Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies

High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study...

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Published in:	PLoS medicine Vol. 11; no. 9; p. e1001718
Main Authors:	Boulle, Andrew, Schomaker, Michael, May, Margaret T., Hogg, Robert S., Shepherd, Bryan E., Monge, Susana, Keiser, Olivia, Lampe, Fiona C., Giddy, Janet, Ndirangu, James, Garone, Daniela, Fox, Matthew, Ingle, Suzanne M., Reiss, Peter, Dabis, Francois, Costagliola, Dominique, Castagna, Antonella, Ehren, Kathrin, Campbell, Colin, Gill, M. John, Saag, Michael, Justice, Amy C., Guest, Jodie, Crane, Heidi M., Egger, Matthias, Sterne, Jonathan A. C.
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 01.09.2014 Public Library of Science (PLoS)
Subjects:	Acquired immune deficiency syndrome Adult AIDS Analysis Anti-HIV Agents - therapeutic use Antiretroviral Therapy, Highly Active - mortality Antiretroviral Therapy, Highly Active - trends Antiviral agents Biology and Life Sciences Care and treatment Cohort Studies Cooperative Behavior Drug therapy Europe Europe - epidemiology Female Follow-Up Studies Health aspects Highly active antiretroviral therapy HIV HIV infection HIV Infections - drug therapy HIV Infections - mortality HIV patients HIV-1 Human immunodeficiency virus Human immunodeficiency virus 1 Humans Male Medicine and Health Sciences Middle Aged Mortality Mortality - trends North America North America - epidemiology Patient outcomes Prospective Studies Risk factors South Africa South Africa - epidemiology Studies South Africa North America Europe
ISSN:	1549-1676, 1549-1277, 1549-1676
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Abstract	High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary.
AbstractList	Please see later in the article for the Editors' Summary. Background: High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings: Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 20012010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/ml in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/ml. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. Conclusions: After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary. Analyzing survival in HIV treatment cohorts, Andrew Boulle and colleagues find mortality rates in South Africa comparable to or better than those in North America by 4 years after starting antiretroviral therapy. Please see later in the article for the Editors' Summary High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [SouthAfrica], 29,727 [Europe], and 7,160 [NorthAmerica]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/ mu l in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/ mu l. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary AIDS has killed about 36 million people since the first recorded case of the disease in 1981, and a similar number of people (including 25 million living in sub-Saharan Africa) are currently infected with HIV, the virus that causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other serious infections. Early in the AIDS epidemic, HIV-positive people usually died within 10 years of becoming infected. In 1996, effective antiretroviral therapy (ART) became available and, for people living in high-income countries, HIV infection became a chronic condition. But ART was expensive, so HIV/AIDS remained largely untreated and fatal in resource-limited countries. Then, in 2003, the international community began to work towards achieving universal access to ART. By the end of 2012, nearly two-thirds of HIV-positive people (nearly 10 million individuals) living in low- and middle-income countries who were eligible for treatment because their CD4 cell count had fallen below 350/mm3 blood or because they had developed an AIDS-defining condition were receiving treatment. It is known that a larger proportion of HIV-positive patients starting ART die during the first year of treatment in sub-Saharan Africa than in Europe and North America. This difference arises in part because patients in resource-limited settings tend to have lower CD4 counts when they start treatment than patients in wealthy countries. However, the lack of reliable data on mortality (death) in resource-limited settings has made it hard to compare longer-term outcomes in different settings. Information on the long-term outcomes of HIV-positive patients receiving ART in resource-limited countries is needed to guide the development of appropriate health systems and treatment regimens in these settings. In this collaborative analysis of prospective cohort studies, the researchers compare mortality up to 4 years on ART in South Africa, Europe, and North America. A prospective cohort study follows a group of individuals over time to see whether differences in specific characteristics at the start of the study affect subsequent outcomes. A collaborative analysis combines individual patient data from several studies. The