The cyclical cascade of HIV care: Temporal care engagement trends within a population-wide cohort.

BACKGROUND: The traditional HIV treatment cascade aims to visualise the journey of each person living with HIV from diagnosis, through initiation on antiretroviral therapy (ART) to treatment success, represented by virological suppression. This representation has been a pivotal tool in highlighting and quantifying sequential gaps along the care continuum. There is longstanding recognition, however, that this may oversimplify the complexity of real-world engagement with HIV services in settings with mature high-burden HIV epidemics. A complementary "cyclical" cascade has been proposed to represent the processes of disengagement at different points on the care continuum, with multiple pathways to re-engagement, although the feasibility of implementing this at scale has been uncertain. This study aimed to populate, refine, and explore the utility of a cyclical representation of the HIV cascade, using routine data from a high-burden HIV setting. METHODS AND FINDINGS: This observational cohort study leveraged person-level data on all people living with HIV in the Western Cape (WC), South Africa, who accessed public health services in the 2 years prior to 31 December 2023. Programme data from disease registers were complemented by data from pharmacy and laboratory systems. At study closure, 494 370 people were included, constituting 93% of those of those estimated to be living with HIV in the province, of whom 355 104 were on ART. Substantial disengagement from HIV care was evident at every point on the cascade. Early treatment emerged as a period of higher risk of disengagement, but it did not account for the majority of disengagement. Almost all those currently disengaged had prior experience of treatment. While re-engagement was also common, overall treatment coverage had increased slowly over 5 years. The transition to dolutegravir-based regimens was dramatic with good virological outcomes for those in care, notwithstanding a clearly discernible impact of the Coronavirus Disease 2019 (COVID-19) pandemic on viral load (VL) testing. People currently engaged and disengaged in care are similar with respect to age and gender. Those who died or disengaged recently were previously distributed across a range of cascade statuses, and a substantial proportion of those newly initiating and re-initiating treatment were no longer on treatment 6 months later. The main limitation of this study was incomplete evidence of HIV testing, linkage to HIV-specific services, and out-of-facility mortality. CONCLUSIONS: Using routine data, it was possible to populate and automate a cyclical cascade of HIV care that continuously captured the nonlinear care journeys of individuals living with HIV. In this generalised mature HIV epidemic, most people are treatment experienced. Disengagement is common and occurs at various points along the cascade, making it challenging to identify high-impact intervention opportunities. While historical HIV cascades remain valuable for target setting and service monitoring, they can be complemented with insights from more detailed cyclical cascades.

The future of HIV testing in eastern and southern Africa: Broader scope, targeted services.

In this Policy Forum, Anna Grimsrud and colleagues discuss the future of HIV testing in eastern and southern Africa, using insights gleaned from a 2021 expert consultation.

The revolving door of HIV care: Revising the service delivery cascade to achieve the UNAIDS 95-95-95 goals.

Peter Ehrenkranz and co-authors present a cyclical cascade of care for people with HIV infection, aiming to facilitate assessment of outcomes.

Emerging priorities for HIV service delivery.

Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services.

Understanding Engagement in HIV Programmes: How Health Services Can Adapt to Ensure No One Is Left Behind.

PURPOSE OF REVIEW: Despite the significant progress in the HIV response, gaps remain in ensuring engagement in care to support life-long medication adherence and viral suppression. This review sought to describe the different points in the HIV care cascade where people living with HIV were not engaging and highlight promising interventions. RECENT FINDINGS: There are opportunities to improve engagement both between testing and treatment and to support re-engagement in care for those in a treatment interruption. The gap between testing and treatment includes people who know their HIV status and people who do not know their status. People in a treatment interruption include those who interrupt immediately following initiation, early on in their treatment (first 6 months) and late (after 6 months or more on ART). For each of these groups, specific interventions are required to support improved engagement. There are diverse needs and specific populations of people living with HIV who are not engaged in care, and differentiated service delivery interventions are required to meet their needs and expectations. For the HIV response to realise the 2030 targets, engagement will need to be supported by quality care and patient choice combined with empowered patients who are treatment literate and have been supported to improve self-management.

The missed potential of CD4 and viral load testing to improve clinical outcomes for people living with HIV in lower-resource settings.

In a Policy Forum, Peter Ehrenkranz and colleagues discuss the contribution of CD4 and viral load testing to outcomes for people with HIV in low- and middle-income countries.

