{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T10:16:30Z","timestamp":1768731390938,"version":"3.49.0"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T00:00:00Z","timestamp":1474848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"University of Missouri Research Board"},{"name":"Start-up fund, University of Missouri\u2014Kansas City"},{"DOI":"10.13039\/100000015","name":"U.S. Department of Energy","doi-asserted-by":"crossref","award":["DE-AC52-06NA25396"],"award-info":[{"award-number":["DE-AC52-06NA25396"]}],"id":[{"id":"10.13039\/100000015","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AI028433"],"award-info":[{"award-number":["R01-AI028433"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Center for Research Resources and the Office of Research Infrastructure Programs (ORIP)","award":["R01-OD011095"],"award-info":[{"award-number":["R01-OD011095"]}]},{"name":"NIDA","award":["DA015013"],"award-info":[{"award-number":["DA015013"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AI104373"],"award-info":[{"award-number":["R01-AI104373"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1005127","type":"journal-article","created":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T17:34:23Z","timestamp":1474911263000},"page":"e1005127","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Modeling the Effects of Morphine on Simian Immunodeficiency Virus Dynamics"],"prefix":"10.1371","volume":"12","author":[{"given":"Naveen K.","family":"Vaidya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruy M.","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan S.","family":"Perelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2016,9,26]]},"reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/00002030-200001070-00009","article-title":"Overland heroin trafficking routes and HIV-1 spread in south and south-east Asia","volume":"14","author":"C Beyrer","year":"2000","journal-title":"Aids"},{"issue":"1","key":"ref2","first-page":"20","article-title":"Substance abuse and HIV infection","volume":"11","author":"H Francis","year":"2003","journal-title":"Topics in HIV Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"953678","DOI":"10.1155\/2012\/953678","article-title":"Interactive effects of morphine on HIV infection: Role in HIV-associated neurocognitive disorder","volume":"2012","author":"PV Reddy","year":"2012","journal-title":"AIDS Research and Treatment"},{"key":"ref4","unstructured":"CDC. Drug-associated HIV transmission continues in the United States. 2007; April 12, 2013."},{"issue":"18","key":"ref5","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1212\/01.WNL.0000287431.88658.8b","article-title":"Updated research nosology for HIV-associated neurocognitive disorders","volume":"69","author":"A Antinori","year":"2007","journal-title":"Neurology"},{"issue":"3","key":"ref6","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2174\/157016206777709401","article-title":"Impact of HIV on regional & cellular organisation of the brain","volume":"4","author":"JE Bell","year":"2006","journal-title":"Current HIV Res"},{"issue":"Pt 11","key":"ref7","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1093\/brain\/121.11.2043","article-title":"HIV encephalitis, proviral load and dementia in drug users and homosexuals with AIDS. Effect of neocortical involvement","volume":"121","author":"JE Bell","year":"1998","journal-title":"Brain: a journal of neurology"},{"issue":"1","key":"ref8","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1080\/135502801300069737","article-title":"Acceleration of HIV dementia with methamphetamine and cocaine","volume":"7","author":"A Nath","year":"2001","journal-title":"J Neurovirology"},{"issue":"3","key":"ref9","first-page":"241","article-title":"Probable deceleration of progression of Simian AIDS affected by opiate dependency: studies with a rhesus macaque\/SIVsmm9 model","volume":"50","author":"RM Donahoe","year":"2009","journal-title":"JAIDS"},{"issue":"6","key":"ref10","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1093\/clinids\/20.6.1467","article-title":"Injection drug use and human immunodeficiency virus infection","volume":"20","author":"P Alcabes","year":"1995","journal-title":"Clinical Infect Dis"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1016\/S0960-5428(06)80057-4","article-title":"Neuroimmunomodulation by opiates: relationship to HIV-1 infection and AIDS","volume":"3","author":"RM Donahoe","year":"1993","journal-title":"Adv Neuroimmunol"},{"issue":"1\u20132","key":"ref12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0165-5728(97)00224-5","article-title":"Opiates as potential cofactors in progression of HIV-1 infections to AIDS","volume":"83","author":"RM Donahoe","year":"1998","journal-title":"J Neuroimmunol"},{"issue":"7","key":"ref13","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1086\/433175","article-title":"The role of substance abuse in HIV disease progression: reconciling differences from laboratory and epidemiologic investigations","volume":"41","author":"F Kapadia","year":"2005","journal-title":"Clinical Infect Dis: an official publication of the Infectious Diseases Society of America"},{"issue":"24","key":"ref14","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1056\/NEJM199212103272401","article-title":"Clinical manifestations and predictors of disease progression in drug users with human immunodeficiency virus infection","volume":"327","author":"PA Selwyn","year":"1992","journal-title":"N Eng J Med"},{"issue":"1","key":"ref15","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.virol.2006.06.020","article-title":"Chronic morphine exposure causes pronounced virus replication in cerebral compartment and accelerated onset of AIDS in SIV\/SHIV-infected Indian rhesus macaques","volume":"354","author":"R Kumar","year":"2006","journal-title":"Virology"},{"issue":"20","key":"ref16","doi-asserted-by":"crossref","first-page":"11425","DOI":"10.1128\/JVI.78.20.11425-11428.2004","article-title":"Modulation by morphine of viral set point in rhesus macaques infected with simian immunodeficiency virus and simian-human immunodeficiency virus","volume":"78","author":"R Kumar","year":"2004","journal-title":"J Virol"},{"issue":"1","key":"ref17","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s11481-009-9184-0","article-title":"Morphine and rapid disease progression in nonhuman primate model of AIDS: inverse correlation between disease progression and virus evolution","volume":"5","author":"V Rivera-Amill","year":"2010","journal-title":"J Neuroimmune Pharmacology: the official journal of the Society on NeuroImmune Pharmacology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1089\/aid.2010.0012","article-title":"Short communication: Lack of immune response in rapid progressor morphine-dependent and SIV\/SHIV-infected rhesus macaques is correlated with downregulation of TH1 cytokines","volume":"8","author":"V Rivera-Amill","year":"2010","journal-title":"AIDS Res Human Retroviruses"},{"issue":"1","key":"ref19","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1089\/aid.2006.22.114","article-title":"Evolution of SIV envelope in morphine-dependent rhesus macaques with rapid disease progression","volume":"22","author":"G Tirado","year":"2006","journal-title":"AIDS research and human retroviruses"},{"issue":"2","key":"ref20","doi-asserted-by":"crossref","first-page":"e31167","DOI":"10.1371\/journal.pone.0031167","article-title":"Morphine suppresses IFN signaling pathway and enhances AIDS virus infection","volume":"7","author":"Y Wang","year":"2012","journal-title":"PloS One"},{"issue":"13","key":"ref21","doi-asserted-by":"crossref","first-page":"6971","DOI":"10.1073\/pnas.94.13.6971","article-title":"Virus dynamics and drug therapy","volume":"94","author":"S Bonhoeffer","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref22","author":"MA Nowak","year":"2000"},{"issue":"1","key":"ref23","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/nri700","article-title":"Modelling viral and immune system dynamics","volume":"2","author":"AS Perelson","year":"2002","journal-title":"Nature reviews Immunology"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1741-7007-11-96","article-title":"Modeling the within-host dynamics of HIV infection","volume":"11","author":"AS Perelson","year":"2013","journal-title":"BMC biology"},{"issue":"6","key":"ref25","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1136\/jim-50-06-03","article-title":"Morphine enhances HIV infection of human blood mononuclear phagocytes through modulation of beta-chemokines and CCR5 receptor","volume":"50","author":"CJ Guo","year":"2002","journal-title":"J Investig Med"},{"issue":"2","key":"ref26","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1203\/01.PDR.0000074973.83826.4C","article-title":"Morphine enhances HIV infection of neonatal macrophages","volume":"54","author":"Y Li","year":"2003","journal-title":"Pediatr Res"},{"issue":"12","key":"ref27","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1086\/340816","article-title":"Morphine promotes simian acquired immunodeficiency syndrome virus replication in monkey peripheral mononuclear cells: induction of CC chemokine receptor 5 expression for virus entry","volume":"185","author":"S Suzuki","year":"2002","journal-title":"J Infect Dis"},{"issue":"6","key":"ref28","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1084\/jem.190.6.841","article-title":"Viral dynamics of acute HIV-1 infection","volume":"190","author":"SJ Little","year":"1999","journal-title":"The Journal of experimental medicine"},{"issue":"10","key":"ref29","doi-asserted-by":"crossref","first-page":"7518","DOI":"10.1128\/JVI.71.10.7518-7525.1997","article-title":"Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection","volume":"71","author":"MA Nowak","year":"1997","journal-title":"J