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{"title"=>"\"Dynamic range\" of inferred phenotypic HIV drug resistance values in clinical practice", "type"=>"journal", "authors"=>[{"first_name"=>"Luke C.", "last_name"=>"Swenson", "scopus_author_id"=>"25629830200"}, {"first_name"=>"Graham", "last_name"=>"Pollock", "scopus_author_id"=>"40661696500"}, {"first_name"=>"Brian", "last_name"=>"Wynhoven", "scopus_author_id"=>"6603489869"}, {"first_name"=>"Theresa", "last_name"=>"Mo", "scopus_author_id"=>"7005120384"}, {"first_name"=>"Winnie", "last_name"=>"Dong", "scopus_author_id"=>"7202223739"}, {"first_name"=>"Robert S.", "last_name"=>"Hogg", "scopus_author_id"=>"7201804367"}, {"first_name"=>"Julio S.G.", "last_name"=>"Montaner", "scopus_author_id"=>"7202587142"}, {"first_name"=>"P. Richard", "last_name"=>"Harrigan", "scopus_author_id"=>"7004857656"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "sgr"=>"79952094581", "doi"=>"10.1371/journal.pone.0017402", "scopus"=>"2-s2.0-79952094581", "pui"=>"361341362", "pmid"=>"21390218"}, "id"=>"bbeae1b7-d775-3c17-a326-ac9c72b403eb", "abstract"=>"Background: Virtual or inferred phenotypes (vPhenotypes) are commonly used to assess resistance to antiretroviral agents in patients failing therapy. In this study, we provide a clinical context for understanding vPhenotype values. Methods: All HIV-infected persons enrolled in the British Columbia Drug Treatment Program with a baseline plasma viral load (pVL) and follow-up genotypic resistance and pVL results were included up to October 29, 2008 (N=5,277). Change from baseline pVL was determined as a function of Virco vPhenotype, and the dynamic range (defined here by the 10th and 90th percentiles for fold-change in IC50 amongst all patients) was estimated from the distribution of vPhenotye fold-changes across the cohort. Results: The distribution of vPhenotypes from a large cohort of HIV patients who have failed therapy are presented for all available antiretroviral agents. A maximum change in IC50 of at least 13-fold was observed for all drugs. The dideoxy drugs, tenofovir and most PIs exhibited small dynamic ranges with values of 99% of samples. In contrast, zidovudine, lamivudine, emtricitabine and the non-nucleoside reverse transcriptase inihibitors (excluding etravirine) had large dynamic ranges. Conclusion: We describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner.", "link"=>"http://www.mendeley.com/research/dynamic-range-inferred-phenotypic-hiv-drug-resistance-values-clinical-practice", "reader_count"=>13, "reader_count_by_academic_status"=>{"Researcher"=>4, "Student > Ph. D. Student"=>3, "Student > Master"=>3, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>4, "Student > Ph. D. Student"=>3, "Student > Master"=>3, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Mathematics"=>1, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Mathematics"=>{"Mathematics"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Brazil"=>1}, "group_count"=>0}

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• http://doi.org/10.1097/QAD.0000000000000203
• http://doi.org/10.1371/journal.pone.0049602
• http://doi.org/10.1371/journal.pone.0170420

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/796007"], "description"=>"<p>Dynamic range indicated by italics.</p><p>*A total of 3 drugs have only one biological cut-off (for in vitro susceptibility): FTC, NVP, and EFV.</p><p>AZT – zidovudine, 3TC – lamivudine; ddI – didanosine; d4T – stavudine; ABC – abacavir; FTC – emtricitabine; TDF – tenofovir; NVP – nevirapine; DLV – delavirdine; EFV – efavirenz; ETR – etravirine; /r – ritonavir boosted; IDV – indinavir; RTV – ritonavir; NFV – nelfinavir; SQV – saquinavir; FPV – fosamprenavir; LPV – lopinavir; ATV – atazanavir; TPV – tipranavir; DRV – darunavir.</p>", "links"=>[], "tags"=>["susceptibility", "antiretroviral", "agents", "bc"], "article_id"=>466368, "categories"=>["Virology", "Biotechnology", "Genetics", "Infectious Diseases", "Pharmacology"], "users"=>["Luke C. Swenson", "Graham Pollock", "Brian Wynhoven", "Theresa Mo", "Winnie Dong", "Robert S. Hogg", "Julio S. G. Montaner", "P. Richard Harrigan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017402.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HIV_susceptibility_to_antiretroviral_agents_All_BC_vPhenotypes_/466368", "title"=>"HIV susceptibility to antiretroviral agents (All BC vPhenotypes).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-02-24 01:46:08"}