A cluster randomized controlled trial of extending ART refill intervals to six-monthly for anti-retroviral adherence clubs.

BACKGROUND: The antiretroviral therapy (ART) adherence club (AC) differentiated service delivery model, where clinically stable ART patients receive their ART refills and psychosocial support in groups has supported clinically stable patients' retention and viral suppression. Patients and health systems could benefit further by reducing visit frequency and increasing ART refills. We designed a cluster-randomized control trial comparing standard of care (SoC) ACs and six-month ART refill (Intervention) ACs in a large primary care facility in Khayelitsha, South Africa. METHODS: Existing ACs were randomized to either the control (SOC ACs) or intervention (Intervention ACs) arm. SoC ACs meet five times annually, receiving two-month ART refills with a four-month ART refill over year-end. Blood is drawn at the AC visit ahead of the clinical assessment visit. Intervention ACs meet twice annually receiving six-month ART refills, with a third individual visit for routine blood collection anytime two-four weeks before the annual clinical assessment AC visit. Primary outcomes will be retention in care, annual viral load assessment completion and viral load suppression. (<400copies/mL) after 2 years. Ethics approval has been granted by the University of Cape Town (HREC 652/2016) and the Medecins Sans Frontieres (MSF) Ethics Review Board (#1639). Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents. DISCUSSION: Evaluation of an extended ART refill interval in adherence clubs will provide evidence towards novel model adaptions that can be made to further improve convenience for patients and leverage health system efficiencies. TRIAL REGISTRATION: Registered with the Pan African Clinical Trial Registry: PACTR201810631281009. Registered 11 September 2018.

Expansion of the Adherence Club model for stable antiretroviral therapy patients in the Cape Metro, South Africa 2011-2015.

OBJECTIVE: The ambitious '90-90-90' treatment targets require innovative models of care to support quality antiretroviral therapy (ART) delivery. While evidence for differentiated models of ART delivery is growing, there are few data on the feasibility of scale-up. We describe the implementation of the Adherence Club (AC) model across the Cape Metro health district in Cape Town, South Africa, between January 2011 and March 2015. METHODS: Using data from monthly aggregate AC monitoring reports and electronic monitoring systems for the district cohort, we report on the number of facilities offering ACs and the number of patients receiving ART care in the AC model. RESULTS: Between January 2011 and March 2015, the AC programme expanded to reach 32 425 patients in 1308 ACs at 55 facilities. The proportion of the total ART cohort retained in an AC increased from 7.3% at the end of 2011 to 25.2% by March 2015. The number of facilities offering ACs also increased and by the end of the study period, 92.3% of patients were receiving ART at a facility that offered ACs. During this time, the overall ART cohort doubled from 66 616 to 128 697 patients. The implementation of the AC programme offset this increase by 51%. CONCLUSIONS: ACs now provide ART care to more than 30 000 patients. Further expansion of the model will require additional resources and support. More research is necessary to determine the outcomes and quality of care provided in ACs and other differentiated models of ART delivery, especially when implemented at scale.

Do increasing rates of loss to follow-up in antiretroviral treatment programs imply deteriorating patient retention?

In several studies of antiretroviral treatment (ART) programs for persons with human immunodeficiency virus infection, investigators have reported that there has been a higher rate of loss to follow-up (LTFU) among patients initiating ART in recent years than among patients who initiated ART during earlier time periods. This finding is frequently interpreted as reflecting deterioration of patient retention in the face of increasing patient loads. However, in this paper we demonstrate by simulation that transient gaps in follow-up could lead to bias when standard survival analysis techniques are applied. We created a simulated cohort of patients with different dates of ART initiation. Rates of ART interruption, ART resumption, and mortality were assumed to remain constant over time, but when we applied a standard definition of LTFU, the simulated probability of being classified LTFU at a particular ART duration was substantially higher in recently enrolled cohorts. This suggests that much of the apparent trend towards increased LTFU may be attributed to bias caused by transient interruptions in care. Alternative statistical techniques need to be used when analyzing predictors of LTFU--for example, using "prospective" definitions of LTFU in place of "retrospective" definitions. Similar considerations may apply when analyzing predictors of LTFU from treatment programs for other chronic diseases.

Outcomes of a nurse-managed service for stable HIV-positive patients in a large South African public sector antiretroviral therapy programme.

