Universal definition of loss to follow-up in HIV treatment programs: a statistical analysis of 111 facilities in Africa, Asia, and Latin America

Abstract

Background: Although patient attrition is recognized as a threat to the long-term success of antiretroviral therapy programs worldwide, there is no universal definition for classifying patients as lost to follow-up (LTFU). We analyzed data from health facilities across Africa, Asia, and Latin America to empirically determine a standard LTFU definition.

Methods and findings: At a set "status classification" date, patients were categorized as either "active" or "LTFU" according to different intervals from time of last clinic encounter. For each threshold, we looked forward 365 d to assess the performance and accuracy of this initial classification. The best-performing definition for LTFU had the lowest proportion of patients misclassified as active or LTFU. Observational data from 111 health facilities-representing 180,718 patients from 19 countries-were included in this study. In the primary analysis, for which data from all facilities were pooled, an interval of 180 d (95% confidence interval [CI]: 173-181 d) since last patient encounter resulted in the fewest misclassifications (7.7%, 95% CI: 7.6%-7.8%). A secondary analysis that gave equal weight to cohorts and to regions generated a similar result (175 d); however, an alternate approach that used inverse weighting for cohorts based on variance and equal weighting for regions produced a slightly lower summary measure (150 d). When examined at the facility level, the best-performing definition varied from 58 to 383 d (mean=150 d), but when a standard definition of 180 d was applied to each facility, only slight increases in misclassification (mean=1.2%, 95% CI: 1.0%-1.5%) were observed. Using this definition, the proportion of patients classified as LTFU by facility ranged from 3.1% to 45.1% (mean=19.9%, 95% CI: 19.1%-21.7%).

Conclusions: Based on this evaluation, we recommend the adoption of ≥180 d since the last clinic visit as a standard LTFU definition. Such standardization is an important step to understanding the reasons that underlie patient attrition and establishing more reliable and comparable program evaluation worldwide. Please see later in the article for the Editors' Summary.

Figure 1. Best-performing definition for loss to follow-up.

Demonstrated by receiver-operator curves (A) and misclassification (B) in the primary pooled analysis.

Figure 2. Best-performing definition of loss to follow-up by facility.

Each dot represents one facility. Shown with 95% CIs determined via bootstrap modeling and grouped by IeDEA region.

Figure 3. Percentage misclassified at the best-performing definition for loss to follow-up across 111 facilities, grouped by IeDEA region.

The shaded portion of each bar represents the misclassification associated with each facility's best-performing LTFU definition. The white segment shows the incremental increase in misclassification when the proposed standard definition of 180 d was applied to the health center's patient population.

Figure 4. Association between patient volume and optimal definition for loss to follow-up across 111 participating facilities.

The line represents the results of a linear regression model, while the shaded portion represents its 95% CI.

Figure 5. Percentage of patients classified as lost to follow-up at each of 111 participating facilities based on the proposed standard definition of 180 d since last visit, grouped by IeDEA region.