HIV Cure Strategies: How Good Must They Be to Improve on Current Antiretroviral Therapy?
Publication Date
November 14, 2014
Journal
PLOS ONE
Authors
Paul E. Sax, Alexis Sypek, Bethany K. Berkowitz, Bethany L. Morris, et al
Volume
9
Issue
11
Pages
e113031
DOI
https://dx.plos.org/10.1371/journal.pone.0113031
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0113031
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/25397616
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232561
Europe PMC
http://europepmc.org/abstract/MED/25397616
Web of Science
000345558500125
Scopus
84911935103
Mendeley
http://www.mendeley.com/research/hiv-cure-strategies-good-improve-current-antiretroviral-therapy
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Mendeley | Further Information

{"title"=>"HIV cure strategies: How good must they be to improve on current antiretroviral therapy?", "type"=>"journal", "authors"=>[{"first_name"=>"Paul E.", "last_name"=>"Sax", "scopus_author_id"=>"7005478002"}, {"first_name"=>"Alexis", "last_name"=>"Sypek", "scopus_author_id"=>"55839979400"}, {"first_name"=>"Bethany K.", "last_name"=>"Berkowitz", "scopus_author_id"=>"55745067500"}, {"first_name"=>"Bethany L.", "last_name"=>"Morris", "scopus_author_id"=>"35226363900"}, {"first_name"=>"Elena", "last_name"=>"Losina", "scopus_author_id"=>"7003799126"}, {"first_name"=>"A. David", "last_name"=>"Paltiel", "scopus_author_id"=>"7004306826"}, {"first_name"=>"Kathleen A.", "last_name"=>"Kelly", "scopus_author_id"=>"56258062100"}, {"first_name"=>"George R.", "last_name"=>"Seage", "scopus_author_id"=>"7005806301"}, {"first_name"=>"Rochelle P.", "last_name"=>"Walensky", "scopus_author_id"=>"6602540593"}, {"first_name"=>"Milton C.", "last_name"=>"Weinstein", "scopus_author_id"=>"7201568913"}, {"first_name"=>"Joseph", "last_name"=>"Eron", "scopus_author_id"=>"7006154419"}, {"first_name"=>"Kenneth A.", "last_name"=>"Freedberg", "scopus_author_id"=>"7004947755"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"600506858", "sgr"=>"84911935103", "pmid"=>"25397616", "scopus"=>"2-s2.0-84911935103", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0113031", "issn"=>"19326203"}, "id"=>"ee6dc230-cd26-37cd-b2da-31b238878750", "abstract"=>"BACKGROUND: We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART).\\n\\nMETHODS: We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY.\\n\\nRESULTS: For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving.\\n\\nCONCLUSIONS: Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV.", "link"=>"http://www.mendeley.com/research/hiv-cure-strategies-good-improve-current-antiretroviral-therapy", "reader_count"=>28, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Librarian"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>3, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Librarian"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>3, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Nursing and Health Professions"=>3, "Mathematics"=>1, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>6, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Social Sciences"=>1, "Computer Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Computer Science"=>{"Computer Science"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>3}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>5}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Spain"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1794584"], "description"=>"<p>The figure depicts the cost-effectiveness of Stem Cell Transplantation compared to standard of care ART as a function of the three influential parameters identified via the one-way sensitivity analysis in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113031#pone-0113031-t003\" target=\"_blank\">Table 3:</a> cost, relapse rate, and efficacy. In each panel, the horizontal axis denotes efficacy while the vertical axis denotes the relapse rate. Inside each panel, the shading denotes the resultant cost-effectiveness finding, ranging from cost-saving (green), through cost-effective (with an ICER<$100,000/QALY, yellow), to not cost-effective (≥$100,000/QALY or more expensive and less effective than ART, red). Instances where the intervention is both less expensive and less effective than ART are denoted in blue, but most were not cost-effective because the ICER of ART was <$100,000/QALY compared to SCT. The plus sign indicates a strategy that had an ICER for ART compared to SCT >$100,000/QALY gained. <b>ART:</b> antiretroviral therapy; <b>ICER:</b> incremental cost-effectiveness ration; <b>QALY:</b> quality-adjusted life year.