Abstract
BackgroundLoss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland.Methods and FindingsHIV-infected patients aged ≥18 years who started ART 2004–2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up.ConclusionsIn ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings.
Highlights
In most settings, regular attendance at health facilities is critical to the comprehensive medical care of HIV-infected patients
The CD4 cell count and other prognostic factors may be differentially associated with Loss to follow-up (LTFU) in low-income and high-income settings
We analysed data from two well-described HIV cohorts: a Zambian cohort supported by the Centre for Infectious Disease Research in Zambia (CIDRZ) and the Zambian Ministry of Health [9,17] and the Swiss HIV Cohort Study [4]
Summary
Regular attendance at health facilities is critical to the comprehensive medical care of HIV-infected patients. During these visits, health care workers examine patients for clinical progression, provide and monitor combination antiretroviral therapy (ART), and counsel them on minimizing the risk of HIV transmission. Health care workers examine patients for clinical progression, provide and monitor combination antiretroviral therapy (ART), and counsel them on minimizing the risk of HIV transmission Despite this need for regular monitoring, significant loss to follow-up has been demonstrated in ART programmes and cohort studies – both in industrialized and resource-limited settings – at rates often exceeding reported mortality [1]. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland
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