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{"title"=>"Cd4 cell count and the risk of AIDS or death in HIV-infected adults on combination antiretroviral therapy with a suppressed viral load: A longitudinal cohort study from COHERE", "type"=>"journal", "authors"=>[{"last_name"=>"Young", "scopus_author_id"=>"55251021100"}], "year"=>2012, "source"=>"PLoS Medicine", "identifiers"=>{"doi"=>"10.1371/journal.pmed.1001194", "sgr"=>"84862215127", "issn"=>"15491676", "pui"=>"364985888", "isbn"=>"1549-1676 (Electronic)\\n1549-1277 (Linking)", "pmid"=>"22448150", "scopus"=>"2-s2.0-84862215127"}, "id"=>"98eebd27-3f9c-3d1e-a148-96baae758951", "abstract"=>"BACKGROUND: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.\\n\\nMETHODS AND FINDINGS: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements <50 copies/µl and ending with either a measurement >500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30-0.40) for counts <200 cells/µl, 0.81 (0.71-0.92) for counts 200 to <350 cells/µl, 0.74 (0.66-0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl.\\n\\nCONCLUSIONS: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.", "link"=>"http://www.mendeley.com/research/cd4-cell-count-risk-aids-death-hivinfected-adults-combination-antiretroviral-therapy-suppressed-vira", "reader_count"=>113, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>34, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>22, "Student > Postgraduate"=>11, "Student > Master"=>16, "Other"=>7, "Student > Bachelor"=>4, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>34, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>22, "Student > Postgraduate"=>11, "Student > Master"=>16, "Other"=>7, "Student > Bachelor"=>4, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>11, "Biochemistry, Genetics and Molecular Biology"=>6, "Nursing and Health Professions"=>4, "Mathematics"=>1, "Medicine and Dentistry"=>61, "Agricultural and Biological Sciences"=>11, "Sports and Recreations"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Social Sciences"=>6, "Immunology and Microbiology"=>9, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>61}, "Social Sciences"=>{"Social Sciences"=>6}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>9}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>11}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Ecuador"=>1, "United States"=>4, "Tanzania"=>1, "Brazil"=>3, "Zimbabwe"=>1, "Switzerland"=>1, "Spain"=>1, "India"=>1}, "group_count"=>4}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/664809"], "description"=>"<p>Event rates in CD4 strata among the 75,336 patients with at least one suppression episode while on cART: event rates per 1,000 y of suppressed viral load (number of events) over time for the primary outcome (a first new AIDS event or death).</p>", "links"=>[], "tags"=>["rates", "cd4", "strata", "patients", "suppression", "suppressed", "viral", "aids"], "article_id"=>335301, "categories"=>["Infectious Diseases"], "users"=>["The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001194.t004", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Event_rates_in_CD4_strata_among_the_75_336_patients_with_at_least_one_suppression_episode_while_on_cART_event_rates_per_1_000_y_of_suppressed_viral_load_number_of_events_over_time_for_the_primary_outcome_a_first_new_AIDS_event_or_death_/335301", "title"=>"Event rates in CD4 strata among the 75,336 patients with at least one suppression episode while on cART: event rates per 1,000 y of suppressed viral load (number of events) over time for the primary outcome (a first new AIDS event or death).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-20 01:28:21"}
• {"files"=>["https://ndownloader.figshare.com/files/664717"], "description"=>"<p>Event rates in CD4 strata among the 75,336 patients with at least one suppression episode while on cART: event rates per 1,000 y of suppressed viral load (number of events) by outcome.</p>", "links"=>[], "tags"=>["rates", "cd4", "strata", "patients", "suppression", "suppressed", "viral"], "article_id"=>335206, "categories"=>["Infectious Diseases"], "users"=>["The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001194.t002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Event_rates_in_CD4_strata_among_the_75_336_patients_with_at_least_one_suppression_episode_while_on_cART_event_rates_per_1_000_y_of_suppressed_viral_load_number_of_events_by_outcome_/335206", "title"=>"Event rates in CD4 strata among the 75,336 patients with at least one suppression episode while on cART: event rates per 1,000 y of suppressed viral load (number of events) by outcome.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-20 01:26:46"}
• {"files"=>["https://ndownloader.figshare.com/files/664755"], "description"=>"<p>Four first new AIDS events could not be classified as either an opportunistic infection or an HIV-related neoplasm.</p>", "links"=>[], "tags"=>["rates", "cd4", "strata", "patients", "suppression", "suppressed", "viral", "aids", "classified", "opportunistic", "hiv"], "article_id"=>335238, "categories"=>["Infectious Diseases"], "users"=>["The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001194.t003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Event_rates_in_CD4_strata_among_the_75_336_patients_with_at_least_one_suppression_episode_while_on_cART_event_rates_per_1_000_y_of_suppressed_viral_load_number_of_events_for_a_first_new_AIDS_event_with_each_event_then_classified_as_either_an_opportunisti/335238", "title"=>"Event rates in CD4 strata among the 75,336 patients with at least one suppression episode while on cART: event rates per 1,000 y of suppressed viral load (number of events) for a first new AIDS event, with each event then classified as either an opportunistic infection or a HIV related neoplasm.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-20 01:27:18"}
