Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens
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{"title"=>"Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens", "type"=>"journal", "authors"=>[{"first_name"=>"Gert U.", "last_name"=>"Van Zyl", "scopus_author_id"=>"6602148482"}, {"first_name"=>"Tommy F.", "last_name"=>"Liu", "scopus_author_id"=>"8599067400"}, {"first_name"=>"Mathilda", "last_name"=>"Claassen", "scopus_author_id"=>"24068796200"}, {"first_name"=>"Susan", "last_name"=>"Engelbrecht", "scopus_author_id"=>"7006812246"}, {"first_name"=>"Tulio", "last_name"=>"de Oliveira", "scopus_author_id"=>"8897715800"}, {"first_name"=>"Wolfgang", "last_name"=>"Preiser", "scopus_author_id"=>"7004338253"}, {"first_name"=>"Natasha T.", "last_name"=>"Wood", "scopus_author_id"=>"16178614000"}, {"first_name"=>"Simon", "last_name"=>"Travers", "scopus_author_id"=>"8617479200"}, {"first_name"=>"Robert W.", "last_name"=>"Shafer", "scopus_author_id"=>"7102887874"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84879487227", "pmid"=>"23840622", "sgr"=>"84879487227", "doi"=>"10.1371/journal.pone.0067188", "isbn"=>"1932-6203", "issn"=>"19326203", "pui"=>"369200496"}, "id"=>"e3d41b73-6548-346f-8697-858ad4998ce2", "abstract"=>"OBJECTIVES: South Africa's national antiretroviral (ARV) treatment program expanded in 2010 to include the nucleoside reverse transcriptase (RT) inhibitors (NRTI) tenofovir (TDF) for adults and abacavir (ABC) for children. We investigated the associated changes in genotypic drug resistance patterns in patients with first-line ARV treatment failure since the introduction of these drugs, and protease inhibitor (PI) resistance patterns in patients who received ritonavir-boosted lopinavir (LPV/r)-containing therapy.\\n\\nMETHODS: We analysed ARV treatment histories and HIV-1 RT and protease mutations in plasma samples submitted to the Tygerberg Academic Hospital National Health Service Laboratory.\\n\\nRESULTS: Between 2006 and 2012, 1,667 plasma samples from 1,416 ARV-treated patients, including 588 children and infants, were submitted for genotypic resistance testing. Compared with 720 recipients of a d4T or AZT-containing first-line regimen, the 153 recipients of a TDF-containing first-line regimen were more likely to have the RT mutations K65R (46% vs 4.0%; p<0.001), Y115F (10% vs. 0.6%; p<0.001), L74VI (8.5% vs. 1.8%; p<0.001), and K70EGQ (7.8% vs. 0.4%) and recipients of an ABC-containing first-line regimen were more likely to have K65R (17% vs 4.0%; p<0.001), Y115F (30% vs 0.6%; p<0.001), and L74VI (56% vs 1.8%; p<0.001). Among the 490 LPV/r recipients, 55 (11%) had ≥1 LPV-resistance mutations including 45 (9.6%) with intermediate or high-level LPV resistance. Low (20 patients) and intermediate (3 patients) darunavir (DRV) cross resistance was present in 23 (4.6%) patients.\\n\\nCONCLUSIONS: Among patients experiencing virological failure on a first-line regimen containing two NRTI plus one NNRTI, the use of TDF in adults and ABC in children was associated with an increase in four major non- thymidine analogue mutations. In a minority of patients, LPV/r-use was associated with intermediate or high-level LPV resistance with predominantly low-level DRV cross-resistance.", "link"=>"http://www.mendeley.com/research/trends-genotypic-hiv1-antiretroviral-resistance-between-2006-2012-south-african-patients-receiving-f", "reader_count"=>59, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>6, "Librarian"=>1, "Student > Doctoral Student"=>6, "Researcher"=>9, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>9, "Other"=>4, "Student > Master"=>6, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>6, "Librarian"=>1, "Student > Doctoral Student"=>6, "Researcher"=>9, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>9, "Other"=>4, "Student > Master"=>6, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>3, "Mathematics"=>2, "Medicine and Dentistry"=>35, "Agricultural and Biological Sciences"=>9, "Social Sciences"=>4, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>35}, "Social Sciences"=>{"Social Sciences"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Brazil"=>1, "Kenya"=>1, "Switzerland"=>1, "Spain"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1102119"], "description"=>"<p>Footnote: *No.: Number of patients receiving first-line therapy with the ARV regimen indicated in the first two columns.