%PDF-1.3 % 1 0 obj << /Type /Pages /Count 1 /Kids [ 3 0 R ] >> endobj 2 0 obj << /Producer (PyPDF2) /Title (Microbial\040translocation\040is\040a\040cause\040of\040systemic\040immune\040activation\040in\040chronic\040HIV\040infection) /Author (Jason\040M\056\040Brenchley\054\040David\040Price\054\040Timothy\040W\056\040Schacker\054\040Tedi\040E\056\040Asher\054\040Guido\040Silvestri\054\040Srinivas\040S\056\040Rao\054\040Zachary\040Kazzaz\054\040Ethan\040Bornstein\054\040Olivier\040Lambotte\054\040Daniel\040M\056\040Altmann\054\040Bruce\040R\056\040Blazar\054\040Benigno\040Rodriguez\054\040Leia\040Teixeira\055Johnson\054\040Alan\040L\056\040Landay\054\040Jeffrey\040N\056\040Martin\054\040Frederick\040Hecht\054\040Louis\040J\056\040Picker\054\040Michael\040M\056\040Lederman\054\040Steven\040G\056\040Deeks\054\040Daniel\040C\056\040Douek) /Subject (Chronic\040activation\040of\040the\040immune\040system\040is\040a\040hallmark\040of\040progressive\040HIV\040infection\040and\040better\040predicts\040disease\040outcome\040than\040plasma\040viral\040load\054\040yet\040its\040etiology\040remains\040obscure\056\040Here\040we\040show\040that\040circulating\040microbial\040products\054\040probably\040derived\040from\040the\040gastrointestinal\040tract\054\040are\040a\040cause\040of\040HIV\055related\040systemic\040immune\040activation\056\040Circulating\040lipopolysaccharide\054\040which\040we\040used\040as\040an\040indicator\040of\040microbial\040translocation\054\040was\040significantly\040increased\040in\040chronically\040HIV\055infected\040individuals\040and\040in\040simian\040immunodeficiency\040virus\040\050SIV\051\055infected\040rhesus\040macaques\040\050P\040\074or\075\0400\056002\051\056\040We\040show\040that\040increased\040lipopolysaccharide\040is\040bioactive\040in\040vivo\040and\040correlates\040with\040measures\040of\040innate\040and\040adaptive\040immune\040activation\056\040Effective\040antiretroviral\040therapy\040seemed\040to\040reduce\040microbial\040translocation\040partially\056\040Furthermore\054\040in\040nonpathogenic\040SIV\040infection\040of\040sooty\040mangabeys\054\040microbial\040translocation\040did\040not\040seem\040to\040occur\056\040These\040data\040establish\040a\040mechanism\040for\040chronic\040immune\040activation\040in\040the\040context\040of\040a\040compromised\040gastrointestinal\040mucosal\040surface\040and\040provide\040new\040directions\040for\040therapeutic\040interventions\040that\040modify\040the\040consequences\040of\040acute\040HIV\040infection\056) /Keywords (19\040Nov\0402006\054\040Nature\040Medicine\054\040Immune\040system\054\040Simian\040immunodeficiency\040virus\054\040National\040Institutes\040of\040Health\054\040University\040of\040Minnesota\054\040University\040of\040Pennsylvania\054\040Hammersmith\040Hospital\054\040Case\040Western\040Reserve\040University\054\040Rush\040University\040Medical\040Center\054\040University\040of\040California\054\040San\040Francisco\054\040Oregon\040Health\040\046\040Science\040University) >> endobj 3 0 obj << /CropBox [ 1 0 611 793 ] /Annots [ 16 0 R 17 0 R ] /Parent 1 0 R /Contents 18 0 R /Rotate 0 /MediaBox [ 0 0 612 792 ] /Thumb 19 0 R /Resources 22 0 R /Type /Page >> endobj 4 0 obj << /D [ 3 0 R /XYZ null null null ]/S /GoTo >> endobj 5 0 obj << /Dests 6 0 R >> endobj 6 0 obj << /Names [ (F) 4 0 R (G1003815) 7 0 R (G1010634) 8 0 R (I1\0561010538) 9 0 R (I1\0561010540) 10 0 R (I1\0561010636) 11 0 R (I1\0561010729) 12 0 R (L) 13 0 R (P\0561) 14 0 R ] >> endobj 7 0 obj << /D [ 3 0 R /XYZ 55 710 null ]/S /GoTo >> endobj 8 0 obj << /D [ 3 0 R /XYZ 55 607 null ]/S /GoTo >> endobj 9 0 obj << /D [ 3 0 R /XYZ 55 719 null ]/S /GoTo >> endobj 10 0 obj << /D [ 3 0 R /XYZ 55 719 null ]/S /GoTo >> endobj 11 0 obj << /D [ 3 0 R /XYZ 146 613 null ]/S /GoTo >> endobj 12 0 obj << /D [ 3 0 R /XYZ 186 561 null ]/S /GoTo >> endobj 13 0 obj << /D [ 3 0 R /XYZ null null null ]/S /GoTo >> endobj 14 0 obj << /D [ 3 0 R /XYZ null null null ]/S /GoTo >> endobj 15 0 obj << /Type /Catalog /Pages 1 0 R /Names 5 0 R >> endobj 16 0 obj << /Rect [ 508.487 740.459 574.326 769.529 ] /Subtype /Link /A << /URI (http\072\057\057www\056biomedcentral\056com\057) /S /URI >> /Border [ 0 0 0 ] /Type /Annot >> endobj 17 0 obj << /Rect [ 500.389 692.795 583.134 710.388 ] /Subtype /Link /A << /URI (http\072\057\057www\056biomedcentral\056com\057info\057about\057charter\057) /S /URI >> /Border [ 0 0 0 ] /Type /Annot >> endobj 18 0 obj << /Filter /FlateDecode /Length 3420 >> stream HWْ6}WtIl]%=T9[qy`SBR.)y)U77.͘z~cݭa\Q"0DJ8u"*^oWwu_aZDB%e$EDD!\aYsGFaE$q_E(RW~^׶t5ʂ0W)H۷+pݽftIc(% NJ^9.ߘn]:Lu U] ':Ek/20 HQ)j0Umu2ouږ;r[T=6FqL4E7!M*y0 ߋ slS>% ˌM¸PZ21$O!(@]AOfJx]O'LiNH,+6gat~4㧀&+aD)eX 1 C^ Hh;\45<#/OxA3 ?\Qd - 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