{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:23:28Z","timestamp":1777433008524,"version":"3.51.4"},"reference-count":125,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["AIDS Research and Human Retroviruses"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:p>The persistence of HIV in the spleen, despite combination antiretroviral therapy, is not well understood. Sustained immune dysregulation and delayed immune recovery, in addition to immune cell exhaustion, may contribute to persistence of infection in the spleen. Eliminating HIV from this secondary lymphoid organ will require a thorough understanding of antiretroviral (ARV) pharmacology in the spleen, which has been minimally investigated. Low ARV exposure within the spleen may hinder the achievement of a functional or sterilizing cure if cells are not protected from HIV infection. In this study, we provide an overview of the anatomy and physiology of the spleen, review the evidence of the spleen as a site for persistence of HIV, discuss the consequences of persistence of HIV in the spleen, address challenges to eradicating HIV in the spleen, and examine opportunities for future curative efforts.<\/jats:p>","DOI":"10.1089\/aid.2020.0266","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T02:58:36Z","timestamp":1611716316000},"page":"725-735","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Human Immunodeficiency Virus Persistence in the Spleen: Opportunities for Pharmacologic Intervention"],"prefix":"10.1177","volume":"37","author":[{"given":"Aaron S.","family":"Devanathan","sequence":"first","affiliation":[{"name":"UNC Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela D.M.","family":"Kashuba","sequence":"additional","affiliation":[{"name":"UNC Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA."},{"name":"Division of Infectious Diseases, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32833a3946"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5341.1291"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328340a239"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000293"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/387188a0"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm880"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4113"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17057-y"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00895"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh292"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0b013e32835fc68a"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318249111"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4411"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2016.0253"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1669"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/01926230600867743"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12469"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18061249"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1259\/0007-1285-59-699-209"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018943613122"},{"key":"e_1_3_4_22_2","first-page":"613","article-title":"Comparative aspects of splenic microcirculatory pathways in mammals: The region bordering the white pulp","volume":"7","author":"Schmidt EE","year":"1993","unstructured":"Schmidt EE, , MacDonald IC, , Groom AC: Comparative aspects of splenic microcirculatory pathways in mammals: The region bordering the white pulp. Scanning Microsc, 1993; 7:613\u2013628.","journal-title":"Scanning Microsc"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1309\/UXLE9RHL968TER7B"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2010.01.004"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/hon.820"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2012-0251"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11904-014-0207-y"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1086\/514113"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-017-0387-9"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.20411\/pai.v1i1.100"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2017.0254"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aav2045"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005287"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003853"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3109"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004096"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1086\/510852"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11904-009-0005-0"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1086\/500368"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02761999000600019"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.3.1154"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0216413"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.13.5.556-560.2006"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1086\/590112"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002437"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3181e66216"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001427"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy064"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2013.3728"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1086\/374786"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1086\/605890"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1086\/652749"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.001"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000842"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir214"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.010"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175202"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0344-0338(88)80089-X"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/0923-2516(90)90018-E"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.03.019"},{"key":"e_1_3_4_61_2","first-page":"570","article-title":"HIV latency","volume":"345","author":"Wagner TA","year":"2014","unstructured":"Wagner TA, , McLaughlin S, , Garg K, et al.: HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection. Science, 2014; 345:570\u2013573.","journal-title":"Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection. Science"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2055-6640(20)30490-8"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1522675113"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02139-15"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01270-19"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv092"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00419-09"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.5.1898-1906.2005"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01384-20"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01639-19"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.05.033"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16933"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.10.001"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2000.01816.x"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2257.1987.tb00091.x"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2257.1991.tb00250.x"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705940"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200102000-00030"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3182986ff8"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm476"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04952-14"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aap8758"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-014-8220-y"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.1039\/C6AN01189F"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13361-012-0505-9"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1038\/487439a"},{"key":"e_1_3_4_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.04.004"},{"key":"e_1_3_4_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0388-4"},{"key":"e_1_3_4_89_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00188-19"},{"key":"e_1_3_4_90_2","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918788648"},{"key":"e_1_3_4_91_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00942-08"},{"key":"e_1_3_4_92_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1711460"},{"key":"e_1_3_4_93_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000473"},{"key":"e_1_3_4_94_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02323"},{"key":"e_1_3_4_95_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1808729"},{"key":"e_1_3_4_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2012.08.001"},{"key":"e_1_3_4_97_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.170"},{"key":"e_1_3_4_98_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-011-9232-2"},{"key":"e_1_3_4_99_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-014-9374-0"},{"key":"e_1_3_4_100_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019788"},{"key":"e_1_3_4_101_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9157-5"},{"key":"e_1_3_4_102_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.7.4580"},{"key":"e_1_3_4_103_2","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.28254"},{"key":"e_1_3_4_104_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-018-0455-9"},{"key":"e_1_3_4_105_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000485"},{"key":"e_1_3_4_106_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.66.1.235-243.1992"},{"key":"e_1_3_4_107_2","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2016-0121"},{"key":"e_1_3_4_108_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121977"},{"key":"e_1_3_4_109_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12484"},{"key":"e_1_3_4_110_2","first-page":"2358","article-title":"Mechanisms of adoptive immunotherapy: Improved methods for in vivo tracking of tumor-infiltrating lymphocytes and lymphokine-activated killer cells","volume":"53","author":"Wallace PK","year":"1993","unstructured":"Wallace PK, , Palmer LD, , Perry-Lalley D, et al.: Mechanisms of adoptive immunotherapy: Improved methods for in vivo tracking of tumor-infiltrating lymphocytes and lymphokine-activated killer cells. Cancer Res, 1993; 53:2358\u20132367.","journal-title":"Cancer Res"},{"key":"e_1_3_4_111_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.neo.7900209"},{"key":"e_1_3_4_112_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(97)01036-0"},{"key":"e_1_3_4_113_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.118.252858"},{"key":"e_1_3_4_114_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V38.3.360.360"},{"key":"e_1_3_4_115_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880538"},{"key":"e_1_3_4_116_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07472"},{"key":"e_1_3_4_117_2","doi-asserted-by":"publisher","DOI":"10.1111\/1348-0421.12228"},{"key":"e_1_3_4_118_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2705"},{"key":"e_1_3_4_119_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141642"},{"key":"e_1_3_4_120_2","doi-asserted-by":"publisher","DOI":"10.1038\/35051594"},{"key":"e_1_3_4_121_2","doi-asserted-by":"publisher","DOI":"10.1159\/000335216"},{"key":"e_1_3_4_122_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.10.4595"},{"key":"e_1_3_4_123_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.66.5.705"},{"key":"e_1_3_4_124_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.15.8207-8215.2003"},{"key":"e_1_3_4_125_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90514-6"},{"key":"e_1_3_4_126_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2622"}],"container-title":["AIDS Research and Human Retroviruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/aid.2020.0266","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/aid.2020.0266","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/aid.2020.0266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:15:40Z","timestamp":1777367740000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.1089\/aid.2020.0266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":125,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1089\/aid.2020.0266"],"URL":"https:\/\/doi.org\/10.1089\/aid.2020.0266","relation":{},"ISSN":["0889-2229","1931-8405"],"issn-type":[{"value":"0889-2229","type":"print"},{"value":"1931-8405","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10]]}}}