</p>†<p>Although M184V/I is a discriminatory mutation it is shown separately because it is the single most common mutation.</p>§<p>The proportion of individuals receiving a thymidine analog (d4T or AZT) or non-thymidine analog (TDF or ABC) based regimen having the indicated mutation. Mutations for which there were statistically significant differences between these proportions are in bold, *p≤0.01, **p≤0.001.</p>", "links"=>[], "tags"=>["Evolutionary biology", "microbiology", "Virology", "antivirals", "Mechanisms of resistance and susceptibility", "Diagnostic medicine", "epidemiology", "Infectious disease epidemiology", "Molecular epidemiology", "Infectious diseases", "Viral diseases", "hiv", "rt", "inhibitor", "percent", "occurrence", "patients", "treated", "dual", "nrti", "nonnucleoside", "first-line", "antiretroviral"], "article_id"=>732341, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Gert U. Van Zyl", "Tommy F. Liu", "Mathilda Claassen", "Susan Engelbrecht", "Tulio de Oliveira", "Wolfgang Preiser", "Natasha T. Wood", "Simon Travers", "Robert W. Shafer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067188.t003", "stats"=>{"downloads"=>4, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nucleoside_RT_Inhibitor_NRTI_Resistance_Mutations_Percent_Occurrence_in_Patients_Treated_with_Dual_NRTI_plus_Nonnucleoside_RT_Inhibitor_NNRTI_First_Line_Antiretroviral_ARV_Regimens_/732341", "title"=>"Nucleoside RT Inhibitor (NRTI) Resistance Mutations: Percent Occurrence in Patients Treated with Dual NRTI plus Nonnucleoside RT Inhibitor (NNRTI) First-Line Antiretroviral (ARV) Regimens.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 09:01:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1102118"], "description"=>"<p>Footnote: *For patients with more than one sample, the age of the patient at the time of the first sample and the year and treatment of the last sample were used.</p>†<p>The patients receiving EFV and LPV/r included those receiving these ARVs as part of separate regimens and those receiving these as part of salvage therapy.</p><p>Misc: Miscellaneous refers to other (rare) NRTI combinations.</p>", "links"=>[], "tags"=>["Evolutionary biology", "microbiology", "Virology", "antivirals", "Mechanisms of resistance and susceptibility", "Diagnostic medicine", "epidemiology", "Infectious disease epidemiology", "Molecular epidemiology", "Infectious diseases", "Viral diseases", "hiv", "antiretroviral", "treatments", "patients", "undergoing", "hiv-1", "genotypic"], "article_id"=>732340, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Gert U. Van Zyl", "Tommy F. Liu", "Mathilda Claassen", "Susan Engelbrecht", "Tulio de Oliveira", "Wolfgang Preiser", "Natasha T. Wood", "Simon Travers", "Robert W. Shafer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067188.t002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_and_Antiretroviral_Treatments_of_1_416_Patients_Undergoing_HIV_1_Genotypic_Resistance_Testing_2006_8211_2012_/732340", "title"=>"Demographic and Antiretroviral Treatments of 1,416 Patients Undergoing HIV-1 Genotypic Resistance Testing, 2006–2012.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 09:01:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1102115"], "description"=>"<p>The median genetic distance between sequences from the same patient was 1.5% (95% range: 0.1% to 7.5%).</p>", "links"=>[], "tags"=>["Evolutionary biology", "microbiology", "Virology", "antivirals", "Mechanisms of resistance and susceptibility", "Diagnostic medicine", "epidemiology", "Infectious disease epidemiology", "Molecular epidemiology", "Infectious diseases", "Viral diseases", "hiv", "uncorrected", "sequences"], "article_id"=>732337, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Gert U. Van Zyl", "Tommy F. Liu", "Mathilda Claassen", "Susan Engelbrecht", "Tulio de Oliveira", "Wolfgang Preiser", "Natasha T. Wood", "Simon Travers", "Robert W. Shafer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067188.g002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_distribution_of_uncorrected_genetic_distance_between_the_sequences_from_the_same_patient_/732337", "title"=>"The distribution of uncorrected genetic distance between the sequences from the same patient.