• {"files"=>["https://ndownloader.figshare.com/files/795517"], "description"=>"<p>The distribution of the vPhenotype value (log transformed) for nucleoside/nucleotide reverse transcriptase inhibitors across samples tested in British Columbia where at least 1 International AIDS Society key mutation was present. Percentiles indicated include every half percentile, as the minimum and maximum values for each agent. AZT  =  zidovudine, 3TC  =  lamivudine, ddI  =  didanosine, d4T  =  stavudine, ABC  =  abacavir, FTC  =  emtricitabine, TDF  =  tenofovir. The individual distributions may be grouped into 3 general categories: 3TC/FTC, AZT, and other NRTIs.</p>", "links"=>[], "tags"=>["nrtis", "vphenotypes", "ias"], "article_id"=>465876, "categories"=>["Virology", "Biotechnology", "Genetics", "Infectious Diseases", "Pharmacology"], "users"=>["Luke C. Swenson", "Graham Pollock", "Brian Wynhoven", "Theresa Mo", "Winnie Dong", "Robert S. Hogg", "Julio S. G. Montaner", "P. Richard Harrigan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017402.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_Resistance_to_NRTIs_BC_vPhenotypes_with_1_or_More_IAS_Key_Mutation_/465876", "title"=>"Distribution of Resistance to NRTIs (BC vPhenotypes with 1 or More IAS Key Mutation).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-02-24 01:37:56"}
• {"files"=>["https://ndownloader.figshare.com/files/795768"], "description"=>"<p>The distribution of the vPhenotype value (log transformed) for protease inhibitors across samples tested in British Columbia where at least 1 International AIDS Society key mutation was present. Percentiles indicated include every half percentile, as the minimum and maximum values for each agent. IDV  =  indinavir, RTV  =  ritonavir, NFV  =  nelfinavir, SQV  =  saquinavir, FPV  =  fosamprenavir, ATV  =  atazanavir, TPR  =  tipranavir, DRV  =  darunavir, LPV  =  lopinavir.</p>", "links"=>[], "tags"=>["pis", "vphenotypes", "ias"], "article_id"=>466137, "categories"=>["Virology", "Biotechnology", "Genetics", "Infectious Diseases", "Pharmacology"], "users"=>["Luke C. Swenson", "Graham Pollock", "Brian Wynhoven", "Theresa Mo", "Winnie Dong", "Robert S. Hogg", "Julio S. G. Montaner", "P. Richard Harrigan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017402.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_Resistance_to_PIs_BC_vPhenotypes_with_1_or_More_IAS_Key_Mutation_/466137", "title"=>"Distribution of Resistance to PIs (BC vPhenotypes with 1 or More IAS Key Mutation).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-02-24 01:42:17"}
• {"files"=>["https://ndownloader.figshare.com/files/795956"], "description"=>"<p>The drugs DLV and RTV were not included because the Virco clinical cut-offs are not reported for these agents.</p><p>*A total of 3 drugs have only one biological cut-off (for in vitro susceptibility): FTC, NVP, and EFV.</p><p>The category (below, between, above) where a majority of samples fall is bolded for each agent.</p><p>AZT – zidovudine, 3TC – lamivudine; ddI – didanosine; d4T – stavudine; ABC – abacavir; FTC – emtricitabine; TDF – tenofovir; NVP – nevirapine; EFV – efavirenz; ETR – etravirine; /r – ritonavir boosted; IDV – indinavir; NFV – nelfinavir; SQV – saquinavir; FPV – fosamprenavir; LPV – lopinavir; ATV – atazanavir; TPV – tipranavir; DRV – darunavir.</p>", "links"=>[], "tags"=>["patients", "falling", "virco", "cut-offs", "bc", "phenotypes", "ias"], "article_id"=>466313, "categories"=>["Virology", "Biotechnology", "Genetics", "Infectious Diseases", "Pharmacology"], "users"=>["Luke C. Swenson", "Graham Pollock", "Brian Wynhoven", "Theresa Mo", "Winnie Dong", "Robert S. Hogg", "Julio S. G. Montaner", "P. Richard Harrigan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017402.t003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Proportion_of_patients_falling_below_between_and_above_the_Virco_Clinical_Cut_offs_All_BC_Virtual_Phenotypes_with_one_or_more_IAS_Key_mutation_/466313", "title"=>"Proportion of patients falling below, between, and above the Virco Clinical Cut-offs (All BC Virtual Phenotypes with one or more IAS Key mutation).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-02-24 01:45:13"}
