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{"title"=>"HIV treatment as prevention: Debate and commentary-will early infection compromise treatment-as-prevention strategies?", "type"=>"journal", "authors"=>[{"first_name"=>"Myron S.", "last_name"=>"Cohen", "scopus_author_id"=>"54790532400"}, {"first_name"=>"Christopher", "last_name"=>"Dye", "scopus_author_id"=>"34770166000"}, {"first_name"=>"Christophe", "last_name"=>"Fraser", "scopus_author_id"=>"35460815100"}, {"first_name"=>"William C.", "last_name"=>"Miller", "scopus_author_id"=>"7406061778"}, {"first_name"=>"Kimberly A.", "last_name"=>"Powers", "scopus_author_id"=>"7006194043"}, {"first_name"=>"Brian G.", "last_name"=>"Williams", "scopus_author_id"=>"55499079300"}], "year"=>2012, "source"=>"PLoS Medicine", "identifiers"=>{"issn"=>"15491277", "scopus"=>"2-s2.0-84864476583", "sgr"=>"84864476583", "pui"=>"365352077", "isbn"=>"1549-1676 (Electronic)\\r1549-1277 (Linking)", "pmid"=>"22802728", "doi"=>"10.1371/journal.pmed.1001232"}, "id"=>"8f7f6b13-3727-39e0-a89d-fd15895b0556", "abstract"=>"Universal HIV testing and immediate antiretroviral therapy for infected individuals has been proposed as a way of reducing the transmission of HIV and thereby bringing the HIV epidemic under control. It is unclear whether transmission during early HIV infection--before individuals are likely to have been diagnosed with HIV and started on antiretroviral therapy--will compromise the effectiveness of treatment as prevention. This article presents two opposing viewpoints by Powers, Miller, and Cohen, and Williams and Dye, followed by a commentary by Fraser.", "link"=>"http://www.mendeley.com/research/hiv-treatment-prevention-debate-commentarywill-early-infection-compromise-treatmentasprevention-stra", "reader_count"=>73, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>9, "Researcher"=>19, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>2, "Student > Master"=>10, "Other"=>3, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>6}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>9, "Researcher"=>19, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>2, "Student > Master"=>10, "Other"=>3, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>9, "Environmental Science"=>2, "Nursing and Health Professions"=>4, "Materials Science"=>1, "Mathematics"=>3, "Medicine and Dentistry"=>30, "Agricultural and Biological Sciences"=>10, "Business, Management and Accounting"=>3, "Physics and Astronomy"=>1, "Chemistry"=>1, "Social Sciences"=>8, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>30}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>8}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>4}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>3}, "Mathematics"=>{"Mathematics"=>3}, "Unspecified"=>{"Unspecified"=>9}, "Environmental Science"=>{"Environmental Science"=>2}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>3, "Nigeria"=>1, "Switzerland"=>1}, "group_count"=>6}

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• http://doi.org/10.1097/QAD.0000000000001634
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• {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosmedicine%2Farticle%3Fid%3D10.1371%252Fjournal.pmed.1001232", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