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 09:01:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1102114"], "description"=>"<p>The median uncorrected genetic distance for sequences from different patients was 7.4% (95% range: 5.4% to 11.1%).</p>", "links"=>[], "tags"=>["Evolutionary biology", "microbiology", "Virology", "antivirals", "Mechanisms of resistance and susceptibility", "Diagnostic medicine", "epidemiology", "Infectious disease epidemiology", "Molecular epidemiology", "Infectious diseases", "Viral diseases", "hiv", "uncorrected", "sequences"], "article_id"=>732336, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Gert U. Van Zyl", "Tommy F. Liu", "Mathilda Claassen", "Susan Engelbrecht", "Tulio de Oliveira", "Wolfgang Preiser", "Natasha T. Wood", "Simon Travers", "Robert W. Shafer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067188.g001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_distribution_of_uncorrected_genetic_distance_between_sequences_of_different_patients_/732336", "title"=>"The distribution of uncorrected genetic distance between sequences of different patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 09:01:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1102120"], "description"=>"1<p>D4T could be substituted for AZT in case of toxicity; EFV or NVP chosen dependent on pregnancy risk, EFV chosen when patients receive concurrent rifampicin for tuberculosis. Over time a gradual move to prefer EFV as data suggest that risk to foetus is small. 3TDF replaced by AZT if contra-indicated (e.g. kidney disease). 4Based on data that most children with virologic failuire of a LPV/r first-line regimen have inadequate adherence and no LPV associated resistance, blanket switching is not indicated.</p><p>Patients who were still on D4T by the time of the 2010 regimen guidelines could remain on D4T if they did not experience toxicity. However, practically the threshold for switching for lypodystrophy or other side effects is generally low.</p>", "links"=>[], "tags"=>["Evolutionary biology", "microbiology", "Virology", "antivirals", "Mechanisms of resistance and susceptibility", "Diagnostic medicine", "epidemiology", "Infectious disease epidemiology", "Molecular epidemiology", "Infectious diseases", "Viral diseases", "hiv", "african", "antiretroviral", "guidelines", "2004"], "article_id"=>732342, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Gert U. Van Zyl", "Tommy F. Liu", "Mathilda Claassen", "Susan Engelbrecht", "Tulio de Oliveira", "Wolfgang Preiser", "Natasha T. Wood", "Simon Travers", "Robert W. Shafer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067188.t001", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_South_African_National_Antiretroviral_Therapy_Guidelines_2004_and_2010_/732342", "title"=>"South African National Antiretroviral Therapy Guidelines 2004 and 2010.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 09:01:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1102117"], "description"=>"<p>Footnote: *36 patterns of PI-resistance mutations from 55 patients.</p>†<p>PI-resistance mutations included L10F, L24I, L33F, V32I, M46I/L, I50V, I54V, L76V, V82A, I84V, L89V, and L90M. (D30N, I47V, G48V, I50L, I54L/M/T/A/S, and V82T/S/F did not occur in this dataset). V82M and V82C occurred in 2 patients and were represented by V82A. The accessory mutations L10I/V and A71V/T occurred commonly but are not shown. The mutations V11I, F53L, G73S, T74P, N83D, and N88S each occurred in 1 to 3 patients and are also not shown.</p>§<p>Predicted reduced susceptibility to lopinavir/r (LPV), atazanavir/r (ATV), and darunavir/r (DRV) according to the HIVDB drug-resistance interpretation system. Scores ≥60 indicate high-level resistance; scores between 30 and 59, intermediate resistance; scores between 15 and 29, low-level resistance.