Based on a statistical analysis of 111 facilities in Africa, Asia, and Latin America, Benjamin Chi and colleagues develop a standard loss-to-follow-up (LTFU) definition that can be used by HIV antiretroviral programs worldwide.
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%).
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
Since 1981, AIDS has killed more than 25 million people, and about 33 million people (mostly in low- and middle-income countries) are now infected with HIV, the virus that causes AIDS. Because HIV destroys immune system cells, HIV-positive individuals are very susceptible to other infections, and, early in the AIDS epidemic, most HIV-infected people died within ten years of contracting the virus. Then, in 1996, antiretroviral therapy (ART)—a cocktail of drugs that keeps HIV in check—became available. For people living in developed countries, HIV infection became a chronic condition. However, for people living in developing countries, ART was prohibitively expensive, and HIV/AIDS remained a fatal illness. In 2003, this situation was declared a global emergency, and governments, international agencies, and funding bodies began to implement plans to increase ART coverage in resource-limited countries. By the end of 2009, more than a third of people living in these countries who needed ART were receiving it.
Why Was This Study Done?
Because ART does not cure HIV infection, patients have to take antiretroviral drugs regularly for the rest of their lives. But in some ART programs, more than a third of patients are lost to follow-up (LTFU), that is, they stop coming for treatment, within three years of starting treatment. Patient attrition threatens the success of ART programs, but to understand why it occurs, a standardized method for classifying patients as LTFU is essential. Classification of patients as LTFU relies on an interval-based definition of LTFU. That is, a patient who fails to attend a clinic within a specified interval after a previous visit is classified as LTFU. If this interval is too short, although many patients will be accurately identified as LTFU, there will be a high false-positive rate—some patients classified as LTFU will actually return to the clinic later. Conversely, if the interval is too long, some patients who are truly LTFU will be misclassified as active (a false-negative classification). In this study, the researchers analyzed data from health facilities across Africa, Asia, and Latin America to determine a standard definition for LTFU that minimizes patient misclassification.
What Did the Researchers Do and Find?
Using data collected from 111 health facilities by the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration, the researchers categorized patients receiving ART at each facility at a “status classification” date (12 months before the facility's last data export to IeDEA) as active or LTFU using a range of intervals (thresholds) since their last clinic visit. For example, for a test interval of 200 days, patients who had not revisited the clinic within 200 days of their previous visit at the status classification date were classified as LTFU; patients who had revisited the clinic were classified as active. The researchers then looked forward 365 days from the status classification date to assess the performance and accuracy of these classifications. So, a “LTFU” patient who visited the clinic anytime during the year after the status classification date represented a false-positive classification, and an “active” patient who did not return within the ensuing year represented a false-negative classification. When data from all the facilities were pooled, a threshold of 180 days produced the fewest misclassifications. At the facility level, the best-performing threshold for patient classification ranged from 58 to 383 days (with an average of 150 days), but application of a 180-day threshold to individual facilities only slightly increased misclassifications. Finally, using the 180-day threshold, average LTFU at individual facilities was 19.9%.
What Do These Findings Mean?
Based on these findings, the researchers recommend that the standard definition for LTFU should be when it has been 180 days or more since the patient's last clinic visit. Given the wide range of best-performing definitions among facilities, however, they recognize that local, national, or regional definitions of LTFU may be more appropriate in certain contexts. Adoption of a standard definition for LTFU, the researchers note, should facilitate harmonization of monitoring and evaluation of ART programs across the world and should help to identify “best practices” associated with low LTFU rates. Importantly, it should also provide the necessary framework for research designed to improve patient retention in ART programs, thereby helping to maximize and sustain the health gains from HIV treatment programs.
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001111.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV/AIDS treatment and care and on universal access to AIDS treatment (in English and Spanish)
The World Health Organization provides information about universal access to AIDS treatment (in several languages)
Information about the IeDEA Collaboration available
Patient stories about living with HIV/AIDS are available through Avert and through the charity website Healthtalkonline