03517e14d1bbcc3b3ed095d9f499ee6e  296604.pdf
21a38b4f084828d7b18602b1aacfa1a164e419d4  296604.pdf
ef22318bad9aee6659dfb235b2244a9fb0bd6950f2f71c13770aaf82fb35359a  296604.pdf

Title:           A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes
Subject:         DOI: 10.1093/ofid/ofad542; Open Forum Infectious Diseases, 10, 11, 2023-10-31.; Abstract:  Background: Suppressed patients with drug-resistant HIV-1 require effective and simple antiretroviral therapy to maintain treatment adherence and viral suppression. Methods: This randomized, open-label, noninferiority, multicenter pilot study involved HIV-infected adults who met the following criteria: confirmed HIV-1 RNA <50 copies/mL for ≥6 months preceding the study randomization, treatment with at least 3 antiretroviral drugs, and a history of drug resistance mutations against at least 2 antiretroviral classes but remaining fully susceptible to darunavir (DRV) and integrase inhibitors. Participants were randomized 1:1 to switch to dolutegravir (DTG; 50 mg once per day) plus DRV boosted with cobicistat (DRV/c; 800/150 mg once per day; 2D group) or continue with their baseline regimen (standard-of-care [SOC] group). The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies
Keywords:        darunavir/cobicistat; dolutegravir; multidrug resistance HIV-1; switch strategy
Author:          José R. Santos
Creator:         Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64
Producer:        PDFlib+PDI 9.0.7p3 (C++/Win64)
CreationDate:    Mon Nov 20 16:14:22 2023 CET
ModDate:         Mon Nov 20 16:26:17 2023 CET
Custom Metadata: yes
Metadata Stream: yes
Tagged:          yes
UserProperties:  no
Suspects:        no
Form:            AcroForm
JavaScript:      no
Pages:           9
Encrypted:       no
Page size:       593.972 x 782.986 pts
Page rot:        0
File size:       531944 bytes
Optimized:       yes
PDF version:     1.6


name                                 type              encoding         emb sub uni object ID
------------------------------------ ----------------- ---------------- --- --- --- ---------
RMMCTS+MinionPro-Regular             Type 1C           Custom           yes yes yes    979  0
SNSEWB+UniversLTStd-BoldCn           Type 1C           Custom           yes yes yes    982  0
KWOPEE+UniversLTStd-LightCn          Type 1C           Custom           yes yes yes    985  0
ITNIGE+MinionPro-BoldIt              Type 1C           Custom           yes yes yes    988  0
FOKVAI+STIXGeneral-Regular           Type 1C           Custom           yes yes yes    991  0
INUTXC+MinionPro-It                  Type 1C           Custom           yes yes yes    994  0
DKBRNR+MinionPro-Bold                Type 1C           Custom           yes yes yes    997  0
RVRSHG+UniversLTStd-LightCnObl       Type 1C           Custom           yes yes yes   1000  0
LEPWDC+UniversLTStd-Cn               Type 1C           Custom           yes yes yes   1003  0
OPUUHQ+UniversLTStd-Black            Type 1C           Custom           yes yes yes     76  0
PQXDPJ+STIXGeneral-Bold              Type 1C           Custom           yes yes yes     96  0
DJJLHK+UniversLTStd-Light            Type 1C           Custom           yes yes yes     94  0
YEBZNU+UniversLTStd-LightObl         Type 1C           Custom           yes yes yes     98  0


Jhove (Rel. 1.28.0, 2023-05-18)
 Date: 2024-07-18 02:37:05 CEST
 RepresentationInformation: 296604.pdf
  ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16)
  LastModified: 2024-07-17 13:30:32 CEST
  Size: 531944
  Format: PDF
  Version: 1.6
  Status: Well-Formed and valid
  SignatureMatches:
   PDF-hul
  MIMEtype: application/pdf
  Profile: Linearized PDF, Tagged PDF
  PDFMetadata: 
   Objects: 0
   FreeObjects: 1
   IncrementalUpdates: 0
   DocumentCatalog: 
    ViewerPreferences: 
     HideToolbar: false
     HideMenubar: false
     HideWindowUI: false
     FitWindow: false
     CenterWindow: false
     DisplayDocTitle: true
     NonFullScreenPageMode: UseNone
     Direction: L2R
     ViewArea: CropBox
     ViewClip: CropBox
     PrintArea: CropBox
     PageClip: CropBox
    PageLayout: OneColumn
    PageMode: UseOutlines
    Language: en
    Outlines: 
     Item: 
      Title: A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes
      Destination: head1
      Children: 
       Item: 
        Title: METHODS
        Destination: secofad542-s0
        Children: 
         Item: 
          Title: Study Design
          Destination: secofad542-s0.1
         Item: 
          Title: Patient Consent and Ethical Statements
          Destination: secofad542-s0.2
         Item: 
          Title: Study Population
          Destination: secofad542-s0.3
         Item: 
          Title: Outcomes
          Destination: secofad542-s0.4
         Item: 
          Title: Statistical Analysis
          Destination: secofad542-s0.5
       Item: 
        Title: RESULTS
        Destination: secofad542-s1
       Item: 
        Title: DISCUSSION
        Destination: secofad542-s2
       Item: 
        Title: Supplementary Data
        Destination: secofad542-s3
       Item: 
        Title: Notes
        Destination: secofad542-s4
       Item: 
        Title: References
        Destination: reflist
   Filters: 
    FilterPipeline: FlateDecode
    FilterPipeline: DCTDecode
   Images: 
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1066
      ImageHeight: 850
      ColorSpace: RGB
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 1333
      ImageHeight: 398
      ColorSpace: RGB
      BitsPerSample: 8
      BitsPerSampleUnit: integer
    Image: 
     NisoImageMetadata: 
      FormatName: image/jpg
      CompressionScheme: JPEG
      ImageWidth: 600
      ImageHeight: 1365
      ColorSpace: RGB
      BitsPerSample: 8
      BitsPerSampleUnit: integer
   Fonts: 
    Type1: 
     Font: 
      BaseFont: PQXDPJ+STIXGeneral-Bold
      FontSubset: true
      FirstChar: 1
      LastChar: 1
      FontDescriptor: 
       FontName: PQXDPJ+STIXGeneral-Bold
       Flags: Nonsymbolic, ForceBold
       FontBBox: -1030, -455, 2000, 1055
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: INUTXC+MinionPro-It
      FontSubset: true
      FirstChar: 1
      LastChar: 22
      FontDescriptor: 
       FontName: INUTXC+MinionPro-It
       Flags: Nonsymbolic, Italic
       FontBBox: -201, -360, 1684, 1002
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: YEBZNU+UniversLTStd-LightObl
      FontSubset: true
      FirstChar: 1
      LastChar: 2
      FontDescriptor: 
       FontName: YEBZNU+UniversLTStd-LightObl
       Flags: Nonsymbolic, Italic
       FontBBox: -151, -274, 1144, 957
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: DKBRNR+MinionPro-Bold
      FontSubset: true
      FirstChar: 1
      LastChar: 24
      FontDescriptor: 
       FontName: DKBRNR+MinionPro-Bold
       Flags: Nonsymbolic, ForceBold
       FontBBox: -318, -360, 1684, 1024
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: RVRSHG+UniversLTStd-LightCnObl
      FontSubset: true
      FirstChar: 1
      LastChar: 20
      FontDescriptor: 
       FontName: RVRSHG+UniversLTStd-LightCnObl
       Flags: Nonsymbolic, Italic
       FontBBox: -169, -271, 1065, 953
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: LEPWDC+UniversLTStd-Cn
      FontSubset: true
      FirstChar: 1
      LastChar: 10
      FontDescriptor: 
       FontName: LEPWDC+UniversLTStd-Cn
       Flags: Nonsymbolic
       FontBBox: -166, -250, 1000, 989
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: OPUUHQ+UniversLTStd-Black
      FontSubset: true
      FirstChar: 1
      LastChar: 28
      FontDescriptor: 
       FontName: OPUUHQ+UniversLTStd-Black
       Flags: Nonsymbolic, ForceBold
       FontBBox: -153, -250, 992, 986
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: RMMCTS+MinionPro-Regular
      FontSubset: true
      FirstChar: 1
      LastChar: 91
      FontDescriptor: 
       FontName: RMMCTS+MinionPro-Regular
       Flags: Nonsymbolic
       FontBBox: -290, -360, 1684, 989
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: SNSEWB+UniversLTStd-BoldCn
      FontSubset: true
      FirstChar: 3
      LastChar: 69
      FontDescriptor: 
       FontName: SNSEWB+UniversLTStd-BoldCn
       Flags: Nonsymbolic, ForceBold
       FontBBox: -83, -250, 1000, 969
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: KWOPEE+UniversLTStd-LightCn
      FontSubset: true
      FirstChar: 1
      LastChar: 83
      FontDescriptor: 
       FontName: KWOPEE+UniversLTStd-LightCn
       Flags: Nonsymbolic