researchers combined data from four South Africa cohorts of HIV-positive patients starting ART included in the International Epidemiologic Databases to Evaluate AIDS South African (IeDEA-SA) collaboration with data from six North American cohorts and nine European cohorts included in the ART Cohort Collaboration (ART-CC). The South African cohorts were chosen because unusually for studies undertaken in countries in sub-Saharan Africa the vital status of patients (whether they had died) who had been lost to follow-up in these cohorts could be obtained from the national population register. Patients in South Africa began treatment with more advanced disease (indicated by a lower average CD4 count) than patients in Europe or North America. Notably, high early mortality after starting ART in South Africa occurred mainly in patients starting ART with a CD4 count below 50 cells/mm3. The cumulative mortality after 4 years of ART was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. After adjusting for patient... Analyzing survival in HIV treatment cohorts, Andrew Boulle and colleagues find mortality rates in South Africa comparable to or better than those in North America by 4 years after starting antiretroviral therapy. Please see later in the article for the Editors' Summary High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.BACKGROUNDHigh early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.METHODS AND FINDINGSData from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary.CONCLUSIONSAfter accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary. High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary. BackgroundHigh early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.Methods and findingsData from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.ConclusionsAfter accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary. Background High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. Conclusions After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary
Audience	Academic
Author	Campbell, Colin Giddy, Janet Egger, Matthias Monge, Susana Saag, Michael Reiss, Peter Hogg, Robert S. Castagna, Antonella Gill, M. John Fox, Matthew Costagliola, Dominique Schomaker, Michael Ehren, Kathrin Keiser, Olivia Justice, Amy C. Sterne, Jonathan A. C. Shepherd, Bryan E. Ingle, Suzanne M. Dabis, Francois Lampe, Fiona C. Guest, Jodie May, Margaret T. Boulle, Andrew Crane, Heidi M. Garone, Daniela Ndirangu, James
AuthorAffiliation	3 School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom 8 University of Bern, Institute for Social and Preventive Medicine, Bern, Switzerland 25 Division of Infectious Disease, Department of Medicine, University of Alabama, Birmingham, Alabama, United States of America 26 Yale University School of Medicine, New Haven, Connecticut, United States of America 19 INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France 22 Centre d'Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), Institut català d'Oncologia (ICO), Agència Salut Pública de Catalunya (ASPC), Generalitat de Catalunya, Badalona, Spain 7 Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain 16 INSERM, Centre INSERM U897 “Epidémiologie et Biostatistique”, Bordeaux, France 1 Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Faculty of Health Scie
AuthorAffiliation_xml	– name: 28 HIV Atlanta VA Cohort Study (HAVACS), Atlanta Veterans Affairs Medical Center, Decatur, Georgia, United States of America – name: 9 Research Department of Infection and Population Health, UCL Medical School, London, United Kingdom – name: 22 Centre d'Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), Institut català d'Oncologia (ICO), Agència Salut Pública de Catalunya (ASPC), Generalitat de Catalunya, Badalona, Spain – name: 13 Center for Global Health and Development, Boston University, Boston, Massachusetts, United States of America – name: Rwanda Ministry of Health, Rwanda – name: 2 Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa – name: 25 Division of Infectious Disease, Department of Medicine, University of Alabama, Birmingham, Alabama, United States of America – name: 3 School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom – name: 19 INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France – name: 20 Infectious Diseases Department, San Raffaele Scientific Institute, Milan, Italy – name: 11 Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa – name: 6 Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America – name: 5 Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada – name: 10 McCord Hospital, Durban, South Africa – name: 14 Stichting HIV Monitoring, Amsterdam, The Netherlands – name: 8 University of Bern, Institute for Social and Preventive Medicine, Bern, Switzerland – name: 15 Department of Global Health and Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, and Amsterdam Institute for Global health and Development, Amsterdam, the Netherlands – name: 17 Université Bordeaux, Institut de Santé Publique Epidémiologie Développement (ISPED), Bordeaux, France – name: 23 CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain – name: 12 Médecins Sans Frontières, Khayelitsha, South Africa – name: 16 INSERM, Centre INSERM U897 “Epidémiologie et Biostatistique”, Bordeaux, France – name: 27 VA Connecticut Healthcare System, West Haven, Connecticut, United States of America – name: 1 Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa – name: 24 Division of Infectious Diseases, University of Calgary, Calgary, Canada – name: 26 Yale University School of Medicine, New Haven, Connecticut, United States of America – name: 29 Center for AIDS Research, University of Washington, Seattle, Washington, United States of America – name: 4 Division of Epidemiology and Population Health, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada – name: 7 Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain – name: 21 First Department of Internal Medicine, University Hospital of Cologne, Germany – name: 18 Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
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Copyright	COPYRIGHT 2014 Public Library of Science 2014 Boulle et al 2014 Boulle et al 2014 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Boulle A, Schomaker M, May MT, Hogg RS, Shepherd BE, Monge S, et al. (2014) Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies. PLoS Med 11(9): e1001718. doi:10.1371/journal.pmed.1001718
Copyright_xml	– notice: COPYRIGHT 2014 Public Library of Science – notice: 2014 Boulle et al 2014 Boulle et al – notice: 2014 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Boulle A, Schomaker M, May MT, Hogg RS, Shepherd BE, Monge S, et al. (2014) Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies. PLoS Med 11(9): e1001718. doi:10.1371/journal.pmed.1001718
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 MSS is the local principal investigator on studies sponsored by Abbvie, Gilead, BMS, Merck, BI, ViiV, and Jannsen, where funding goes directly to the institution but not to MSS. PR, through his institution, has received independent scientific grant support from Gilead Sciences, Janssen Pharmaceutica N.V., Merck&Co, Bristol-Myers Squibb, and ViiV Healthcare, and travel support through his institution from Gilead Sciences and Janssen Pharmaceutica N.V. In addition, PR has served on a scientific advisory board for Gilead Sciences and serves on a data safety monitoring committee for Janssen Pharmaceutica N.V., for which his institution has received remuneration. KE has received honoraria from Abbott for educational lectures. JS has received research grants from the UK Medical Research Council. JS has received payment from Gilead Sciences, Inc for educational presentations. Conceived and designed the experiments: AB MS MTM RSH BES SM OK FL JG JN DG MF SMI PR FD DC AC KE CC MJG MS ACJ JG HMC ME JACS. Analyzed the data: MS AB MM JACS. Wrote the first draft of the manuscript: AB. Contributed to the writing of the manuscript: MS MTM RSH BES SM OK FL JG JN DG MF SMI PR FD DC AC KE CC MJG MS ACJ JG HMC ME JACS. ICMJE criteria for authorship read and met: AB MS MTM RSH BES SM OK FL JG JN DG MF SMI PR FD DC AC KE CC MJG MS ACJ JG HMC ME JACS. Agree with manuscript results and conclusions: AB MS MTM RSH BES SM OK FL JG JN DG MF SMI PR FD DC AC KE CC MJG MS ACJ JG HMC ME JACS.
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Snippet	High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well... Background: High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is... Please see later in the article for the Editors' Summary. Analyzing survival in HIV treatment cohorts, Andrew Boulle and colleagues find mortality rates in South Africa comparable to or better than those in North... BackgroundHigh early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is... Background High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is...
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SubjectTerms	Acquired immune deficiency syndrome Adult AIDS Analysis Anti-HIV Agents - therapeutic use Antiretroviral Therapy, Highly Active - mortality Antiretroviral Therapy, Highly Active - trends Antiviral agents Biology and Life Sciences Care and treatment Cohort Studies Cooperative Behavior Drug therapy Europe Europe - epidemiology Female Follow-Up Studies Health aspects Highly active antiretroviral therapy HIV HIV infection HIV Infections - drug therapy HIV Infections - mortality HIV patients HIV-1 Human immunodeficiency virus Human immunodeficiency virus 1 Humans Male Medicine and Health Sciences Middle Aged Mortality Mortality - trends North America North America - epidemiology Patient outcomes Prospective Studies Risk factors South Africa South Africa - epidemiology Studies
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Title	Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies
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