Virol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1137\/S0036144598335107","article-title":"Mathematical analysis of HIV-1 dynamics of vivo","volume":"41","author":"AS Perelson","year":"1999","journal-title":"SIAM Rev"},{"issue":"5248","key":"ref31","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1126\/science.271.5248.497","article-title":"Reduction of HIV concentration during acute infection: independence from a specific immune response","volume":"271","author":"AN Phillips","year":"1996","journal-title":"Science"},{"issue":"3","key":"ref32","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1006\/jtbi.2000.1076","article-title":"Modeling plasma virus concentration during primary HIV infection","volume":"203","author":"MA Stafford","year":"2000","journal-title":"J Theor Biol"},{"issue":"9","key":"ref33","doi-asserted-by":"crossref","first-page":"4302","DOI":"10.1128\/JVI.02284-09","article-title":"Viral dynamics during primary simian immunodeficiency virus infection: effect of time-dependent virus infectivity","volume":"84","author":"NK Vaidya","year":"2010","journal-title":"J Virol"},{"issue":"5403","key":"ref34","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1126\/science.283.5403.857","article-title":"Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes","volume":"283","author":"JE Schmitz","year":"1999","journal-title":"Science"},{"issue":"4","key":"ref35","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.jtbi.2009.04.010","article-title":"Mathematical modeling of viral kinetics under immune control during primary HIV-1 infection","volume":"259","author":"D Burg","year":"2009","journal-title":"J Theor Biol"},{"issue":"9","key":"ref36","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.1128\/JVI.78.9.4866-4875.2004","article-title":"Roles of target cells and virus-specific cellular immunity in primary simian immunodeficiency virus infection","volume":"78","author":"RR Regoes","year":"2004","journal-title":"Journal of virology"},{"issue":"24","key":"ref37","doi-asserted-by":"crossref","first-page":"12449","DOI":"10.1128\/JVI.01708-08","article-title":"Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia","volume":"82","author":"GD Tomaras","year":"2008","journal-title":"J Virol"},{"issue":"5","key":"ref38","doi-asserted-by":"crossref","first-page":"e1002721","DOI":"10.1371\/journal.ppat.1002721","article-title":"Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape","volume":"8","author":"KJ Bar","year":"2012","journal-title":"PLoS Pathog"},{"issue":"9","key":"ref39","doi-asserted-by":"crossref","first-page":"e1002200","DOI":"10.1371\/journal.pcbi.1002200","article-title":"Why don't CD8+ T cells reduce the lifespan of SIV-infected cells in vivo?","volume":"7","author":"M Elemans","year":"2011","journal-title":"PLoS Comput Biol"},{"issue":"8","key":"ref40","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1000901","article-title":"Similar impact of CD8+ T cell responses on early virus dynamics during SIV infections of rhesus macaques and sooty mangabeys","volume":"6","author":"RD Kouyos","year":"2010","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"ref41","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0042-6822(03)00015-1","article-title":"Mu-opioid modulation of HIV-1 coreceptor expression and HIV-1 replication","volume":"309","author":"AD Steele","year":"2003","journal-title":"Virology"},{"issue":"7","key":"ref42","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S1471-4906(02)02252-4","article-title":"The role of CCR5 chemokine ligands and antibodies to CCR5 coreceptors in preventing HIV infection","volume":"23","author":"T Lehner","year":"2002","journal-title":"Trends in immunology"},{"issue":"2\u20133","key":"ref43","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S1359-6101(00)00033-2","article-title":"Human immunodeficiency virus type-1 and chemokines: beyond competition for common cellular receptors","volume":"12","author":"TS Stantchev","year":"2001","journal-title":"Cytokine & growth factor reviews"},{"issue":"9","key":"ref44","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1084\/jem.185.9.1681","article-title":"CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro","volume":"185","author":"L Wu","year":"1997","journal-title":"J Exp Med"},{"issue":"3","key":"ref45","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1080\/13550280902913628","article-title":"Morphine enhances Tat-induced activation in murine microglia","volume":"15","author":"SM Bokhari","year":"2009","journal-title":"J Neurovirology"},{"issue":"3","key":"ref46","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.clim.2005.02.004","article-title":"Morphine modulates chemokine gene regulation in normal human astrocytes","volume":"115","author":"SD Mahajan","year":"2005","journal-title":"Clinical Immunology"},{"key":"ref47","article-title":"Model Selection and Multimodel Inference: A Practical Information-Theoretic Approach","author":"KP