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• {"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/25ee5d28-4e2e-4c1f-95f4-bcab45b18958", "title"=>"Response to “HIV Treatment as Prevention: Debate and Commentary-Will Early Infection Compromise Treatment-as-Prevention Strategies?”", "body"=>"Ronald H. Gray, Mary K. Grabowski, Maria J. Wawer\n\nIn the HIV as Prevention Debate, 1 Powers, Miller and Cohen commented that the elevation in transmissibility observed during EHI (early HIV infection) is greater than would be expected based on viral load alone”, and concluded that the mechanism for this “has not been elucidated.” There are a number of reasons why transmission during EHI might be higher than expected compared to the observed rates at similar viral load levels in latent or late infection. There is evidence that only selected transmissible founder viruses which can penetrate the mucosal “bottleneck” are involved in initial heterosexual infection.2,3 The viremia following acute infection is more likely to be dominated by these transmissible founder strains, whereas during latent or late infection, when the viral swarm has diversified under immune pressure, the transmissible viruses are likely to be a minor subset of the total viremia. Thus, the risk of transmission per log increment in viral load would likely diminish during latent stage disease. A meta-analysis by Powers et al. found higher transmission during early compared to later stage disease.4 As noted by Fraser, only the Rakai data provide empirical estimates of transmission from EHI and “is still the best evidence to date on this topic”.1\n\nAnother consideration is the role of genital ulcer disease (GUD) during seroconversion illness which causes a breach of the mucosa and increased genital shedding of virus.5 Rakai data showed that the probability of transmission was increased in the presence of GUD in the HIV-infected partner (0.0041 per coital act with GUD compared to 0.0011 per coital act in the absence of GUD), irrespective of viral load.6 Powers et al., also reported increased infectivity in the presence of GUD.4 In Rakai, the prevalence of GUD during the period concurrent with or immediately after seroconversion was 17.3%, and declined to 11.5% ten or more months after seroconversion: a similar pattern was seen in both HSV-2 infected and uninfected seroconverters.7 Additionally, GUD was associated with upregulation of plasma HIV viral load following seroconversion (p=0.01).8 Thus, it is plausible that GUD amplifies HIV infectivity in EHI due to increased genital shedding, the higher prevalence of ulceration and concomitant upregulation of HIV plasma viral load. In other words, GUD acts as an effect modifier. \n\nIf these arguments are correct, then the assumptions underlying the model by Williams and Dye fail to capture the effects of transmissible virus and GUD in EHI, since they use estimates of the relationship between viral load and HIV transmission derived largely from discordant couples in which the HIV infected partner was in latent stage disease.1 One cannot assume that the relationship between viremia and infectivity in such a population holds for EHI. This suggests that Williams and Dye’s model may underestimate the contributions of EHI to the HIV epidemic and, as a consequence, may also underestimate the potential for EHI to dilute the impact of treatment-as-prevention programs. \n\nReferences\n\n1.\tCohen MS, Dye C, Fraser C, Miller WC, Powers KA, Williams BG. HIV treatment as prevention: debate and commentary--will early infection compromise treatment-as-prevention strategies? PLoS medicine 2012;9:e1001232.\n2.\tKeele BF, Giorgi EE, Salazar-Gonzalez JF, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proceedings of the National Academy of Sciences of the United States of America 2008;105:7552-7.\n3.\tRedd AD, Collinson-Streng AN, Chatziandreou N, et al. Previously transmitted HIV-1 strains are preferentially selected during subsequent sexual transmissions. J Infect Dis 2012;206:1433-42.\n4.\tPowers KA, Poole C, Pettifor AE, Cohen MS. Rethinking the heterosexual infectivity of HIV-1: a systematic review and meta-analysis. Lancet Infect Dis 2008;8:553-63.\n5.\tJohnson LF, Lewis DA. The effect of genital tract infections on HIV-1 shedding in the genital tract: a systematic review and meta-analysis. Sex Transm Dis 2008;35:946-59.\n6.\tGray RH, Wawer MJ, Brookmeyer R, et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 2001;357:1149-53.\n7.\tSerwadda D, Gray RH, Sewankambo NK, et al. Human immunodeficiency virus acquisition associated with genital ulcer disease and herpes simplex virus type 2 infection: a nested case-control study in Rakai, Uganda. J Infect Dis 2003;188:1492-7.\n8.\tGray RH, Li X, Wawer MJ, et al. Determinants of HIV-1 load in subjects with early and later HIV infections, in a general-population cohort of Rakai, Uganda. J Infect Dis 2004;189:1209-15.\n\n", "isRemoved"=>false, "created"=>"2013-01-22T02:46:06Z", "lastModified"=>"2013-01-22T02:46:06Z", "creator"=>{"userId"=>"302909"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>true, "hasCompetingInterests"=>false}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pmed.1001232", "state"=>"published", "journals"=>{"PLoSMedicine"=>{"journalKey"=>"PLoSMedicine", "eIssn"=>"1549-1676", "title"=>"PLOS Medicine"}}}, "replyTreeSize"=>0, "mostRecentActivity"=>"2013-01-22T02:46:06Z", "replies"=>[]}

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• {"month"=>"2", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"24"}
• {"month"=>"3", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"34"}
• {"month"=>"4", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"60"}
• {"month"=>"5", "year"=>"2016", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"45"}
• {"month"=>"6", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"43"}
• {"month"=>"7", "year"=>"2016", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"56"}
• {"month"=>"8", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"71"}
• {"month"=>"9", "year"=>"2016", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"58"}
• {"month"=>"10", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"65"}
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• {"month"=>"12", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"43"}
• {"month"=>"1", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"59"}
• {"month"=>"2", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"62"}
• {"month"=>"3", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"61"}
• {"month"=>"4", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"74"}
• {"month"=>"5", "year"=>"2017", "pdf_views"=>"10", "xml_views"=>"2", "html_views"=>"48"}
• {"month"=>"6", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"48"}
• {"month"=>"7", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"62"}
• {"month"=>"8", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"3", "html_views"=>"36"}
• {"month"=>"9", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"31"}
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• {"month"=>"7", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"13"}
• {"month"=>"8", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"16"}
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• {"month"=>"11", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"18"}
• {"month"=>"12", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"6"}
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• {"month"=>"2", "year"=>"2020", "pdf_views"=>"5", "xml_views"=>"1", "html_views"=>"3"}
• {"month"=>"3", "year"=>"2020", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"6"}
• {"month"=>"4", "year"=>"2020", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"3"}
• {"month"=>"5", "year"=>"2020", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"3"}
• {"month"=>"6", "year"=>"2020", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"13"}
• {"month"=>"7", "year"=>"2020", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"6"}
• {"month"=>"8", "year"=>"2020", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"10"}
• {"month"=>"9", "year"=>"2020", "pdf_views"=>"24", "xml_views"=>"0", "html_views"=>"8"}
• {"month"=>"10", "year"=>"2020", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"5"}
• {"month"=>"11", "year"=>"2020", "pdf_views"=>"18", "xml_views"=>"1", "html_views"=>"14"}
• {"month"=>"12", "year"=>"2020", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"8"}
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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/612837"], "description"=>"<p>(A) Green line: prevalence; red line: incidence. Two versions of a model are fitted to the adult HIV prevalence curve for South Africa (Joint United Nations Programme on HIV/AIDS): one “corrected” for serial monogamy effects in low-risk individuals <a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001232#pmed.1001232-Cohen1\" target=\"_blank\">[5]</a>, and thus with a low contribution of AHI (solid line), and one without the correction, and thus with a high contribution of AHI (dashed line). Fitted parameters are as follows: the proportion of individuals in three risk groups (low, medium, and high), rate of partner change for high-risk individuals, assortativity of mixing by risk, start time, early treatment rates, and an overall infectiousness parameter. Other parameters were fixed from the literature <a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001232#pmed.1001232-Cohen3\" target=\"_blank\">[13]</a>,<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001232#pmed.1001232-Gardner1\" target=\"_blank\">[14]</a>. (C) The intervention is introduced in 2012, and predictions are made until 2020, for three scenarios ranging from the very pessimistic (green line), through “just on target” (red line), to very optimistic (blue line). The results are surprisingly independent of the amount of transmission from AHI, as indicated by the solid versus dashed lines. (B and D) The contribution to transmission from individuals in different disease stages in the just-on-target scenarios is plotted in (B), corresponding to solid lines in (A) and (C) (corrected for serial monogamy effects), and (D), corresponding to dashed lines in (A) and (C) (not corrected for serial monogamy effects). Shown are all new infections of index cases in AHI and EHI (green), of index cases in untreated CHI (blue), and of index cases in treated CHI (red), as a proportion of total new infections.</p>", "links"=>[], "tags"=>["levels", "acute", "tested", "popart"], "article_id"=>283328, "categories"=>["Medicine"], "users"=>["Myron S. Cohen", "Christopher Dye", "Christophe Fraser", "William C. Miller", "Kimberly A. Powers", "Brian G. Williams"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001232.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_predicted_effect_of_different_levels_of_acute_infection_on_a_combination_prevention_package_including_universal_testing_and_treatment_as_will_be_tested_in_the_PopART_trial_20_/283328", "title"=>"The predicted effect of different levels of acute infection on a combination prevention package including universal testing and treatment, as will be tested in the PopART trial [20].", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 02:50:39"}

PMC Usage Stats | Further Information

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• {"unique-ip"=>"14", "full-text"=>"20", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
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• {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
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• {"unique-ip"=>"11", "full-text"=>"16", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
• {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
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Relative Metric

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F1000Prime