title: Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa.
abstract: BACKGROUND
  Evaluation of antiretroviral treatment (ART) programmes in sub-Saharan Africa is difficult because many patients are lost to follow-up. Outcomes in these patients are generally unknown but studies tracing patients have shown mortality to be high. We adjusted programme-level mortality in the first year of antiretroviral treatment (ART) for excess mortality in patients lost to follow-up.
  
  
  RESULTS
  Treatment-naïve patients starting combination ART in five programmes in Côte d'Ivoire, Kenya, Malawi and South Africa were eligible. Patients whose last visit was at least nine months before the closure of the database were considered lost to follow-up. We filled missing survival times in these patients by multiple imputation, using estimates of mortality from studies that traced patients lost to follow-up. Data were analyzed using Weibull models, adjusting for age, sex, ART regimen, CD4 cell count, clinical stage and treatment programme. A total of 15,915 HIV-infected patients (median CD4 cell count 110 cells/µL, median age 35 years, 68% female) were included; 1,001 (6.3%) were known to have died and 1,285 (14.3%) were lost to follow-up in the first year of ART. Crude estimates of mortality at one year ranged from 5.7% (95% CI 4.9-6.5%) to 10.9% (9.6-12.4%) across the five programmes. Estimated mortality hazard ratios comparing patients lost to follow-up with those remaining in care ranged from 6 to 23. Adjusted estimates based on these hazard ratios ranged from 10.2% (8.9-11.6%) to 16.9% (15.0-19.1%), with relative increases in mortality ranging from 27% to 73% across programmes.
  
  
  CONCLUSIONS
  Naïve survival analysis ignoring excess mortality in patients lost to follow-up may greatly underestimate overall mortality, and bias ART programme evaluations. Adjusted mortality estimates can be obtained based on excess mortality rates in patients lost to follow-up.
authors.affiliation: Division of International and Environmental Health, Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
authors.forename: Martin W G
authors.initials: MW
authors.lastname: Brinkhof
authors.forename: Ben D
authors.initials: BD
authors.lastname: Spycher
authors.forename: Constantin
authors.initials: C
authors.lastname: Yiannoutsos
authors.forename: Ralf
authors.initials: R
authors.lastname: Weigel
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Eugène
authors.initials: E
authors.lastname: Messou
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Jonathan A C
authors.initials: JA
authors.lastname: Sterne
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D007560:Cote d'Ivoire / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D007630:Kenya / Q000453:epidemiology; D059012:Lost to Follow-Up; D008295:Malawi / Q000453:epidemiology; D008297:Male; D013019:South Africa / Q000453:epidemiology; D015996:Survival Rate
chemical_list: D000998:Antiviral Agents