• {"files"=>["https://ndownloader.figshare.com/files/397997", "https://ndownloader.figshare.com/files/398048", "https://ndownloader.figshare.com/files/398086"], "description"=>"<div><h3>Background</h3><p>‘Virtual’ or inferred phenotypes (vPhenotypes) are commonly used to assess resistance to antiretroviral agents in patients failing therapy. In this study, we provide a clinical context for understanding vPhenotype values.</p> <h3>Methods</h3><p>All HIV-infected persons enrolled in the British Columbia Drug Treatment Program with a baseline plasma viral load (pVL) and follow-up genotypic resistance and pVL results were included up to October 29, 2008 (N = 5,277). Change from baseline pVL was determined as a function of Virco vPhenotype, and the “dynamic range” (defined here by the 10th and 90th percentiles for fold-change in IC₅₀ amongst all patients) was estimated from the distribution of vPhenotye fold-changes across the cohort.</p> <h3>Results</h3><p>The distribution of vPhenotypes from a large cohort of HIV patients who have failed therapy are presented for all available antiretroviral agents. A maximum change in IC₅₀ of at least 13-fold was observed for all drugs. The dideoxy drugs, tenofovir and most PIs exhibited small “dynamic ranges” with values of <4-fold change observed in >99% of samples. In contrast, zidovudine, lamivudine, emtricitabine and the non-nucleoside reverse transcriptase inihibitors (excluding etravirine) had large dynamic ranges.</p> <h3>Conclusion</h3><p>We describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner.</p> </div>", "links"=>[], "tags"=>["inferred", "phenotypic", "hiv", "values"], "article_id"=>138634, "categories"=>["Cancer", "Genetics", "Biotechnology", "Pharmacology"], "users"=>["Luke C. Swenson", "Graham Pollock", "Brian Wynhoven", "Theresa Mo", "Winnie Dong", "Robert S. Hogg", "Julio S. G. Montaner", "P. Richard Harrigan"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0017402.s001", "https://dx.doi.org/10.1371/journal.pone.0017402.s002", "https://dx.doi.org/10.1371/journal.pone.0017402.s003"], "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dynamic_Range_of_Inferred_Phenotypic_HIV_Drug_Resistance_Values_in_Clinical_Practice/138634", "title"=>"“Dynamic Range” of Inferred Phenotypic HIV Drug Resistance Values in Clinical Practice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-02-24 02:23:54"}
• {"files"=>["https://ndownloader.figshare.com/files/795651"], "description"=>"<p>The distribution of the vPhenotype value (log transformed) for non-nucleoside reverse transcriptase inhibitors across samples tested in British Columbia where at least 1 International AIDS Society key mutation was present. Percentiles indicated include every half percentile, as the minimum and maximum values for each agent. Note that the scale of the horizontal axis extends to 1000 rather than 100 for <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017402#pone-0017402-g001\" target=\"_blank\">Figures 1a and 1c</a>, reflecting the higher maximum fold-change values observed for the NNRTI drug class. NVP  =  nevirapine, DLV  =  delavirdine, EFV  =  efavirenz, ETR  =  etravirine.</p>", "links"=>[], "tags"=>["nnrtis", "vphenotypes", "ias"], "article_id"=>466014, "categories"=>["Virology", "Biotechnology", "Genetics", "Infectious Diseases", "Pharmacology"], "users"=>["Luke C. Swenson", "Graham Pollock", "Brian Wynhoven", "Theresa Mo", "Winnie Dong", "Robert S. Hogg", "Julio S. G. Montaner", "P. Richard Harrigan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017402.g002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_Resistance_to_NNRTIs_BC_vPhenotypes_with_1_or_More_IAS_Key_Mutation_/466014", "title"=>"Distribution of Resistance to NNRTIs (BC vPhenotypes with 1 or More IAS Key Mutation).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-02-24 01:40:14"}
• {"files"=>["https://ndownloader.figshare.com/files/795906"], "description"=>"<p>Dynamic range indicated by italics.</p><p>*A total of 3 drugs have only one biological cut-off (for in vitro susceptibility): FTC, NVP, and EFV.</p><p>AZT – zidovudine, 3TC – lamivudine; ddI – didanosine; d4T – stavudine; ABC – abacavir; FTC – emtricitabine; TDF – tenofovir; NVP – nevirapine; DLV – delavirdine; EFV – efavirenz; ETR – etravirine; /r – ritonavir boosted; IDV – indinavir; RTV – ritonavir; NFV – nelfinavir; SQV – saquinavir; FPV – fosamprenavir; LPV – lopinavir; ATV – atazanavir; TPV – tipranavir; DRV – darunavir.</p>", "links"=>[], "tags"=>["susceptibility", "antiretroviral", "agents", "bc", "vphenotypes", "ias"], "article_id"=>466271, "categories"=>["Virology", "Biotechnology", "Genetics", "Infectious Diseases", "Pharmacology"], "users"=>["Luke C. Swenson", "Graham Pollock", "Brian Wynhoven", "Theresa Mo", "Winnie Dong", "Robert S. Hogg", "Julio S. G. Montaner", "P. Richard Harrigan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0017402.t002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HIV_susceptibility_to_antiretroviral_agents_All_BC_vPhenotypes_with_one_or_more_IAS_Key_mutation_/466271", "title"=>"HIV susceptibility to antiretroviral agents (All BC vPhenotypes with one or more IAS Key mutation).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-02-24 01:44:31"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime