HIV-1 Transmission during Early Antiretroviral Therapy: Evaluation of Two HIV-1 Transmission Events in the HPTN 052 Prevention Study
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{"title"=>"HIV-1 Transmission during Early Antiretroviral Therapy: Evaluation of Two HIV-1 Transmission Events in the HPTN 052 Prevention Study", "type"=>"journal", "authors"=>[{"first_name"=>"Li Hua", "last_name"=>"Ping", "scopus_author_id"=>"7102920499"}, {"first_name"=>"Cassandra B.", "last_name"=>"Jabara", "scopus_author_id"=>"8285222400"}, {"first_name"=>"Allen G.", "last_name"=>"Rodrigo", "scopus_author_id"=>"7005923028"}, {"first_name"=>"Sarah E.", "last_name"=>"Hudelson", "scopus_author_id"=>"9333527800"}, {"first_name"=>"Estelle", "last_name"=>"Piwowar-Manning", "scopus_author_id"=>"35783326900"}, {"first_name"=>"Lei", "last_name"=>"Wang", "scopus_author_id"=>"57070557000"}, {"first_name"=>"Susan H.", "last_name"=>"Eshleman", "scopus_author_id"=>"7004740977"}, {"first_name"=>"Myron S.", "last_name"=>"Cohen", "scopus_author_id"=>"54790532400"}, {"first_name"=>"Ronald", "last_name"=>"Swanstrom", "scopus_author_id"=>"7004358853"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"24086252", "sgr"=>"84884541971", "scopus"=>"2-s2.0-84884541971", "doi"=>"10.1371/journal.pone.0071557", "pui"=>"369882576", "issn"=>"19326203"}, "id"=>"b04b3470-ba82-3e2a-8e9e-6bc8ddcfd6e8", "abstract"=>"In the HPTN 052 study, transmission between HIV-discordant couples was reduced by 96% when the HIV-infected partner received suppressive antiretroviral therapy (ART). We examined two transmission events where the newly infected partner was diagnosed after the HIV-infected partner (index) initiated therapy. We evaluated the sequence complexity of the viral populations and antibody reactivity in the newly infected partner to estimate the dates of transmission to the newly infected partners. In both cases, transmission most likely occurred significantly before HIV-1 diagnosis of the newly infected partner, and either just before the initiation of therapy or before viral replication was adequately suppressed by therapy of the index. This study further strengthens the conclusion about the efficacy of blocking transmission by treating the infected partner of discordant couples. However, this study does not rule out the potential for HIV-1 transmission to occur shortly after initiation of ART, and this should be recognized when antiretroviral therapy is used for HIV-1 prevention.", "link"=>"http://www.mendeley.com/research/hiv1-transmission-during-early-antiretroviral-therapy-evaluation-two-hiv1-transmission-events-hptn-0", "reader_count"=>17, "reader_count_by_academic_status"=>{"Researcher"=>5, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>4, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Researcher"=>5, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>4, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Mathematics"=>1, "Medicine and Dentistry"=>7, "Agricultural and Biological Sciences"=>4, "Business, Management and Accounting"=>1, "Social Sciences"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1214917"], "description"=>"<div><p>In the HPTN 052 study, transmission between HIV-discordant couples was reduced by 96% when the HIV-infected partner received suppressive antiretroviral therapy (ART). We examined two transmission events where the newly infected partner was diagnosed after the HIV-infected partner (index) initiated therapy. We evaluated the sequence complexity of the viral populations and antibody reactivity in the newly infected partner to estimate the dates of transmission to the newly infected partners. In both cases, transmission most likely occurred significantly before HIV-1 diagnosis of the newly infected partner, and either just before the initiation of therapy or before viral replication was adequately suppressed by therapy of the index. This study further strengthens the conclusion about the efficacy of blocking transmission by treating the infected partner of discordant couples. However, this study does not rule out the potential for HIV-1 transmission to occur shortly after initiation of ART, and this should be recognized when antiretroviral therapy is used for HIV-1 prevention.</p></div>", "links"=>[], "tags"=>["antiretroviral", "hiv-1", "hptn", "052"], "article_id"=>807573, "categories"=>["Biological Sciences"], "users"=>["Li-Hua Ping", "Cassandra B. Jabara", "Allen G. Rodrigo", "Sarah E. Hudelson", "Estelle Piwowar-Manning", "Lei Wang", "Susan H. Eshleman", "Myron S. Cohen", "Ronald Swanstrom"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071557", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HIV_1_Transmission_during_Early_Antiretroviral_Therapy_Evaluation_of_Two_HIV_1_Transmission_Events_in_the_HPTN_052_Prevention_Study_/807573", "title"=>"HIV-1 Transmission during Early Antiretroviral Therapy: Evaluation of Two HIV-1 Transmission Events in the HPTN 052 Prevention Study", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-09-24 02:21:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1214915"], "description"=>"<p>The program BEAST was used to recreate phylogeny (Bayesian skyline) of the viral <i>env</i> sequences generated from the index (black) and partner (red) for Case A (Panel A) and Case B (Panel B). Each tip (with dot) of the tree is an individual sequence. For Case A, sequences from the partner are dispersed among the sequences from the index, indicating the transmission of at least four variants (seen as four discrete positions in the tree where one or more red dots occur). For Case B, the sequences from the partner represent a single lineage/cluster, indicative of transmission of a single variant. The tree structure moves back in time from right to left as indicated by the arrow at the bottom and with the scale shown for 100 days. The tips of the tree are displaced to correspond to the date the sample was taken that gave rise to those sequences. Each internal node/branch point in the tree represents the inferred most recent common ancestor (MRCA) of all sequences that appear to the right of the node, with the position of each node given an estimated date from the date the partner's infection was detected. The dates (in days) of the MRCA within each partner (interpreted as the date expansion of the virus population started after the transmission event) are indicated (40 days for Case A; 84 days for Case B), and the relevant nodes circled. The numbers in small font indicate the estimated error in the dating of each node. The time to MRCA was estimated from two independent runs which were combined, the HKY substitution model, estimated base frequencies, Gamma site heterogeneity model with 4 gamma categories, a strict clock with a fixed mutation rate of 1.5×10<sup>−5</sup>, partner tip dating, and the Bayesian skyline tree model.