title: Mortality in patients with HIV-1 infection starting antiretroviral therapy in South Africa, Europe, or North America: a collaborative analysis of prospective studies.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: 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; Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa.
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Schomaker
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Margaret T
authors.initials: MT
authors.lastname: May
authors.affiliation: Division of Epidemiology and Population Health, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada; Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hogg
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.affiliation: Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Monge
authors.affiliation: University of Bern, Institute for Social and Preventive Medicine, Bern, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Keiser
authors.affiliation: Research Department of Infection and Population Health, UCL Medical School, London, United Kingdom.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Lampe
authors.affiliation: McCord Hospital, Durban, South Africa.
authors.forename: Janet
authors.initials: J
authors.lastname: Giddy
authors.affiliation: Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa.
authors.forename: James
authors.initials: J
authors.lastname: Ndirangu
authors.affiliation: Médecins Sans Frontières, Khayelitsha, South Africa.
authors.forename: Daniela
authors.initials: D
authors.lastname: Garone
authors.affiliation: Center for Global Health and Development, Boston University, Boston, Massachusetts, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Fox
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Ingle
authors.affiliation: Stichting HIV Monitoring, Amsterdam, The Netherlands; 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.
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.affiliation: INSERM, Centre INSERM U897 "Epidémiologie et Biostatistique", Bordeaux, France; Université Bordeaux, Institut de Santé Publique Epidémiologie Développement (ISPED), Bordeaux, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Dabis
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.affiliation: Infectious Diseases Department, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.affiliation: First Department of Internal Medicine, University Hospital of Cologne, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Ehren
authors.affiliation: 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; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Colin
authors.initials: C
authors.lastname: Campbell
authors.affiliation: Division of Infectious Diseases, University of Calgary, Calgary, Canada.
authors.forename: M John
authors.initials: MJ
authors.lastname: Gill
authors.affiliation: Division of Infectious Disease, Department of Medicine, University of Alabama, Birmingham, Alabama, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Saag
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, United States of America; VA Connecticut Healthcare System, West Haven, Connecticut, United States of America.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.affiliation: HIV Atlanta VA Cohort Study (HAVACS), Atlanta Veterans Affairs Medical Center, Decatur, Georgia, United States of America.
authors.forename: Jodie
authors.initials: J
authors.lastname: Guest
authors.affiliation: Center for AIDS Research, University of Washington, Seattle, Washington, United States of America.
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Crane
authors.affiliation: 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; University of Bern, Institute for Social and Preventive Medicine, Bern, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Jonathan A C
authors.initials: JA
authors.lastname: Sterne
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000401:mortality* / Q000639:trends*; D015331:Cohort Studies; D003299:Cooperative Behavior; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D009656:North America / Q000453:epidemiology; D011446:Prospective Studies; D013019:South Africa / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents