Limited Durability of Viral Control following Treated Acute HIV Infection
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{"title"=>"Limited durability of viral control following treated acute HIV infection", "type"=>"journal", "authors"=>[{"first_name"=>"Daniel E.", "last_name"=>"Kaufmann", "scopus_author_id"=>"7006478468"}, {"first_name"=>"Mathias", "last_name"=>"Lichterfeld", "scopus_author_id"=>"6602189737"}, {"first_name"=>"Marcus", "last_name"=>"Altfeld", "scopus_author_id"=>"7003649192"}, {"first_name"=>"Marylyn M.", "last_name"=>"Addo", "scopus_author_id"=>"7003849590"}, {"first_name"=>"Mary N.", "last_name"=>"Johnston", "scopus_author_id"=>"7402060754"}, {"first_name"=>"Paul K.", "last_name"=>"Lee", "scopus_author_id"=>"7406118306"}, {"first_name"=>"Bradford S.", "last_name"=>"Wagner", "scopus_author_id"=>"57196647191"}, {"first_name"=>"Elizabeth T.", "last_name"=>"Kalife", "scopus_author_id"=>"8957780200"}, {"first_name"=>"Daryld", "last_name"=>"Strick", "scopus_author_id"=>"6603302939"}, {"first_name"=>"Eric S.", "last_name"=>"Rosenberg", "scopus_author_id"=>"7201542394"}, {"first_name"=>"Bruce D.", "last_name"=>"Walker", "scopus_author_id"=>"7402209193"}], "year"=>2004, "source"=>"PLoS Medicine", "identifiers"=>{"issn"=>"15491277", "pmid"=>"15526059", "pui"=>"40412717", "scopus"=>"2-s2.0-15744361847", "doi"=>"10.1371/journal.pmed.0010036", "isbn"=>"1549-1676 (Electronic)\\r1549-1277 (Linking)", "sgr"=>"15744361847"}, "id"=>"f2a144fe-e4ea-38df-a901-c0eab0971dd3", "abstract"=>"BACKGROUND: Early treatment of acute HIV infection with highly active antiretroviral therapy, followed by supervised treatment interruption (STI), has been associated with at least transient control of viremia. However, the durability of such control remains unclear. Here we present longitudinal follow-up of a single-arm, open-label study assessing the impact of STI in the setting of acute HIV-1 infection.\\n\\nMETHODS AND FINDINGS: Fourteen patients were treated during acute HIV-1 infection and subsequently subjected to an STI protocol that required retreatment if viral load exceeded 50,000 RNA copies/ml plasma or remained above 5,000 copies/ml for more than three consecutive weeks. Eleven of 14 (79%) patients were able to achieve viral loads of less than 5,000 RNA copies/ml for at least 90 d following one, two, or three interruptions of treatment. However, a gradual increase in viremia and decline in CD4+ T cell counts was observed in most individuals. By an intention-to-treat analysis, eight (57%), six (43%), and three (21%) of 14 patients achieved a maximal period of control of 180, 360, and 720 d, respectively, despite augmentation of HIV-specific CD4+ and CD8+ T cell responses. The magnitude of HIV-1-specific cellular immune responses before treatment interruption did not predict duration of viremia control. The small sample size and lack of concurrent untreated controls preclude assessment of possible clinical benefit despite failure to control viremia by study criteria.\\n\\nCONCLUSIONS: These data indicate that despite initial control of viremia, durable viral control to less than 5,000 RNA copies/ml plasma in patients following treated acute HIV-1 infection occurs infrequently. Determination of whether early treatment leads to overall clinical benefit will require a larger and randomized clinical trial. These data may be relevant to current efforts to develop an HIV-1 vaccine designed to retard disease progression rather than prevent infection since they indicate that durable maintenance of low-level viremia may be difficult to achieve.", "link"=>"http://www.mendeley.com/research/limited-durability-viral-control-following-treated-acute-hiv-infection", "reader_count"=>54, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>6, "Librarian"=>1, "Researcher"=>13, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>6, "Other"=>4, "Student > Master"=>4, "Student > Bachelor"=>2, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>6, "Librarian"=>1, "Researcher"=>13, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>6, "Other"=>4, "Student > Master"=>4, "Student > Bachelor"=>2, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Medicine and Dentistry"=>25, "Agricultural and Biological Sciences"=>16, "Psychology"=>1, "Social Sciences"=>3, "Computer Science"=>1, "Immunology and Microbiology"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>25}, "Social Sciences"=>{"Social Sciences"=>3}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Computer Science"=>{"Computer Science"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Belgium"=>1, "United States"=>2}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/473521", "https://ndownloader.figshare.com/files/473553", "https://ndownloader.figshare.com/files/473565", "https://ndownloader.figshare.com/files/473681"], "description"=>"<div><h3>Background</h3><p>Early treatment of acute HIV infection with highly active antiretroviral therapy, followed by supervised treatment interruption (STI), has been associated with at least transient control of viremia. However, the durability of such control remains unclear. Here we present longitudinal follow-up of a single-arm, open-label study assessing the impact of STI in the setting of acute HIV-1 infection.</p> <h3>Methods and Findings</h3><p>Fourteen patients were treated during acute HIV-1 infection and subsequently subjected to an STI protocol that required retreatment if viral load exceeded 50,000 RNA copies/ml plasma or remained above 5,000 copies/ml for more than three consecutive weeks. Eleven of 14 (79%) patients were able to achieve viral loads of less than 5,000 RNA copies/ml for at least 90 d following one, two, or three interruptions of treatment. However, a gradual increase in viremia and decline in CD4+ T cell counts was observed in most individuals. By an intention-to-treat analysis, eight (57%), six (43%), and three (21%) of 14 patients achieved a maximal period of control of 180, 360, and 720 d, respectively, despite augmentation of HIV-specific CD4+ and CD8+ T cell responses. The magnitude of HIV-1-specific cellular immune responses before treatment interruption did not predict duration of viremia control. The small sample size and lack of concurrent untreated controls preclude assessment of possible clinical benefit despite failure to control viremia by study criteria.</p> <h3>Conclusions</h3><p>These data indicate that despite initial control of viremia, durable viral control to less than 5,000 RNA copies/ml plasma in patients following treated acute HIV-1 infection occurs infrequently. Determination of whether early treatment leads to overall clinical benefit will require a larger and randomized clinical trial. These data may be relevant to current efforts to develop an HIV-1 vaccine designed to retard disease progression rather than prevent infection since they indicate that durable maintenance of low-level viremia may be difficult to achieve.</p> </div>", "links"=>[], "tags"=>["durability", "viral", "treated", "acute", "hiv"], "article_id"=>153305, "categories"=>["Cancer", "Medicine", "Immunology"], "users"=>["Daniel E Kaufmann", "Mathias Lichterfeld", "Marcus Altfeld", "Marylyn M Addo", "Mary N Johnston", "Paul K Lee", "Bradford S Wagner", "Elizabeth T Kalife", "Daryld Strick", "Eric S Rosenberg", "Bruce D Walker"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.0010036.sd001", "https://dx.doi.org/10.1371/journal.pmed.0010036.sd002", "https://dx.doi.org/10.1371/journal.pmed.0010036.sd003", "https://dx.doi.org/10.1371/journal.pmed.0010036.sd004"], "stats"=>{"downloads"=>60, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Limited_Durability_of_Viral_Control_following_Treated_Acute_HIV_Infection/153305", "title"=>"Limited Durability of Viral Control following Treated Acute HIV Infection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-01-20 11:36:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/963549"], "description"=>"<div><p>(A) Survival curves of time to virologic failure during the first three supervised treatment interruptions. Virologic failure was defined as having a viral load of greater than 5,000 copies RNA/ml plasma for 3 wk or greater than 50,000 copies once. Patients still achieving viral control at the last visit and individuals restarting therapy without meeting criteria or lost in follow-up are censored at the last evaluable time point. The horizontal axis represents the time off therapy since the beginning of the treatment interruption, the vertical axis corresponds to the number of patients maintaining control of viremia. The curves for first, second, and third STIs do not differ significantly from each other (log-rank test, <i>p ></i> 0.05).</p>\n <p>(B) Evolution of CD4+ T cell counts during the longest treatment interruption. Slopes of CD4+ T cell counts during the first year of the longest treatment interruption are shown for patients who experienced a cessation of therapy of at least 12 mo (all except AC13, AC25, and AC45), compared to the natural decline of CD4+ T cell counts in untreated patients of the MACS cohort with early chronic HIV-1 infection (CD4+ counts of >350 cells/mm<sup>3</sup>). CD4+ T cell losses were calculated on a regression line based on least squares fit. The two groups differed significantly from each other (Mann-Whitney <i>U</i> test, <i>p =</i> 0.02).