• {"files"=>["https://ndownloader.figshare.com/files/341178"], "description"=>"<div><h3>Background</h3><p>Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.</p> <h3>Methods and Findings</h3><p>Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements <50 copies/µl and ending with either a measurement >500 copies/µl, the first of two consecutive measurements between 50–500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30–0.40) for counts <200 cells/µl, 0.81 (0.71–0.92) for counts 200 to <350 cells/µl, 0.74 (0.66–0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92–0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl.</p> <h3>Conclusions</h3><p>Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.</p> <h3></h3><p> <em>Please see later in the article for the Editors' Summary</em></p> </div>", "links"=>[], "tags"=>["cd4", "aids", "hiv-infected", "adults", "antiretroviral", "suppressed", "viral", "longitudinal", "cohort", "cohere"], "article_id"=>127445, "categories"=>["Cancer"], "users"=>["The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001194", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/CD4_Cell_Count_and_the_Risk_of_AIDS_or_Death_in_HIV_Infected_Adults_on_Combination_Antiretroviral_Therapy_with_a_Suppressed_Viral_Load_A_Longitudinal_Cohort_Study_from_COHERE/127445", "title"=>"CD4 Cell Count and the Risk of AIDS or Death in HIV-Infected Adults on Combination Antiretroviral Therapy with a Suppressed Viral Load: A Longitudinal Cohort Study from COHERE", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-20 02:04:05"}
• {"files"=>["https://ndownloader.figshare.com/files/664780"], "description"=>"<p>Note that the number of patients included in the main analyses of primary and secondary outcomes (<i>n</i> = 66,147) is lower than the number of patients in <a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001194#pmed-1001194-t002\" target=\"_blank\">Tables 2</a>–<a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001194#pmed-1001194-t003\" target=\"_blank\"></a><a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001194#pmed-1001194-t004\" target=\"_blank\">4</a> with at least one suppression episode (<i>n</i> = 75,336) because viral load prior to starting cART was not known for some patients.</p>a<p>Nationality was not recorded for 40% of patients included in these analyses and for 50% of patients excluded from these analyses.</p>b<p>At the start of a first suppression episode. Note that 103 patients that did not contribute a first episode to the main analyses because either no CD4 cell counts were available for this episode or this episode occurred while the patient was still under the age of 16.</p>c<p>Last viral load before starting combination therapy. Note that a further 4,211 patients did not contribute a first episode to the main analyses because their viral load before starting combination therapy was not known (although these patients contributed a first episode to the sensitivity analysis without this covariate).</p>d<p>Other: at least one protease inhibitor (PI) and one non-nucleoside reverse-transcriptase inhibitor (NNRTI), 5%; three NRTIs, 3%; at least two PIs (other than ritonavir) but no NNRTI, 2%; any therapy including integrase or fusion inhibitors, 1%.</p>", "links"=>[], "tags"=>["patients", "episodic", "viral", "suppression"], "article_id"=>335275, "categories"=>["Infectious Diseases"], "users"=>["The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001194.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_COHERE_patients_with_continuous_or_episodic_viral_suppression_while_on_cART_/335275", "title"=>"COHERE patients with continuous or episodic viral suppression while on cART.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-20 01:27:55"}
• {"files"=>["https://ndownloader.figshare.com/files/664587"], "description"=>"<p>These plots apply to hypothetical patients whose CD4 cell count remains within the same CD4 stratum while on cART with a suppressed viral load. Plot (A) shows a Kaplan Meier plot of the probability of AIDS event-free survival over time. Plot (B) shows a plot of log(−log [probability of AIDS event-free survival]) against log(time). The roughly parallel lines of plot (B) suggest that a proportional hazards model is appropriate for these data. Both plots use a method appropriate for a time-dependent CD4 cell count (see <a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001194#pmed.1001194-Snapinn1\" target=\"_blank\">[16]</a>).</p>", "links"=>[], "tags"=>["plots", "aids", "event-free"], "article_id"=>335085, "categories"=>["Infectious Diseases"], "users"=>["The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001194.g001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Probability_plots_of_AIDS_event_free_survival_over_time_/335085", "title"=>"Probability plots of AIDS event-free survival over time.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-20 01:24:45"}
• {"files"=>["https://ndownloader.figshare.com/files/664856"], "description"=>"a<p>Time-dependent covariate.</p>b<p>Last viral load prior to starting cART or highest viral load recorded between episodes.</p>c<p>Other: at least one protease inhibitor (PI) and one non-nucleoside reverse-transcriptase inhibitor (NNRTI), at least two PIs (other than ritonavir) but no NNRTI; any therapy including integrase or fusion inhibitors.</p>d<p>Time-dependent covariate. A HR<1.0 for any of the four components of this spline implies that a higher CD4 cell count (per 100 cells/µl) is associated with a lower risk of progression and is therefore a measure of the benefit that a patient can expect if their CD4 cell count increases above any current level within the range covered by that spline component.</p>", "links"=>[], "tags"=>["estimates", "cis", "multivariate", "cox", "proportional", "models", "patients", "suppressed", "viral"], "article_id"=>335343, "categories"=>["Infectious Diseases"], "users"=>["The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001194.t005", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HR_estimates_and_their_95_CIs_from_multivariate_Cox_proportional_hazard_models_for_both_the_primary_and_secondary_outcome_in_66_147_patients_on_cART_with_a_suppressed_viral_load_/335343", "title"=>"HR estimates and their 95% CIs from multivariate Cox proportional hazard models for both the primary and secondary outcome in 66,147 patients on cART with a suppressed viral load.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-20 01:29:03"}

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F1000Prime