</p>", "links"=>[], "tags"=>["qaly", "computer simulation model", "Stem cell transplantation", "HIV Cure Strategies", "sct", "Current Antiretroviral Therapy", "HIV cure interventions", "Moderate efficacy increases", "strategy", "Gene therapy", "chemotherapy", "relapse", "life expectancy", "cure strategies"], "article_id"=>1241691, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Paul E. Sax", "Alexis Sypek", "Bethany K. Berkowitz", "Bethany L. Morris", "Elena Losina", "A. David Paltiel", "Kathleen A. Kelly", "George R. Seage III", "Rochelle P. Walensky", "Milton C. Weinstein", "Joseph Eron", "Kenneth A. Freedberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113031.g003", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stem_Cell_Transplantation_compared_to_standard_of_care_ART_/1241691", "title"=>"Stem Cell Transplantation compared to standard of care ART.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-14 02:42:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1794578"], "description"=>"<p>The figure depicts the cost-effectiveness of Gene Therapy compared to standard of care ART as a function of the three influential parameters identified via the one-way sensitivity analysis in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113031#pone-0113031-t003\" target=\"_blank\">Table 3:</a> cost, relapse rate, and efficacy. In each panel, the horizontal axis denotes efficacy while the vertical axis denotes the relapse rate. Inside each panel, the shading denotes the resultant cost-effectiveness finding, ranging from cost-saving (green), through cost-effective (with an ICER<$100,000/QALY, yellow), to not cost-effective (≥$100,000/QALY or more expensive and less effective than ART, red). <b>ART:</b> antiretroviral therapy; <b>ICER:</b> incremental cost-effectiveness ration; <b>QALY:</b> quality-adjusted life year.</p>", "links"=>[], "tags"=>["qaly", "computer simulation model", "Stem cell transplantation", "HIV Cure Strategies", "sct", "Current Antiretroviral Therapy", "HIV cure interventions", "Moderate efficacy increases", "strategy", "Gene therapy", "chemotherapy", "relapse", "life expectancy", "cure strategies"], "article_id"=>1241685, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Paul E. Sax", "Alexis Sypek", "Bethany K. Berkowitz", "Bethany L. Morris", "Elena Losina", "A. David Paltiel", "Kathleen A. Kelly", "George R. Seage III", "Rochelle P. Walensky", "Milton C. Weinstein", "Joseph Eron", "Kenneth A. Freedberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113031.g001", "stats"=>{"downloads"=>1, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_Therapy_compared_to_standard_of_care_ART_/1241685", "title"=>"Gene Therapy compared to standard of care ART.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-14 02:42:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1794586"], "description"=>"<p><b>SD:</b> standard deviation; <b>QOL:</b> quality-of-life.</p>a<p>Determined through initialization run of simulated cohort; <sup>b</sup>For 24 months based on vorinostat; <sup>c</sup>For monthly antiretroviral therapy, derived from weighted averages of current therapies until gene- or chemo-therapy is complete; <sup>d</sup>For immunosuppressive agents, including methotrexate with tacrolimus.</p><p>Parameter inputs for a model-based analysis of potential HIV cure strategies.</p>", "links"=>[], "tags"=>["qaly", "computer simulation model", "Stem cell transplantation", "HIV Cure Strategies", "sct", "Current Antiretroviral Therapy", "HIV cure interventions", "Moderate efficacy increases", "strategy", "Gene therapy", "chemotherapy", "relapse", "life expectancy", "cure strategies"], "article_id"=>1241693, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Paul E. Sax", "Alexis Sypek", "Bethany K. Berkowitz", "Bethany L. Morris", "Elena Losina", "A. David Paltiel", "Kathleen A. Kelly", "George R. Seage III", "Rochelle P. Walensky", "Milton C. Weinstein", "Joseph Eron", "Kenneth A. Freedberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113031.t001", "stats"=>{"downloads"=>6, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Parameter_inputs_for_a_model_based_analysis_of_potential_HIV_cure_strategies_/1241693", "title"=>"Parameter inputs for a model-based analysis of potential HIV cure strategies.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-14 02:42:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1794580"], "description"=>"<p>The figure depicts the cost-effectiveness of Chemotherapy compared to standard of care ART as a function of the three influential parameters identified via the one-way sensitivity analysis in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113031#pone-0113031-t003\" target=\"_blank\">Table 3:</a> cost, relapse rate, and efficacy. In each panel, the horizontal axis denotes efficacy while the vertical axis denotes the relapse rate. Inside each panel, the shading denotes the resultant cost-effectiveness finding, ranging from cost-saving (green), through cost-effective (with an ICER<$100,000/QALY, yellow), to not cost-effective (≥$100,000/QALY or more expensive and less effective than ART, red). <b>ART:</b> antiretroviral therapy; <b>ICER:</b> incremental cost-effectiveness ration; <b>QALY:</b> quality-adjusted life year.