</p>\n <p>(C) CD4+ T cell count at intercept and CD4+ T cell slopes during the longest treatment interruption. The CD4+ T cell slopes of the same 11 patients shown in (B) and of untreated patients of the MACS cohort are represented according to the CD4+ T cell count at the intercept of the regression line based on least squares fit with the vertical axis (day 0 of treatment interruption).</p></div>", "links"=>[], "tags"=>["viral", "counts"], "article_id"=>633490, "categories"=>["Medicine", "Infectious Diseases", "Immunology"], "users"=>["Daniel E Kaufmann", "Mathias Lichterfeld", "Marcus Altfeld", "Marylyn M Addo", "Mary N Johnston", "Paul K Lee", "Bradford S Wagner", "Elizabeth T Kalife", "Daryld Strick", "Eric S Rosenberg", "Bruce D Walker"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0010036.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evolution_of_Viral_Load_and_CD4_T_Cell_Counts_during_STI_/633490", "title"=>"Evolution of Viral Load and CD4+ T Cell Counts during STI", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 09:12:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/963400"], "description"=>"<p>Time zero corresponds to first institution of highly active antiretroviral therapy (HAART). Closed squares, HIV-1 plasma viral loads; open circles, CD4+ T cell counts; shaded areas, treatment with HAART according to protocol; diagonally shaded areas, patient restarted therapy without meeting criteria of virological failure; vertical dotted lines, virological failure without reinstitution of HAART. Patients are ordered by increasing number of supervised treatment interruptions.</p>", "links"=>[], "tags"=>["viral", "loads", "counts", "14"], "article_id"=>633332, "categories"=>["Medicine", "Infectious Diseases", "Immunology"], "users"=>["Daniel E Kaufmann", "Mathias Lichterfeld", "Marcus Altfeld", "Marylyn M Addo", "Mary N Johnston", "Paul K Lee", "Bradford S Wagner", "Elizabeth T Kalife", "Daryld Strick", "Eric S Rosenberg", "Bruce D Walker"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0010036.g001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HIV_1_Viral_Loads_and_CD4_T_Cell_Counts_in_the_14_Study_Participants_/633332", "title"=>"HIV-1 Viral Loads and CD4+ T Cell Counts in the 14 Study Participants", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 09:10:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/963670"], "description"=>"<div><p>(A–D) Magnitude and breadth of increase of HIV-specific CD8+ T cells during supervised treatment interruptions.</p>\n <p>(A and B) Magnitude (A) and breadth (B) of HIV-specific CD8+ responses at the first day of treatment interruption (black bars) and at the last day off therapy (white bars). Data represent the mean and standard deviation.</p>\n <p>(C and D) Correlation between the increase of the magnitude (C) or breadth (D) of CD8+ T cell responses and the time off therapy during the first treatment interruption.</p>\n <p>(E and F) Evolution of CD4+ T helper cell responses during supervised treatment interruptions.</p>\n <p>(E) Magnitude of CD4 T helper cell responses at baseline and at the first day of treatment interruption (closed circles) and last day off therapy (open circles). Horizontal bars correspond to median values. An stimulation index greater than five was considered significant.</p>\n <p>(F) Correlation between the magnitude of p24-specific lymphocyte proliferative responses at the beginning of the first treatment interruption and the time patients were able to remain off therapy during the subsequent STI.</p></div>", "links"=>[], "tags"=>["hiv-1-specific", "responses"], "article_id"=>633605, "categories"=>["Medicine", "Infectious Diseases", "Immunology"], "users"=>["Daniel E Kaufmann", "Mathias Lichterfeld", "Marcus Altfeld", "Marylyn M Addo", "Mary N Johnston", "Paul K Lee", "Bradford S Wagner", "Elizabeth T Kalife", "Daryld Strick", "Eric S Rosenberg", "Bruce D Walker"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0010036.g003", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evolution_of_HIV_1_Specific_CD4_and_CD8_T_Cell_Responses_during_STI_/633605", "title"=>"Evolution of HIV-1-Specific CD4+ and CD8+ T Cell Responses during STI", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 09:12:48"}

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