</p>", "links"=>[], "tags"=>["viral", "populations"], "article_id"=>807571, "categories"=>["Biological Sciences"], "users"=>["Li-Hua Ping", "Cassandra B. Jabara", "Allen G. Rodrigo", "Sarah E. Hudelson", "Estelle Piwowar-Manning", "Lei Wang", "Susan H. Eshleman", "Myron S. Cohen", "Ronald Swanstrom"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071557.g002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phylogenetic_analysis_of_viral_populations_in_the_index_and_partner_/807571", "title"=>"Phylogenetic analysis of viral populations in the index and partner.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-24 02:21:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1214916"], "description"=>"a<p>HIV-1 diagnosis indicates the number of days between ART initiation in the index and HIV-1 diagnosis in the partner (first HIV-positive sample).</p>b<p>Estimate of the time between HIV-1 transmission and HIV-1 diagnosis in the newly-infected partner based on BEAST analysis.</p>c<p>Estimate of the time between HIV-1 transmission and HIV-1 diagnosis in the newly-infected partner based on use of the Poisson Fitter (Case A only).</p>d<p>The table shows the earliest and average number of days between HIV-1 transmission and the Fiebig stage of each of the newly-infected partners, based on Western blot analysis. The partner in Case A was Fiebig stage V; the partner in Case B was Fiebig Stage VI <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071557#pone.0071557-Fiebig1\" target=\"_blank\">[12]</a>; a 7-day eclipse period was included in the calculations.</p>", "links"=>[], "tags"=>["poisson", "fitter", "serological", "days", "hiv-1", "newly-infected", "initiation"], "article_id"=>807572, "categories"=>["Biological Sciences"], "users"=>["Li-Hua Ping", "Cassandra B. Jabara", "Allen G. Rodrigo", "Sarah E. Hudelson", "Estelle Piwowar-Manning", "Lei Wang", "Susan H. Eshleman", "Myron S. Cohen", "Ronald Swanstrom"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071557.t001", "stats"=>{"downloads"=>0, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Data_obtained_using_BEAST_analysis_the_Poisson_Fitter_tool_and_serological_analysis_are_expressed_as_the_number_of_days_between_the_estimated_date_of_HIV_1_transmission_and_HIV_1_diagnosis_in_the_newly_infected_partner_These_data_are_also_shown_in_Figure/807572", "title"=>"Data obtained using BEAST analysis, the Poisson Fitter tool, and serological analysis are expressed as the number of days between the estimated date of HIV-1 transmission and HIV-1 diagnosis in the newly-infected partner. These data are also shown in Figure 1B, expressed as days before or after ART initiation in the index.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-09-24 02:21:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1214914"], "description"=>"<p>A. A timeline (in days) is shown relative to the date of initiation of therapy (D<sub>0</sub>) for both Case A and Case B. Dates are shown for the proximal time prior to therapy when the viral load in the index was determined along with the proximal date after the initiation of therapy when the index had a viral RNA load below 400 copies/ml. Similarly, the date proximal to but before the date of initiation of therapy when the partner was HIV- (less than 40 copies/ml) and when the partner was diagnosed by western blot analysis (WB) as being HIV+. B. Estimates of the date of transmission to the newly infected partner are shown by the colored horizontal lines on the same timeline as in Panel A, shown separately for Case A and Case B. The gray background indicates the period on therapy for the index. The small black vertical open boxes indicate the dates of the last HIV- sample from each partner, and these boxes are preceded by a black vertical dashed line to indicate the eclipse period (7 days) when transmission could have occurred but not been detected in the blood. The vertical red boxes indicate the dates of the first HIV+ sample in the partners. The horizontal lines represent the range of the possible dates of transmission inferred using the several different approaches. The length of the horizontal line is meant to indicate the uncertainty associated with the estimate. The vertical bar on the horizontal line represents the most likely date of transmission given the sequence diversity. Estimates for the transmission date are shown for serology (in orange), sequence diversity using the Poisson Fitter (in purple), and for expansion of the sequence population in the partner using BEAST (i.e. time to most recent common ancestor/MRCA; in dark blue). For the serology estimate we used the shortest period of time needed for a newly infected person to progress to Fiebig Stage V (23 days) or Fiebig Stage VI) (55 days). Since an infected person can stay in either of these stages for an extended period of time these lines are left-censored at the earliest possible transmission date (dashed black vertical line) given the negative HIV-1 viral RNA load assay plus the eclipse period.</p>", "links"=>[], "tags"=>["estimating", "dates", "initiation"], "article_id"=>807570, "categories"=>["Biological Sciences"], "users"=>["Li-Hua Ping", "Cassandra B. Jabara", "Allen G. Rodrigo", "Sarah E. Hudelson", "Estelle Piwowar-Manning", "Lei Wang", "Susan H. Eshleman", "Myron S. Cohen", "Ronald Swanstrom"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071557.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Timeline_and_summary_of_data_estimating_dates_of_transmission_relative_to_the_initiation_of_therapy_/807570", "title"=>"Timeline and summary of data estimating dates of transmission relative to the initiation of therapy.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-09-24 02:21:33"}

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