HIV This Week

Adjusting mortality for loss to follow-up: analysis of five ART programmes in sub-Saharan Africa

Brinkhof MW, Spycher BD, Yiannoutsos C, Weigel R, Wood R, Messou E, Boulle A, Egger M, Sterne JA; International epidemiological Database to Evaluate AIDS (IeDEA). PLoS One. 2010 Nov 30;5(11):e14149

Evaluation of antiretroviral treatment antiretroviral therapy 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. The authors adjusted programme-level mortality in the first year of antiretroviral treatment antiretroviral therapy for excess mortality in patients lost to follow-up. Treatment-naïve patients starting combination antiretroviral therapy 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. The authors 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, antiretroviral therapy 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 antiretroviral therapy. 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. Naïve survival analysis ignoring excess mortality in patients lost to follow-up may greatly underestimate overall mortality, and bias antiretroviral therapy programme evaluations. Adjusted mortality estimates can be obtained based on excess mortality rates in patients lost to follow-up.

Abstract

Editors’ note: Loss to follow-up may occur because a patient has died, transport and other costs are too high to continue treatment, HIV-related stigma may have intervened, or treatment adherence has been compromised for other reasons. This research does not focus on how to address loss to follow-up programmatically but rather on how best to adjust antiretroviral programme mortality rates for loss to follow-up. Mortality is the most definitive outcome in life and programmes must strive to measure it correctly and reduce it. The basic question is how much loss to follow-up is due to death. Treating loss to follow-up as a missing data problem, these researchers obtained adjusted mortality estimates used modelling techniques to impute survival times based on plausible estimates from studies that traced individuals lost to follow-up. They report first year adjusted mortality ranging from 10 to 17%. Programmes should adjust their mortality statistics to account for likely rates of mortality among patients lost to follow-up and focus on starting treatment earlier and diagnosing opportunistic infections and cancers in order to bring those mortality rates down.