</p>¶<p>One of more samples with this pattern of study-defined LPVr mutations had additional PI-resistance mutations that influenced the extent of ATVr cross resistance. For example, the sample with I47A also had the mutation N88S which is associated with high-level ATVr resistance.</p>", "links"=>[], "tags"=>["Evolutionary biology", "microbiology", "Virology", "antivirals", "Mechanisms of resistance and susceptibility", "Diagnostic medicine", "epidemiology", "Infectious disease epidemiology", "Molecular epidemiology", "Infectious diseases", "Viral diseases", "hiv", "inhibitor", "mutation", "patterns", "viruses", "patients", "pi"], "article_id"=>732339, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Gert U. Van Zyl", "Tommy F. Liu", "Mathilda Claassen", "Susan Engelbrecht", "Tulio de Oliveira", "Wolfgang Preiser", "Natasha T. Wood", "Simon Travers", "Robert W. Shafer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067188.t005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protease_Inhibitor_PI_Resistance_Mutation_Patterns_in_Viruses_From_Patients_Receiving_Lopinavir_r_and_their_Predicted_Effect_on_PI_Cross_Resistance_/732339", "title"=>"Protease Inhibitor (PI)-Resistance Mutation Patterns in Viruses From Patients Receiving Lopinavir/r and their Predicted Effect on PI Cross Resistance*.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 09:01:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/1102116"], "description"=>"<p>Footnote: *No.: Number of patients receiving first-line therapy with the ARV regimen indicated in the first two columns.</p>†<p>The proportion of individuals treated with NVP or EFV. Mutations for which there were statistically significant differences according to the NNRTI received: **p≤0.001.</p><p>Fewer sequences were included in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067188#pone-0067188-t004\" target=\"_blank\">table 4</a> than in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067188#pone-0067188-t003\" target=\"_blank\">table 3</a> as sequences that terminated between positions 219 and 229 were excluded from the numerator and denominator for NNRTI mutation statistics.</p>", "links"=>[], "tags"=>["Evolutionary biology", "microbiology", "Virology", "antivirals", "Mechanisms of resistance and susceptibility", "Diagnostic medicine", "epidemiology", "Infectious disease epidemiology", "Molecular epidemiology", "Infectious diseases", "Viral diseases", "hiv", "rt", "inhibitor", "percent", "occurrence", "patients", "treated", "dual", "nucleoside", "nnrti", "antiretroviral"], "article_id"=>732338, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Gert U. Van Zyl", "Tommy F. Liu", "Mathilda Claassen", "Susan Engelbrecht", "Tulio de Oliveira", "Wolfgang Preiser", "Natasha T. Wood", "Simon Travers", "Robert W. Shafer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067188.t004", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nonnucleoside_RT_Inhibitor_NNRTI_Resistance_Mutations_Percent_Occurrence_in_Patients_Treated_with_Dual_nucleoside_RT_inhibitor_NRTI_plus_NNRTI_First_Line_Antiretroviral_ARV_Regimens_/732338", "title"=>"Nonnucleoside RT Inhibitor (NNRTI) Resistance Mutations: Percent Occurrence in Patients Treated with Dual nucleoside RT inhibitor (NRTI) plus NNRTI First Line Antiretroviral (ARV) Regimens.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 09:01:18"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"2", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"4", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Medicine and health sciences/Pathology and laboratory medicine", "average_usage"=>[267, 466, 592, 709, 806, 901, 989, 1075, 1162, 1254, 1342, 1424, 1486]}, {"subject_area"=>"/People and places", "average_usage"=>[270, 456, 573, 676, 773, 867, 955, 1037, 1120, 1205, 1286, 1363, 1436]}, {"subject_area"=>"/People and places/Population groupings", "average_usage"=>[265, 456, 578, 682, 782, 881, 965, 1053, 1133, 1223, 1310, 1391, 1457]}]}
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