Adjusting mortality for loss to follow-up: Analysis of five art programmes in sub-saharan africa

Martin W G Brinkhof, Ben D. Spycher, Constantin Yiannoutsos, Ralf Weigel, Robin Wood, Eugene Messou, Andrew Boulle, Matthias Egger, Jonathan A C Sterne

Research output: Contribution to journalArticle

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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. Methods and Findings: Treatment-nai{dotless}̈ve patients starting combination ART in five programmes in Cô te 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/mL, 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: Nai{dotless}̈ve 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.

Original languageEnglish
Article numbere14149
JournalPLoS One
Volume5
Issue number11
DOIs
StatePublished - 2010

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Africa South of the Sahara
arts
Sub-Saharan Africa
Art
Hazards
Lost to Follow-Up
Mortality
Therapeutics
CD4 Lymphocyte Count
Malawi
program evaluation
Kenya
Program Evaluation
cells
Survival Analysis
South Africa
HIV
Databases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Brinkhof, M. W. G., Spycher, B. D., Yiannoutsos, C., Weigel, R., Wood, R., Messou, E., ... Sterne, J. A. C. (2010). Adjusting mortality for loss to follow-up: Analysis of five art programmes in sub-saharan africa. PLoS One, 5(11), [e14149]. https://doi.org/10.1371/journal.pone.0014149

Adjusting mortality for loss to follow-up : Analysis of five art programmes in sub-saharan africa. / Brinkhof, Martin W G; Spycher, Ben D.; Yiannoutsos, Constantin; Weigel, Ralf; Wood, Robin; Messou, Eugene; Boulle, Andrew; Egger, Matthias; Sterne, Jonathan A C.

In: PLoS One, Vol. 5, No. 11, e14149, 2010.

Research output: Contribution to journalArticle

Brinkhof, MWG, Spycher, BD, Yiannoutsos, C, Weigel, R, Wood, R, Messou, E, Boulle, A, Egger, M & Sterne, JAC 2010, 'Adjusting mortality for loss to follow-up: Analysis of five art programmes in sub-saharan africa', PLoS One, vol. 5, no. 11, e14149. https://doi.org/10.1371/journal.pone.0014149
Brinkhof, Martin W G ; Spycher, Ben D. ; Yiannoutsos, Constantin ; Weigel, Ralf ; Wood, Robin ; Messou, Eugene ; Boulle, Andrew ; Egger, Matthias ; Sterne, Jonathan A C. / Adjusting mortality for loss to follow-up : Analysis of five art programmes in sub-saharan africa. In: PLoS One. 2010 ; Vol. 5, No. 11.
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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. Methods and Findings: Treatment-nai{dotless}̈ve patients starting combination ART in five programmes in C{\^o} te 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/mL, 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: Nai{dotless}̈ve 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.",
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N2 - 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. Methods and Findings: Treatment-nai{dotless}̈ve patients starting combination ART in five programmes in Cô te 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/mL, 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: Nai{dotless}̈ve 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.

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