Comparison of methods for correction of mortality estimates for loss to follow-up after ART initiation: a case of the Infectious Diseases Institute, Uganda
In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The objective of this study was to validate methods used to correct mortality estimates for loss-to-follow-up using a cohort with complete death ascertainm...
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| Published in | PloS one Vol. 8; no. 12; p. e83524 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
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Public Library of Science
31.12.2013
Public Library of Science (PLoS) |
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| Abstract | In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The objective of this study was to validate methods used to correct mortality estimates for loss-to-follow-up using a cohort with complete death ascertainment.
Routinely collected data from HIV patients initiating first line antiretroviral therapy (ART) at the Infectious Diseases Institute (IDI) (Routine Cohort) was used. Three methods to estimate mortality after initiation were: 1) standard Kaplan-Meier estimation (uncorrected method) that uses passively observed data; 2) double-sampling methods by Frangakis and Rubin (F&R) where deaths obtained from patient tracing studies are given a higher weight than those passively ascertained; 3) Nomogram proposed by Egger et al. Corrected mortality estimates in the Routine Cohort, were compared with the estimates from the IDI research observational cohort (Research Cohort), which was used as the "gold-standard".
We included 5,633 patients from the Routine Cohort and 559 from the Research Cohort. Uncorrected mortality estimates (95% confidence interval [1]) in the Routine Cohort at 1, 2 and 3 years were 5.5% (4.9%-6.3%), 6.6% (5.9%-7.5%) and 7.4% (6.5%-8.5%), respectively. The F&R corrected estimates at 1, 2 and 3 years were 11.2% (5.8%-21.2%), 15.8% (9.9%-24.8%) and 18.5% (12.3% -27.2%) respectively. The estimates obtained from the Research Cohort were 15.6% (12.8%-18.9%), 17.5% (14.6%-21.0%) and 19.0% (15.3%-21.9%) at 1, 2 and 3 years respectively. Using the nomogram method in the Routine Cohort, the corrected programme-level mortality estimate in year 1 was 11.9% (8.0%-15.7%).
Mortality adjustments provided by the F&R and nomogram methods are adequate and should be employed to correct mortality for loss-to-follow-up in large HIV care centres in Sub-Saharan Africa. |
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| AbstractList | In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The objective of this study was to validate methods used to correct mortality estimates for loss-to-follow-up using a cohort with complete death ascertainment. Routinely collected data from HIV patients initiating first line antiretroviral therapy (ART) at the Infectious Diseases Institute (IDI) (Routine Cohort) was used. Three methods to estimate mortality after initiation were: 1) standard Kaplan-Meier estimation (uncorrected method) that uses passively observed data; 2) double-sampling methods by Frangakis and Rubin (F&R) where deaths obtained from patient tracing studies are given a higher weight than those passively ascertained; 3) Nomogram proposed by Egger et al. Corrected mortality estimates in the Routine Cohort, were compared with the estimates from the IDI research observational cohort (Research Cohort), which was used as the "gold-standard". We included 5,633 patients from the Routine Cohort and 559 from the Research Cohort. Uncorrected mortality estimates (95% confidence interval [1]) in the Routine Cohort at 1, 2 and 3 years were 5.5% (4.9%-6.3%), 6.6% (5.9%-7.5%) and 7.4% (6.5%-8.5%), respectively. The F&R corrected estimates at 1, 2 and 3 years were 11.2% (5.8%-21.2%), 15.8% (9.9%-24.8%) and 18.5% (12.3% -27.2%) respectively. The estimates obtained from the Research Cohort were 15.6% (12.8%-18.9%), 17.5% (14.6%-21.0%) and 19.0% (15.3%-21.9%) at 1, 2 and 3 years respectively. Using the nomogram method in the Routine Cohort, the corrected programme-level mortality estimate in year 1 was 11.9% (8.0%-15.7%). Mortality adjustments provided by the F&R and nomogram methods are adequate and should be employed to correct mortality for loss-to-follow-up in large HIV care centres in Sub-Saharan Africa. Background In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The objective of this study was to validate methods used to correct mortality estimates for loss-to-follow-up using a cohort with complete death ascertainment. Methods Routinely collected data from HIV patients initiating first line antiretroviral therapy (ART) at the Infectious Diseases Institute (IDI) (Routine Cohort) was used. Three methods to estimate mortality after initiation were: 1) standard Kaplan-Meier estimation (uncorrected method) that uses passively observed data; 2) double-sampling methods by Frangakis and Rubin (F&R) where deaths obtained from patient tracing studies are given a higher weight than those passively ascertained; 3) Nomogram proposed by Egger et al. Corrected mortality estimates in the Routine Cohort, were compared with the estimates from the IDI research observational cohort (Research Cohort), which was used as the “gold-standard”. Results We included 5,633 patients from the Routine Cohort and 559 from the Research Cohort. Uncorrected mortality estimates (95% confidence interval [1]) in the Routine Cohort at 1, 2 and 3 years were 5.5% (4.9%–6.3%), 6.6% (5.9%–7.5%) and 7.4% (6.5%–8.5%), respectively. The F&R corrected estimates at 1, 2 and 3 years were 11.2% (5.8%–21.2%), 15.8% (9.9%–24.8%) and 18.5% (12.3% –27.2%) respectively. The estimates obtained from the Research Cohort were 15.6% (12.8%–18.9%), 17.5% (14.6%–21.0%) and 19.0% (15.3%–21.9%) at 1, 2 and 3 years respectively. Using the nomogram method in the Routine Cohort, the corrected programme-level mortality estimate in year 1 was 11.9% (8.0%–15.7%). Conclusion Mortality adjustments provided by the F&R and nomogram methods are adequate and should be employed to correct mortality for loss-to-follow-up in large HIV care centres in Sub-Saharan Africa. Background In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The objective of this study was to validate methods used to correct mortality estimates for loss-to-follow-up using a cohort with complete death ascertainment. Methods Routinely collected data from HIV patients initiating first line antiretroviral therapy (ART) at the Infectious Diseases Institute (IDI) (Routine Cohort) was used. Three methods to estimate mortality after initiation were: 1) standard Kaplan-Meier estimation (uncorrected method) that uses passively observed data; 2) double-sampling methods by Frangakis and Rubin (F&R) where deaths obtained from patient tracing studies are given a higher weight than those passively ascertained; 3) Nomogram proposed by Egger et al. Corrected mortality estimates in the Routine Cohort, were compared with the estimates from the IDI research observational cohort (Research Cohort), which was used as the “gold-standard”. Results We included 5,633 patients from the Routine Cohort and 559 from the Research Cohort. Uncorrected mortality estimates (95% confidence interval [1]) in the Routine Cohort at 1, 2 and 3 years were 5.5% (4.9%–6.3%), 6.6% (5.9%–7.5%) and 7.4% (6.5%–8.5%), respectively. The F&R corrected estimates at 1, 2 and 3 years were 11.2% (5.8%–21.2%), 15.8% (9.9%–24.8%) and 18.5% (12.3% –27.2%) respectively. The estimates obtained from the Research Cohort were 15.6% (12.8%–18.9%), 17.5% (14.6%–21.0%) and 19.0% (15.3%–21.9%) at 1, 2 and 3 years respectively. Using the nomogram method in the Routine Cohort, the corrected programme-level mortality estimate in year 1 was 11.9% (8.0%–15.7%). Conclusion Mortality adjustments provided by the F&R and nomogram methods are adequate and should be employed to correct mortality for loss-to-follow-up in large HIV care centres in Sub-Saharan Africa. BACKGROUNDIn sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The objective of this study was to validate methods used to correct mortality estimates for loss-to-follow-up using a cohort with complete death ascertainment. METHODSRoutinely collected data from HIV patients initiating first line antiretroviral therapy (ART) at the Infectious Diseases Institute (IDI) (Routine Cohort) was used. Three methods to estimate mortality after initiation were: 1) standard Kaplan-Meier estimation (uncorrected method) that uses passively observed data; 2) double-sampling methods by Frangakis and Rubin (F&R) where deaths obtained from patient tracing studies are given a higher weight than those passively ascertained; 3) Nomogram proposed by Egger et al. Corrected mortality estimates in the Routine Cohort, were compared with the estimates from the IDI research observational cohort (Research Cohort), which was used as the "gold-standard". RESULTSWe included 5,633 patients from the Routine Cohort and 559 from the Research Cohort. Uncorrected mortality estimates (95% confidence interval [1]) in the Routine Cohort at 1, 2 and 3 years were 5.5% (4.9%-6.3%), 6.6% (5.9%-7.5%) and 7.4% (6.5%-8.5%), respectively. The F&R corrected estimates at 1, 2 and 3 years were 11.2% (5.8%-21.2%), 15.8% (9.9%-24.8%) and 18.5% (12.3% -27.2%) respectively. The estimates obtained from the Research Cohort were 15.6% (12.8%-18.9%), 17.5% (14.6%-21.0%) and 19.0% (15.3%-21.9%) at 1, 2 and 3 years respectively. Using the nomogram method in the Routine Cohort, the corrected programme-level mortality estimate in year 1 was 11.9% (8.0%-15.7%). CONCLUSIONMortality adjustments provided by the F&R and nomogram methods are adequate and should be employed to correct mortality for loss-to-follow-up in large HIV care centres in Sub-Saharan Africa. In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The objective of this study was to validate methods used to correct mortality estimates for loss-to-follow-up using a cohort with complete death ascertainment. Routinely collected data from HIV patients initiating first line antiretroviral therapy (ART) at the Infectious Diseases Institute (IDI) (Routine Cohort) was used. Three methods to estimate mortality after initiation were: 1) standard Kaplan-Meier estimation (uncorrected method) that uses passively observed data; 2) double-sampling methods by Frangakis and Rubin (F&R) where deaths obtained from patient tracing studies are given a higher weight than those passively ascertained; 3) Nomogram proposed by Egger et al. Corrected mortality estimates in the Routine Cohort, were compared with the estimates from the IDI research observational cohort (Research Cohort), which was used as the "gold-standard". We included 5,633 patients from the Routine Cohort and 559 from the Research Cohort. Uncorrected mortality estimates (95% confidence interval [1]) in the Routine Cohort at 1, 2 and 3 years were 5.5% (4.9%-6.3%), 6.6% (5.9%-7.5%) and 7.4% (6.5%-8.5%), respectively. The F&R corrected estimates at 1, 2 and 3 years were 11.2% (5.8%-21.2%), 15.8% (9.9%-24.8%) and 18.5% (12.3% -27.2%) respectively. The estimates obtained from the Research Cohort were 15.6% (12.8%-18.9%), 17.5% (14.6%-21.0%) and 19.0% (15.3%-21.9%) at 1, 2 and 3 years respectively. Using the nomogram method in the Routine Cohort, the corrected programme-level mortality estimate in year 1 was 11.9% (8.0%-15.7%). Mortality adjustments provided by the F&R and nomogram methods are adequate and should be employed to correct mortality for loss-to-follow-up in large HIV care centres in Sub-Saharan Africa. |
| Audience | Academic |
| Author | Kambugu, Andrew Kiwanuka, Noah Yiannoutsos, Constantin T Manabe, Yukari C Levin, Jonathan Castelnuovo, Barbara Kiragga, Agnes N Musomba, Rachel |
| AuthorAffiliation | Technische Universität Dresden, Germany 5 School of Public Health, College of Health Sciences, Makerere University Kampala, Uganda 2 Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe, Uganda 3 School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America 4 Indiana University Richard M. Fairbanks School of Public Health, Department of Biostatistics, Indianapolis, Indiana, United States of America 1 Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda |
| AuthorAffiliation_xml | – name: 5 School of Public Health, College of Health Sciences, Makerere University Kampala, Uganda – name: 1 Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda – name: 2 Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe, Uganda – name: 4 Indiana University Richard M. Fairbanks School of Public Health, Department of Biostatistics, Indianapolis, Indiana, United States of America – name: 3 School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America – name: Technische Universität Dresden, Germany |
| Author_xml | – sequence: 1 givenname: Agnes N surname: Kiragga fullname: Kiragga, Agnes N organization: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda – sequence: 2 givenname: Barbara surname: Castelnuovo fullname: Castelnuovo, Barbara organization: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda – sequence: 3 givenname: Rachel surname: Musomba fullname: Musomba, Rachel organization: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda – sequence: 4 givenname: Jonathan surname: Levin fullname: Levin, Jonathan organization: Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe, Uganda – sequence: 5 givenname: Andrew surname: Kambugu fullname: Kambugu, Andrew organization: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda – sequence: 6 givenname: Yukari C surname: Manabe fullname: Manabe, Yukari C organization: School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America – sequence: 7 givenname: Constantin T surname: Yiannoutsos fullname: Yiannoutsos, Constantin T organization: Indiana University Richard M. Fairbanks School of Public Health, Department of Biostatistics, Indianapolis, Indiana, United States of America – sequence: 8 givenname: Noah surname: Kiwanuka fullname: Kiwanuka, Noah organization: School of Public Health, College of Health Sciences, Makerere University Kampala, Uganda |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24391780$$D View this record in MEDLINE/PubMed |
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| Copyright | COPYRIGHT 2013 Public Library of Science 2013 Kiragga et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2013 Kiragga et al 2013 Kiragga et al |
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| DocumentTitleAlternate | Methods for Correction of HIV Mortality Estimates |
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| Editor | Kaderali, Lars |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Undefined-2 Competing Interests: The authorts have declared that no competing interests exist. Conceived and designed the experiments: A. Kiragga. Analyzed the data: A. Kiragga CTY. Contributed reagents/materials/analysis tools: A. Kiragga CTY NK. Wrote the paper: A. Kiragga BC RM JL YCM A. Kambugu CTY NK. |
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| References_xml | – volume: 53 start-page: 405 year: 2010 ident: ref20 article-title: Understanding reasons for and outcomes of patients lost to follow-up in antiretroviral therapy programs in Africa through a sampling-based approach publication-title: J Acquir Immune Defic Syndr doi: 10.1097/QAI.0b013e3181b843f0 contributor: fullname: EH Geng – volume: 365 start-page: 2077 year: 2005 ident: ref2 article-title: The two sides of PEPFAR in Uganda publication-title: Lancet doi: 10.1016/S0140-6736(05)66717-7 contributor: fullname: E Bass – volume: 8 start-page: e1000390 year: 2011 ident: ref1 article-title: Correcting mortality for loss to follow-up: a nomogram applied to antiretroviral treatment programmes in sub-Saharan Africa publication-title: PLoS Med doi: 10.1371/journal.pmed.1000390 contributor: fullname: M Egger – volume: 6 start-page: e14684 year: 2011 ident: ref10 article-title: Correcting for mortality among patients lost to follow up on antiretroviral therapy in South Africa: a cohort analysis publication-title: PLoS One doi: 10.1371/journal.pone.0014684 contributor: fullname: G Van Cutsem – ident: ref7 – volume: 7 start-page: e31706 year: 2012 ident: ref4 article-title: Comparison of methods to correct survival estimates and survival regression analysis on a large HIV African cohort publication-title: PLoS One doi: 10.1371/journal.pone.0031706 contributor: fullname: J Henriques – volume: 367 start-page: 817 year: 2006 ident: ref6 article-title: Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries publication-title: Lancet doi: 10.1016/S0140-6736(06)68337-2 contributor: fullname: P Braitstein – volume: 65 start-page: 301 year: 2009 ident: ref5 article-title: The need for double-sampling designs in survival studies: an application to monitor PEPFAR publication-title: Biometrics doi: 10.1111/j.1541-0420.2008.01043.x contributor: fullname: MW An – volume: 30 start-page: 377 year: 2011 ident: ref16 article-title: Multiple imputation using chained equations: Issues and guidance for practice publication-title: Stat Med doi: 10.1002/sim.4067 contributor: fullname: IR White – volume: 49 start-page: 965 year: 2009 ident: ref15 article-title: Cause-specific mortality and the contribution of immune reconstitution inflammatory syndrome in the first 3 years after antiretroviral therapy initiation in an urban African cohort publication-title: Clin Infect Dis doi: 10.1086/605500 contributor: fullname: B Castelnuovo – volume: 26 start-page: 365 year: 2012 ident: ref19 article-title: Mortality and loss to follow-up in the first year of ART: Malawi national ART programme publication-title: AIDS doi: 10.1097/QAD.0b013e32834ed814 contributor: fullname: R Weigel – ident: ref21 doi: 10.1002/sim.5912 – volume: 300 start-page: 506 year: 2008 ident: ref8 article-title: Sampling-based approach to determining outcomes of patients lost to follow-up in antiretroviral therapy scale-up programs in Africa publication-title: JAMA doi: 10.1001/jama.300.5.506 contributor: fullname: EH Geng – volume: 17 start-page: 497 year: 2012 ident: ref11 article-title: Low mortality risk but high loss to follow-up among patients in the Tanzanian national HIV care and treatment programme publication-title: Trop Med Int Health doi: 10.1111/j.1365-3156.2011.02952.x contributor: fullname: G Somi – volume: 4 start-page: e298 year: 2007 ident: ref3 article-title: Patient retention in antiretroviral therapy programs in sub-Saharan Africa: a systematic review publication-title: PLoS Med doi: 10.1371/journal.pmed.0040298 contributor: fullname: S Rosen – volume: 3 start-page: e3843 year: 2008 ident: ref17 article-title: Sampling-based approaches to improve estimation of mortality among patient dropouts: experience from a large PEPFAR-funded program in Western Kenya publication-title: PLoS One doi: 10.1371/journal.pone.0003843 contributor: fullname: CT Yiannoutsos – volume: 57 start-page: 333 year: 2001 ident: ref9 article-title: Addressing an idiosyncrasy in estimating survival curves using double sampling in the presence of self-selected right censoring publication-title: Biometrics doi: 10.1111/j.0006-341X.2001.00333.x contributor: fullname: CE Frangakis – volume: 46 start-page: 187 year: 2007 ident: ref14 article-title: Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy publication-title: J Acquir Immune Defic Syndr doi: 10.1097/QAI.0b013e31814278c0 contributor: fullname: MR Kamya – ident: ref18 – ident: ref12 – volume: 5 start-page: e10527 year: 2010 ident: ref13 article-title: Incident tuberculosis during antiretroviral therapy contributes to suboptimal immune reconstitution in a large urban HIV clinic in sub-Saharan Africa publication-title: PLoS One doi: 10.1371/journal.pone.0010527 contributor: fullname: SM Hermans |
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| Snippet | In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The objective... Background In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The... BACKGROUNDIn sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The... Background In sub-Saharan Africa, a large proportion of HIV positive patients on antiretroviral therapy (ART) are lost to follow-up, some of whom are dead. The... |
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| SubjectTerms | Acquired immune deficiency syndrome Adult AIDS Analysis Anti-HIV Agents - therapeutic use Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Cohort Studies Communicable diseases Confidence Intervals Drug therapy Estimates Female Follow-Up Studies Health aspects Health sciences Highly active antiretroviral therapy HIV HIV Infections - drug therapy HIV Infections - mortality Human immunodeficiency virus Humans Infectious diseases Kaplan-Meier Estimate Lost to Follow-Up Male Medical research Medicine Methods Mortality Nomograms Patients Public health Sampling methods Therapy Uganda - epidemiology |
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| Title | Comparison of methods for correction of mortality estimates for loss to follow-up after ART initiation: a case of the Infectious Diseases Institute, Uganda |
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