       FontBBox: -163, -250, 1000, 953
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: ITNIGE+MinionPro-BoldIt
      FontSubset: true
      FirstChar: 1
      LastChar: 31
      FontDescriptor: 
       FontName: ITNIGE+MinionPro-BoldIt
       Flags: Nonsymbolic, Italic, ForceBold
       FontBBox: -230, -360, 1684, 1032
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: DJJLHK+UniversLTStd-Light
      FontSubset: true
      FirstChar: 1
      LastChar: 72
      FontDescriptor: 
       FontName: DJJLHK+UniversLTStd-Light
       Flags: Nonsymbolic
       FontBBox: -151, -250, 1000, 957
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: FOKVAI+STIXGeneral-Regular
      FontSubset: true
      FirstChar: 1
      LastChar: 7
      FontDescriptor: 
       FontName: FOKVAI+STIXGeneral-Regular
       Flags: Nonsymbolic
       FontBBox: -995, -455, 2000, 1055
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
   XMP: <x:xmpmeta xmlns:x="adobe:ns:meta/" x:xmptk="Adobe XMP Core 5.4-c006 80.159825, 2016/09/16-03:31:08        ">
   <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about=""
            xmlns:xmpMM="http://ns.adobe.com/xap/1.0/mm/"
            xmlns:xmpRights="http://ns.adobe.com/xap/1.0/rights/"
            xmlns:pdf="http://ns.adobe.com/pdf/1.3/"
            xmlns:dc="http://purl.org/dc/elements/1.1/"
            xmlns:prism="http://prismstandard.org/namespaces/basic/2.0/"
            xmlns:xmp="http://ns.adobe.com/xap/1.0/"
            xmlns:pdfx="http://ns.adobe.com/pdfx/1.3/"
            xmlns:pdfuaid="http://www.aiim.org/pdfua/ns/id/"
            xmlns:pdfaExtension="http://www.aiim.org/pdfa/ns/extension/"
            xmlns:pdfaSchema="http://www.aiim.org/pdfa/ns/schema#"
            xmlns:pdfaProperty="http://www.aiim.org/pdfa/ns/property#">
         <xmpMM:InstanceID>uuid:0372b019-3984-41ad-9277-92e38f58bd3f</xmpMM:InstanceID>
         <xmpMM:DocumentID>uuid:D55ED976-1216-6903-4146-A5CCD88095F8</xmpMM:DocumentID>
         <xmpRights:Marked>True</xmpRights:Marked>
         <pdf:Keywords>darunavir/cobicistat; dolutegravir; multidrug resistance HIV-1; switch strategy</pdf:Keywords>
         <pdf:Producer>PDFlib+PDI 9.0.7p3 (C++/Win64)</pdf:Producer>
         <dc:format>application/pdf</dc:format>
         <dc:identifier>10.1093/ofid/ofad542</dc:identifier>
         <dc:lang>en</dc:lang>
         <dc:publisher>
            <rdf:Bag>
               <rdf:li>Oxford University Press</rdf:li>
            </rdf:Bag>
         </dc:publisher>
         <dc:title>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes</rdf:li>
            </rdf:Alt>
         </dc:title>
         <dc:creator>
            <rdf:Seq>
               <rdf:li>José R. Santos</rdf:li>
               <rdf:li>Pere Domingo</rdf:li>
               <rdf:li>Joaquín Portilla</rdf:li>
               <rdf:li>Félix Gutiérrez</rdf:li>
               <rdf:li>Arkaitz Imaz</rdf:li>
               <rdf:li>Helem Vilchez</rdf:li>
               <rdf:li>Adrià Curran</rdf:li>
               <rdf:li>Nieves Valcarce-Pardeiro</rdf:li>
               <rdf:li>Antoni Payeras</rdf:li>
               <rdf:li>Enrique Bernal</rdf:li>
               <rdf:li>Marta Montero-Alonso</rdf:li>
               <rdf:li>Miguel Yzusqui</rdf:li>
               <rdf:li>Bonaventura Clotet</rdf:li>
               <rdf:li>Sebastià Videla</rdf:li>
               <rdf:li>José Moltó</rdf:li>
               <rdf:li>Roger Paredes</rdf:li>
            </rdf:Seq>
         </dc:creator>
         <dc:description>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">DOI: 10.1093/ofid/ofad542; Open Forum Infectious Diseases, 10, 11, 2023-10-31.; Abstract:  Background: Suppressed patients with drug-resistant HIV-1 require effective and simple antiretroviral therapy to maintain treatment adherence and viral suppression. Methods: This randomized, open-label, noninferiority, multicenter pilot study involved HIV-infected adults who met the following criteria: confirmed HIV-1 RNA &lt;50 copies/mL for ≥6 months preceding the study randomization, treatment with at least 3 antiretroviral drugs, and a history of drug resistance mutations against at least 2 antiretroviral classes but remaining fully susceptible to darunavir (DRV) and integrase inhibitors. Participants were randomized 1:1 to switch to dolutegravir (DTG; 50 mg once per day) plus DRV boosted with cobicistat (DRV/c; 800/150 mg once per day; 2D group) or continue with their baseline regimen (standard-of-care [SOC] group). The primary endpoint was the proportion of patients with HIV-1 RNA &lt;50 copies</rdf:li>
            </rdf:Alt>
         </dc:description>
         <dc:rights>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.</rdf:li>
            </rdf:Alt>
         </dc:rights>
         <dc:subject>
            <rdf:Bag>
               <rdf:li>darunavir/cobicistat</rdf:li>
               <rdf:li>dolutegravir</rdf:li>
               <rdf:li>multidrug resistance HIV-1</rdf:li>
               <rdf:li>switch strategy</rdf:li>
            </rdf:Bag>
         </dc:subject>
         <prism:aggregationType>Journal</prism:aggregationType>
         <prism:publicationName>Open Forum Infectious Diseases</prism:publicationName>
         <prism:copyright>© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.</prism:copyright>
         <prism:issn/>
         <prism:elssn>2328-8957</prism:elssn>
         <prism:volume>10</prism:volume>
         <prism:number>11</prism:number>
         <prism:issueName/>
         <prism:startingPage>1</prism:startingPage>
         <prism:endingPage>9</prism:endingPage>
         <prism:doi>10.1093/ofid/ofad542</prism:doi>
         <prism:url>https://doi.org/10.1093/ofid/ofad542</prism:url>
         <xmp:CreateDate>2023-11-20T20:44:22+05:30</xmp:CreateDate>
         <xmp:ModifyDate>2023-11-20T20:56:17+05:30</xmp:ModifyDate>
         <xmp:CreatorTool>Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64</xmp:CreatorTool>
         <xmp:MetadataDate>2023-11-20T20:56:17+05:30</xmp:MetadataDate>
         <pdfx:EPSprocessor>PStill version 1.84.42</pdfx:EPSprocessor>
         <pdfuaid:part>1</pdfuaid:part>
         <pdfaExtension:schemas>
            <rdf:Bag>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:schema>PDF/UA Universal Accessibility Schema</pdfaSchema:schema>
                  <pdfaSchema:namespaceURI>http://www.aiim.org/pdfua/ns/id/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>pdfuaid</pdfaSchema:prefix>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:name>part</pdfaProperty:name>
                           <pdfaProperty:valueType>Integer</pdfaProperty:valueType>
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Indicates, which part of ISO 14289 standard is followed</pdfaProperty:description>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
            </rdf:Bag>
         </pdfaExtension:schemas>
      </rdf:Description>
   </rdf:RDF>
</x:xmpmeta>
   Pages: 
    Page: 
     Sequence: 1
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 99, 618, 101, 626
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 103, 617, 107, 624
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 157, 618, 160, 626
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 161, 617, 165, 624
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 221, 618, 224, 626
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 276, 618, 279, 626
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 280, 618, 283, 626
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 284, 618, 287, 626
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 331, 618, 334, 626
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 335, 617, 339, 624
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 390, 618, 393, 626
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 439, 618, 442, 626
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 530, 618, 536, 626
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 100, 608, 105, 616
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 158, 608, 164, 616
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 165, 608, 170, 616
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 172, 607, 176, 614
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 254, 608, 260, 616
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 314, 608, 320, 616
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 386, 608, 389, 616
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 390, 608, 396, 616
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 451, 608, 457, 616
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 458, 608, 463, 616
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 504, 608, 507, 616
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 508, 608, 511, 616
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 111, 598, 113, 606
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 115, 598, 120, 606
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 121, 598, 127, 606
       Flags: Print
       Destination: 910
      Annotation: 
       Subtype: Link
       Rect: 50, 136, 98, 143
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 151, 98, 267, 105
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 48, 71, 142, 78
       Flags: Print
    Page: 
     Sequence: 2
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 126, 734, 131, 743
       Flags: Print
       Destination: 24
      Annotation: 
       Subtype: Link
       Rect: 179, 656, 183, 665
       Flags: Print
       Destination: 24
      Annotation: 
       Subtype: Link
       Rect: 188, 656, 193, 665
       Flags: Print
       Destination: 24
      Annotation: 
       Subtype: Link
       Rect: 260, 565, 264, 574
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 151, 539, 160, 548
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 357, 617, 459, 627
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 469, 149, 478, 158
       Flags: Print
       Destination: 27
    Page: 
     Sequence: 3
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 392, 435, 484, 444
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 454, 409, 485, 418
       Flags: Print
       Destination: 7
      Annotation: 
       Subtype: Link
       Rect: 349, 344, 438, 353
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 353, 292, 442, 301
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 306, 226, 392, 236
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 481, 123, 515, 132
       Flags: Print
       Destination: 12
    Page: 
     Sequence: 4
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 309, 500, 337, 509
       Flags: Print
       Destination: 12
      Annotation: 
       Subtype: Link
       Rect: 372, 201, 400, 210
       Flags: Print
       Destination: 16
      Annotation: 
       Subtype: Link
       Rect: 405, 201, 498, 210
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 381, 149, 414, 158
       Flags: Print
       Destination: 16
      Annotation: 
       Subtype: Link
       Rect: 412, 540, 480, 546
       Flags: Print
    Page: 
     Sequence: 5
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 445, 192, 476, 202
       Flags: Print
       Destination: 16
      Annotation: 
       Subtype: Link
       Rect: 327, 153, 359, 163
       Flags: Print
       Destination: 20
      Annotation: 
       Subtype: Link
       Rect: 521, 114, 530, 124
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 462, 88, 471, 98
       Flags: Print
       Destination: 27
    Page: 
     Sequence: 6
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 449, 149, 458, 158
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 463, 149, 472, 158
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 309, 97, 313, 106
       Flags: Print
       Destination: 24
      Annotation: 
       Subtype: Link
       Rect: 318, 97, 323, 106
       Flags: Print
       Destination: 24
      Annotation: 
       Subtype: Link
       Rect: 328, 97, 332, 106
       Flags: Print
       Destination: 24
      Annotation: 
       Subtype: Link
       Rect: 337, 97, 346, 106
       Flags: Print
       Destination: 27
    Page: 
     Sequence: 7
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 115, 84, 119, 93
       Flags: Print
       Destination: 24
      Annotation: 
       Subtype: Link
       Rect: 124, 84, 129, 93
       Flags: Print
       Destination: 24
      Annotation: 
       Subtype: Link
       Rect: 133, 84, 142, 93
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 399, 721, 408, 730
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 413, 721, 422, 730
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 422, 708, 432, 717
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 436, 708, 446, 717
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 378, 682, 387, 691