Burnham","year":"2002"},{"issue":"9192","key":"ref48","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1016\/S0140-6736(99)02035-8","article-title":"Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis","volume":"354","author":"B Ramratnam","year":"1999","journal-title":"Lancet"},{"issue":"10","key":"ref49","doi-asserted-by":"crossref","first-page":"5271","DOI":"10.1128\/JVI.76.10.5271-5273.2002","article-title":"The liver is a major organ for clearing simian immunodeficiency virus in rhesus monkeys","volume":"76","author":"L Zhang","year":"2002","journal-title":"J Virol"},{"issue":"8","key":"ref50","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1084\/jem.187.8.1295","article-title":"Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen","volume":"187","author":"N Sachsenberg","year":"1998","journal-title":"J Exp Med"},{"issue":"48","key":"ref51","doi-asserted-by":"crossref","first-page":"19079","DOI":"10.1073\/pnas.0707449104","article-title":"Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques","volume":"104","author":"HY Chen","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"issue":"8","key":"ref52","doi-asserted-by":"crossref","first-page":"5037","DOI":"10.1128\/JVI.77.8.5037-5038.2003","article-title":"A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo","volume":"77","author":"M Markowitz","year":"2003","journal-title":"J Virol"},{"issue":"7","key":"ref53","doi-asserted-by":"crossref","first-page":"3288","DOI":"10.1128\/JVI.02423-08","article-title":"High specific infectivity of plasma virus from the pre-ramp-up and ramp-up stages of acute simian immunodeficiency virus infection","volume":"83","author":"ZM Ma","year":"2009","journal-title":"J Virol"},{"key":"ref54","article-title":"Berkeley Madonna, version 8.3.18","author":"RI Macey","year":"2001"},{"key":"ref55","doi-asserted-by":"crossref","DOI":"10.1002\/9780470316757","article-title":"Nonlinear regression analysis: Its applications","author":"DM Bates","year":"1988"},{"key":"ref56","article-title":"An introduction to the bootstrap","author":"B Efron","year":"1998"},{"issue":"4","key":"ref57","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s11481-008-9127-1","article-title":"CCL5\/RANTES gene deletion attenuates opioid-induced increases in glial CCL2\/MCP-1 immunoreactivity and activation in HIV-1 Tat-exposed mice","volume":"3","author":"N El-Hage","year":"2008","journal-title":"J Neuroimmune Pharmacology"},{"issue":"1\u20132","key":"ref58","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0165-5728(00)00315-5","article-title":"Role of MIP-1beta and RANTES in HIV-1 infection of microglia: inhibition of infection and induction by IFNbeta","volume":"110","author":"R Kitai","year":"2000","journal-title":"J Neuroimmunology"},{"issue":"5","key":"ref59","first-page":"1459","article-title":"Chemokine expression in simian immunodeficiency virus-induced AIDS encephalitis","volume":"149","author":"VG Sasseville","year":"1996","journal-title":"Amer J Pathol"},{"issue":"1\u20132","key":"ref60","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jneuroim.2013.09.013","article-title":"Effect of chronic morphine administration on circulating T cell population dynamics in rhesus macaques","volume":"265","author":"WD Cornwell","year":"2013","journal-title":"J Neuroimmunol"},{"issue":"2","key":"ref61","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0092-8674(02)00832-2","article-title":"The HIV-1 vaccine race","volume":"110","author":"DD Ho","year":"2002","journal-title":"Cell"},{"key":"ref62","article-title":"Multidisciplinary approaches to theory in medicine","author":"RM Ribeiro","year":"2006"},{"issue":"6","key":"ref63","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1086\/368164","article-title":"Determining the relative efficacy of highly active antiretroviral therapy","volume":"187","author":"M Louie","year":"2003","journal-title":"J Infect Dis"},{"issue":"40","key":"ref64","doi-asserted-by":"crossref","first-page":"31305","DOI":"10.1074\/jbc.M001269200","article-title":"Morphine induces gene expression of CCR5 in human CEMx174 lymphocytes","volume":"275","author":"T Miyagi","year":"2000","journal-title":"The Journal of biological chemistry"},{"issue":"12","key":"ref65","doi-asserted-by":"crossref","first-page":"6096","DOI":"10.1128\/JVI.00127-10","article-title":"Estimation of the initial viral growth rate and basic reproductive number during acute HIV-1 infection","volume":"84","author":"RM Ribeiro","year":"2010","journal-title":"J Virol"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T07:55:45Z","timestamp":1601106945000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005127"}},"subtitle":[],"editor":[{"given":"Becca","family":"Asquith","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,9,26]]},"references-count":65,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2016,9,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1005127","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,26]]}}}