</p>", "links"=>[], "tags"=>["qaly", "computer simulation model", "Stem cell transplantation", "HIV Cure Strategies", "sct", "Current Antiretroviral Therapy", "HIV cure interventions", "Moderate efficacy increases", "strategy", "Gene therapy", "chemotherapy", "relapse", "life expectancy", "cure strategies"], "article_id"=>1241687, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Paul E. Sax", "Alexis Sypek", "Bethany K. Berkowitz", "Bethany L. Morris", "Elena Losina", "A. David Paltiel", "Kathleen A. Kelly", "George R. Seage III", "Rochelle P. Walensky", "Milton C. Weinstein", "Joseph Eron", "Kenneth A. Freedberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113031.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chemotherapy_compared_to_standard_of_care_ART_/1241687", "title"=>"Chemotherapy compared to standard of care ART.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-14 02:42:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1794590"], "description"=>"<p><b>ICER:</b> incremental cost-effectiveness ratio; <b>QALY:</b> quality-adjusted life year; <b>QOL:</b> quality of life; <b>Dominated:</b> strategy was less effective and more expensive than current ART.</p><p>*Cost reductions led to the strategy being less effective and less expensive than current ART. One could calculate an ICER for ART compared to Chemotherapy or Stem Cell Transplant, but it is not clinically plausible that these strategies would be used if they resulted in worse outcomes than standard of care with ART, even if they saved money by avoiding the costs of lifelong ART.</p><p>Threshold which key parameters would need to reach for each type of HIV cure strategy to be cost-effective (ICER<$100,000/QALY gained) or cost-saving.</p>", "links"=>[], "tags"=>["qaly", "computer simulation model", "Stem cell transplantation", "HIV Cure Strategies", "sct", "Current Antiretroviral Therapy", "HIV cure interventions", "Moderate efficacy increases", "strategy", "Gene therapy", "chemotherapy", "relapse", "life expectancy", "cure strategies"], "article_id"=>1241697, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Paul E. Sax", "Alexis Sypek", "Bethany K. Berkowitz", "Bethany L. Morris", "Elena Losina", "A. David Paltiel", "Kathleen A. Kelly", "George R. Seage III", "Rochelle P. Walensky", "Milton C. Weinstein", "Joseph Eron", "Kenneth A. Freedberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113031.t003", "stats"=>{"downloads"=>4, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Threshold_which_key_parameters_would_need_to_reach_for_each_type_of_HIV_cure_strategy_to_be_cost_effective_ICER_lt_100_000_QALY_gained_or_cost_saving_/1241697", "title"=>"Threshold which key parameters would need to reach for each type of HIV cure strategy to be cost-effective (ICER<$100,000/QALY gained) or cost-saving.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-14 02:42:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1794588"], "description"=>"<p>*Based on assumptions for efficacy, durability, toxicity, and cost in Methods and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113031#pone-0113031-t001\" target=\"_blank\">Table 1</a>. Life expectancy, QALYs, and costs all discounted at 3%/year. <b>ART:</b> antiretroviral therapy; <b>QALY:</b> Quality-adjusted life year; <b>Dominated:</b> Less effective and more costly than the standard of care ART strategy.</p><p>Base case results of an analysis of hypothetical HIV cure strategies<sup><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113031#nt103\" target=\"_blank\">*</a></sup>.</p>", "links"=>[], "tags"=>["qaly", "computer simulation model", "Stem cell transplantation", "HIV Cure Strategies", "sct", "Current Antiretroviral Therapy", "HIV cure interventions", "Moderate efficacy increases", "strategy", "Gene therapy", "chemotherapy", "relapse", "life expectancy", "cure strategies"], "article_id"=>1241695, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Paul E. Sax", "Alexis Sypek", "Bethany K. Berkowitz", "Bethany L. Morris", "Elena Losina", "A. David Paltiel", "Kathleen A. Kelly", "George R. Seage III", "Rochelle P. Walensky", "Milton C. Weinstein", "Joseph Eron", "Kenneth A. Freedberg"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0113031.t002", "stats"=>{"downloads"=>4, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Base_case_results_of_an_analysis_of_hypothetical_HIV_cure_strategies_/1241695", "title"=>"Base case results of an analysis of hypothetical HIV cure strategies<sup>*</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-11-14 02:42:07"}

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