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 394, 682, 403, 691
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 409, 682, 418, 691
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 530, 669, 539, 678
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 478, 656, 487, 665
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 492, 656, 501, 665
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 332, 630, 341, 639
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 346, 630, 355, 639
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 360, 630, 369, 639
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 468, 422, 472, 431
       Flags: Print
       Destination: 24
      Annotation: 
       Subtype: Link
       Rect: 477, 422, 486, 431
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 491, 422, 500, 431
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 309, 149, 318, 158
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 277, 155, 284, 163
       Flags: Print
       Destination: 27
    Page: 
     Sequence: 8
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 221, 617, 230, 626
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 240, 578, 249, 587
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 87, 565, 96, 574
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 86, 526, 95, 535
       Flags: Print
       Destination: 27
      Annotation: 
       Subtype: Link
       Rect: 56, 358, 136, 366
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 306, 305, 312, 312
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 260, 312, 267
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 233, 312, 240
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 197, 312, 204
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 170, 312, 177
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 134, 312, 141
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 107, 312, 114
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 80, 312, 87
       Flags: Print
       Destination: 1
    Page: 
     Sequence: 9
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 48, 718, 55, 725
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 48, 700, 55, 707
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 48, 673, 55, 680
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 48, 646, 55, 653
       Flags: Print
       Destination: 12
      Annotation: 
       Subtype: Link
       Rect: 48, 619, 55, 626
       Flags: Print
       Destination: 12
      Annotation: 
       Subtype: Link
       Rect: 48, 583, 55, 590
       Flags: Print
       Destination: 16
      Annotation: 
       Subtype: Link
       Rect: 48, 547, 55, 554
       Flags: Print
       Destination: 16
      Annotation: 
       Subtype: Link
       Rect: 48, 520, 55, 527
       Flags: Print
       Destination: 16
      Annotation: 
       Subtype: Link
       Rect: 306, 717, 312, 724
       Flags: Print
       Destination: 20
      Annotation: 
       Subtype: Link
       Rect: 306, 680, 312, 687
       Flags: Print
       Destination: 20
      Annotation: 
       Subtype: Link
       Rect: 306, 652, 312, 659
       Flags: Print
       Destination: 20
      Annotation: 
       Subtype: Link
       Rect: 306, 624, 312, 631
       Flags: Print
       Destination: 20
      Annotation: 
       Subtype: Link
       Rect: 306, 596, 312, 603
       Flags: Print
       Destination: 20
      Annotation: 
       Subtype: Link
       Rect: 306, 568, 312, 574
       Flags: Print
       Destination: 20
      Annotation: 
       Subtype: Link
       Rect: 306, 539, 312, 546
       Flags: Print
       Destination: 20
      Annotation: 
       Subtype: Link
       Rect: 436, 530, 544, 537
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 317, 520, 400, 527
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 306, 511, 312, 518
       Flags: Print
       Destination: 24
      Annotation: 
       Subtype: Link
       Rect: 317, 502, 493, 509
       Flags: Print
  Checksum: af1a02f2
   Type: CRC32
  Checksum: 03517e14d1bbcc3b3ed095d9f499ee6e
   Type: MD5
  Checksum: 21a38b4f084828d7b18602b1aacfa1a164e419d4
   Type: SHA-1
  Checksum: ef22318bad9aee6659dfb235b2244a9fb0bd6950f2f71c13770aaf82fb35359a
   Type: SHA-256