title: Risk factors for mortality during antiretroviral therapy in older populations in resource-limited settings.
abstract: BACKGROUND
  An increasing proportion of adult patients initiating antiretroviral therapy (ART) in resource-limited settings are aged > 50 years. Older populations on ART appear to have heightened risk of death, but little is known about factors influencing mortality in this population.
  
  
  METHODS
  We performed a retrospective observational multisite cohort study including all adult patients (≥ 15 years) initiating ART between 2003 and 2013 in programmes supported by Médecins Sans Frontières across 12 countries in Asia, Africa and Europe. Patients were stratified into two age groups, > 50 years and 15 to 50 years. A Cox proportional hazards model was used to explore factors associated with mortality.
  
  
  RESULTS
  The study included 41,088 patients: 2591 (6.3%) were aged > 50 years and 38,497 (93.7%) were aged 15 to 50 years. The mortality rate was significantly higher in the age group > 50 years [367 (14.2%) deaths; mortality rate 7.67 deaths per 100 person-years (95% confidence interval, CI: 6.93 to 8.50)] compared to the age group 15 to 50 years [3788 (9.8%) deaths; mortality rate 4.18 deaths per 100 person-years (95% CI: 4.05 to 4.31)], p < 0.0001. Higher CD4 levels at baseline were associated with significantly reduced mortality rates in the 15 to 50 age group but this association was not seen in the > 50 age group. WHO Stage 4 conditions were more strongly associated with increased mortality rates in the 15 to 50 age group compared to populations > 50 years. WHO Stage 3 conditions were associated with an increased mortality rate in the 15 to 50 age group but not in the > 50 age group. Programme region did not affect mortality rates in the > 50 age group; however being in an Asian programme was associated with a 36% reduced mortality rate in populations aged 15 to 50 years compared to being in an African programme. There was a higher overall incidence of Stage 3 WHO conditions in people > 50 years (12.8/100 person-years) compared to those 15 to 50 years (8.1/100 person-years) (p < 0.01). The rate of Stage 4 WHO conditions was similar (5.8/100 versus 6.1/100 respectively, p = 0.52). Mortality rates on ART associated with the majority of specific WHO conditions were similar between the 15 to 50 and > 50 age groups.
  
  
  CONCLUSIONS
  Older patients on ART in resource-limited settings have increased mortality rates, but compared to younger populations this appears to be less influenced by baseline CD4 count and WHO clinical stage. HIV treatment programmes in resource-limited settings need to consider risk factors associated with mortality on ART in older populations, which may differ to those related to younger adults.
authors.affiliation: Manson Unit, Médecins Sans Frontières, London, United Kingdom.|Department of Medicine and Infectious Diseases, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia.|Department of Infectious Diseases, Geelong Hospital, Geelong, Australia; Daniel.obrien@amsterdam.msf.org.
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Brien
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.|Centre for Population Health, Burnet Institute, Melbourne, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.affiliation: Manson Unit, Médecins Sans Frontières, London, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Greig
authors.affiliation: Infectious Diseases Unit, Alfred Hospital, Melbourne, Australia.
authors.forename: James
authors.initials: J
authors.lastname: McMahon
authors.affiliation: Manson Unit, Médecins Sans Frontières, London, United Kingdom.
authors.forename: Charles
authors.initials: C
authors.lastname: Ssonko
authors.affiliation: Public Health Department, Médecins Sans Frontières, Amsterdam, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Casas
authors.affiliation: Public Health Department, Médecins Sans Frontières, Amsterdam, The Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: Mesic
authors.affiliation: Manson Unit, Médecins Sans Frontières, London, United Kingdom.
authors.forename: Philipp
authors.initials: P
authors.lastname: Du Cros
authors.affiliation: Centre for Infectious Diseases Epidemiology Research, University of Cape Town, Cape Town, South Africa.
authors.forename: Nathan
authors.initials: N
authors.lastname: Ford
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality*; D006295:Health Resources; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors
keywords: Africa; Asia; antiretroviral therapy; mortality; older populations; opportunistic infections