{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:34:17Z","timestamp":1778873657084,"version":"3.51.4"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Replication-competent human immunodeficiency virus (HIV) persists in infected people despite suppressive combination antiretroviral therapy (cART), and it represents a major obstacle to HIV functional cure or eradication. We have developed a model of cART-mediated viral suppression in simian human immunodeficiency virus (SIV) mac239-infected Indian rhesus macaques and evaluated the impact of the histone deacetylase inhibitor (HDACi) romidepsin (RMD) on viremia\n            <jats:italic>in vivo<\/jats:italic>\n            . Eight macaques virologically suppressed to clinically relevant levels (&lt;30 viral RNA copies\/ml of plasma), using a three-class five-drug cART regimen, received multiple intravenous infusions of either RMD (\n            <jats:italic>n<\/jats:italic>\n            = 5) or saline (\n            <jats:italic>n<\/jats:italic>\n            = 3) starting 31 to 54 weeks after cART initiation.\n            <jats:italic>In vivo<\/jats:italic>\n            RMD treatment resulted in significant transient increases in acetylated histone levels in CD4\n            <jats:sup>+<\/jats:sup>\n            T cells. RMD-treated animals demonstrated plasma viral load measurements for each 2-week treatment cycle that were significantly higher than those in saline control-treated animals during periods of treatment, suggestive of RMD-induced viral reactivation. However, plasma virus rebound was indistinguishable between RMD-treated and control-treated animals for a subset of animals released from cART. These findings suggest that HDACi drugs, such as RMD, can reactivate residual virus in the presence of suppressive antiviral therapy and may be a valuable component of a comprehensive HIV functional cure\/eradication strategy.\n          <\/jats:p>","DOI":"10.1128\/aac.02625-15","type":"journal-article","created":{"date-parts":[[2015,12,29]],"date-time":"2015-12-29T03:23:15Z","timestamp":1451359395000},"page":"1560-1572","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Elevated Plasma Viral Loads in Romidepsin-Treated Simian Immunodeficiency Virus-Infected Rhesus Macaques on Suppressive Combination Antiretroviral Therapy"],"prefix":"10.1128","volume":"60","author":[{"given":"Gregory Q.","family":"Del Prete","sequence":"first","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelli","family":"Oswald","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail","family":"Lara","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Shoemaker","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Smedley","sequence":"additional","affiliation":[{"name":"Laboratory Animal Sciences Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhonda","family":"Macallister","sequence":"additional","affiliation":[{"name":"Laboratory Animal Sciences Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicky","family":"Coalter","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Wiles","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodney","family":"Wiles","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randy","family":"Fast","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Kiser","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Lu","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim","family":"Zheng","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. Gregory","family":"Alvord","sequence":"additional","affiliation":[{"name":"Statistical Consulting, Data Management Services, Inc., Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles M.","family":"Trubey","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Michael","family":"Piatak","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Deleage","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon F.","family":"Keele","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob D.","family":"Estes","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Hesselgesser","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romas","family":"Geleziunas","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey D.","family":"Lifson","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328340a239"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.15109"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.13193"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1295-1284"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/8394"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1291"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/387183a0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1472-6963-10-S1-S2","article-title":"Financing equitable access to antiretroviral treatment in South Africa","volume":"10","author":"Cleary S","year":"2010","unstructured":"Cleary S, McIntyre D. 2010. Financing equitable access to antiretroviral treatment in South Africa. BMC Health Serv Res 10 (Suppl 1):S2.","journal-title":"BMC Health Serv Res"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11904-012-0118-8"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e318285cd33"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000118"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61113-7"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.300.1.51"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-146-2-200701160-00003"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/644772"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1086\/374786"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200209270-00002"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328337b957"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1086\/652749"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir507"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit311"},{"key":"e_1_3_2_23_2","first-page":"318","article-title":"HIV-1 eradication strategies: design and assessment","volume":"8","author":"Siliciano JD","year":"2013","unstructured":"Siliciano JD, Siliciano RF. 2013. HIV-1 eradication strategies: design and assessment. Curr Opin HIV AIDS 8:318\u2013325.","journal-title":"Curr Opin HIV AIDS"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1165706"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/v5030902"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02413-12"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01519-09"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02585-08"},{"key":"e_1_3_2_29_2","first-page":"371","article-title":"Chromatin-associated regulation of HIV-1 transcription: implications for the development of therapeutic strategies","volume":"41","author":"Quivy V","year":"2007","unstructured":"Quivy V, De Walque S, Van Lint C. 2007. Chromatin-associated regulation of HIV-1 transcription: implications for the development of therapeutic strategies. Subcell Biochem 41:371\u2013396.","journal-title":"Subcell Biochem"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200405210-00003"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1086\/423822"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807898200"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2008.0191"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32832ec1dc"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11286"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004071"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu155"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004473"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005142"},{"key":"e_1_3_2_40_2","first-page":"262","article-title":"Considerations in the development of nonhuman primate models of combination antiretroviral therapy for studies of AIDS virus suppression, residual virus, and curative strategies","volume":"8","author":"Del Prete GQ","year":"2013","unstructured":"Del Prete GQ, Lifson JD. 2013. Considerations in the development of nonhuman primate models of combination antiretroviral therapy for studies of AIDS virus suppression, residual virus, and curative strategies. Curr Opin HIV AIDS 8:262\u2013272.","journal-title":"Curr Opin HIV AIDS"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03746-14"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13594"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06886-11"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis643"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-0318-1"},{"key":"e_1_3_2_46_2","first-page":"27","volume-title":"Analysis of repeated measures","author":"Crowder MJ","year":"1990","unstructured":"Crowder MJ, Hand DJ. 1990. Analysis of repeated measures, p 27\u201342. Chapman and Hall, London, United Kingdom."},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-004-0766-5"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-1215"},{"key":"e_1_3_2_49_2","volume-title":"Istodax (romidepsin) for injection. Highlights of prescribing information","author":"Celgene Corporation","unstructured":"Celgene Corporation. Istodax (romidepsin) for injection. Highlights of prescribing information. Celgene Corporation, Summit, NJ."},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2015.0130"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00350-08"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.23800"},{"key":"e_1_3_2_53_2","first-page":"4916","article-title":"FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases","volume":"62","author":"Furumai R","year":"2002","unstructured":"Furumai R, Matsuyama A, Kobashi N, Lee KH, Nishiyama M, Nakajima H, Tanaka A, Komatsu Y, Nishino N, Yoshida M, Horinouchi S. 2002. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res 62:4916\u20134921.","journal-title":"Cancer Res"},{"key":"e_1_3_2_54_2","first-page":"718","article-title":"Phase I trial of the histone deacetylase inhibitor, depsipeptide (FR901228, NSC 630176), in patients with refractory neoplasms","volume":"8","author":"Sandor V","year":"2002","unstructured":"Sandor V, Bakke S, Robey RW, Kang MH, Blagosklonny MV, Bender J, Brooks R, Piekarz RL, Tucker E, Figg WD, Chan KK, Goldspiel B, Fojo AT, Balcerzak SP, Bates SE. 2002. Phase I trial of the histone deacetylase inhibitor, depsipeptide (FR901228, NSC 630176), in patients with refractory neoplasms. Clin Cancer Res 8:718\u2013728.","journal-title":"Clin Cancer Res"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1802"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.1984"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1406663111"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.01.014"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14053"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00161-10"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80142"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.2174\/157016210793499312"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006093"},{"key":"e_1_3_2_64_2","volume-title":"Guide for the care and use of laboratory animals","author":"National Research Council","year":"2011","unstructured":"National Research Council. 2011. Guide for the care and use of laboratory animals, 8th ed. National Academies Press, Washington, DC.","edition":"8"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02625-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02625-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:37:24Z","timestamp":1645475844000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02625-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3]]},"references-count":63,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1128\/AAC.02625-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.02625-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3]]},"assertion":[{"value":"2015-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}