000600","article-title":"Broadly neutralizing antibodies for the treatment and prevention of HIV infection","volume":"15","author":"Caskey","year":"2020","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1146\/annurev-immunol-051116-052433","article-title":"Signaling by Antibodies: Recent Progress","volume":"35","author":"Bournazos","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1126\/science.aaf1279","article-title":"Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo","volume":"352","author":"Lu","year":"2016","journal-title":"Science"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.cell.2017.06.048","article-title":"Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo","volume":"170","author":"Horwitz","year":"2017","journal-title":"Cell"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nature21435","article-title":"Early antibody therapy can induce long-lasting immunity to SHIV","volume":"543","author":"Nishimura","year":"2017","journal-title":"Nature"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/s41586-018-0600-6","article-title":"Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys","volume":"563","author":"Borducchi","year":"2018","journal-title":"Nature"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"319ra206","DOI":"10.1126\/scitranslmed.aad5752","article-title":"Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection","volume":"7","author":"Lynch","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1084\/jem.20180936","article-title":"Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117","volume":"215","author":"Cohen","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41586-018-0531-2","article-title":"Combination therapy with anti-HIV-1 antibodies maintains viral suppression","volume":"561","author":"Mendoza","year":"2018","journal-title":"Nature"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41586-022-04597-1","article-title":"Prolonged viral suppression with anti-HIV-1 antibody therapy","volume":"606","author":"Gaebler","year":"2022","journal-title":"Nature"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e150211","DOI":"10.1172\/JCI150211","article-title":"Broadly neutralizing antibody-derived CAR T cells reduce viral reservoir in individuals infected with HIV-1","volume":"131","author":"Liu","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/j.immuni.2023.04.019","article-title":"Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques","volume":"56","author":"Wu","year":"2023","journal-title":"Immunity"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/cid\/ciu766","article-title":"Progress toward curing HIV infections with hematopoietic stem cell transplantation","volume":"60","author":"Smiley","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12981-022-00483-y","article-title":"CRISPR\/Cas9: A tool to eradicate HIV-1","volume":"19","author":"Bhowmik","year":"2022","journal-title":"AIDS Res. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/5\/2621\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:03:58Z","timestamp":1760105038000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/5\/2621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,23]]},"references-count":114,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25052621"],"URL":"https:\/\/doi.org\/10.3390\/ijms25052621","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,23]]}}}