OBJECTIVES: Models of care utilizing task shifting and decentralization are needed to support growing ART programmes. We compared patient outcomes between a doctor-managed clinic and a nurse-managed down-referral site in Cape Town, South Africa. METHODS: Analysis included all adults who initiated ART between 2002 and 2011 within a large public sector ART service. Stable patients were eligible for down-referral. Outcomes [mortality, loss to follow-up (LTFU), virologic failure] were compared under different models of care using proportional hazards models with time-dependent covariates. RESULTS: Five thousand seven hundred and forty-six patients initiated ART and over 5 years 41% (n = 2341) were down-referred; the median time on ART before down-referral was 1.6 years (interquartile range, 0.9-2.6). The nurse-managed down-referral site reported lower crude rates of mortality, LTFU and virologic failure compared with the doctor-managed clinic. After adjustment, there was no difference in the risk of mortality or virologic failure by model of care. However, patients who were down-referred were more likely to be LTFU than those retained at the doctor-managed site (adjusted hazard ratio, 1.36; 95% CI, 1.09-1.69). Increased levels of LTFU in the nurse-managed vs. doctor-managed service were observed in subgroups of male patients, those with advanced disease at initiation and those who started ART in the early years of the programme. CONCLUSION: Reorganization of ART maintenance by down-referral to nurse-managed services is associated with programme outcomes similar to those achieved using doctor-driven primary care services. Further research is necessary to identify optimal models of care to support long-term retention of patients on ART in resource-limited settings.

Factors influencing the implementation of a guideline for re-engagement in HIV care in primary care settings in Johannesburg, South Africa: A qualitative study.

Re-engagement, which involves bringing individuals who have fallen out of HIV care back into treatment, is important in the ongoing care of individuals with HIV, especially in regions with high prevalence and resource limitations. Despite extensive treatment programs, a significant number of people living with HIV in South Africa disengage from care due to different barriers. To address this, the South African Department of Health (DoH) introduced guidelines to support re-engagement. However, while there is a lot of research on factors leading to disengagement, there is a gap in understanding effective strategies for retaining those who re-engage. The objective of this study is to understand the barriers and facilitators influencing the adoption and scalability of strategies for re-engagement in HIV care. Anova Health Institute, in collaboration with the Johannesburg district DoH, launched the Re-engagement Initiative. This initiative aimed to help healthcare providers better understand and implement re-engagement guidelines through capacity-building, clinical decision support tools, mentorship, and data collection. We conducted a qualitative study across nine primary care facilities in Johannesburg to investigate the perspectives of implementing providers. Data collection involved in-depth interviews using semi-structured guides. The Consolidated Framework for Implementation Research (CFIR) was used to analyse factors influencing implementation. Our study identified several factors affecting the implementation of intervention supporting re-engagement guidelines. Leadership was important for driving organizational change, creating the necessary tension for change, and prioritizing the intervention. Knowledge and beliefs about the intervention were also significant; while most providers understood the initiative's objectives and tools, negative attitudes among some hindered adoption. Empathy for client disengagement motivated some providers, while others did not share this understanding. The belief that job aides and re-engagement forms promoted standardized care and improved documentation was a factor in supporting the initiative. Additionally, the alignment of the intervention with existing guidelines, facility plans, and goals influenced its success and sustainability. Our findings offer valuable insights into the opportunities and challenges of implementing intervention to support re-engagement guidelines. They emphasize the need to address negative provider attitudes, foster engaged leadership, and integrate initiatives with broader HIV care program and facility workflows. These insights are important for the adoption and implementation of similar guidelines in similar settings.

Courier delivery of antiretroviral therapy: a cohort study of a South African private-sector HIV programme.

INTRODUCTION: Courier delivery has become a popular antiretroviral therapy (ART) distribution method in some HIV care settings, yet data on ART courier delivery and how it relates to ART outcomes are scarce. We studied the differences in viral suppression rates between individuals from a South African private sector HIV programme receiving ART by courier delivery and those receiving ART through traditional retail dispensing. METHODS: Individuals aged 15 years or older who were actively enrolled in the Aid for AIDS programme between January 2011 and July 2022 were eligible for the analysis. The outcome of interest was viral suppression defined as a viral load (VL) <400 copies per ml. We calculated adjusted odds ratios (OR) for the association between the ART distribution method and viral suppression, comparing those receiving refills through courier pharmacies versus retail dispensing at the time of the VL testing. We used generalized estimating equations to account for repeated VL testing of the same individual. The models were adjusted for age, sex, calendar year, ART regimen, history of mental illness and medical insurance scheme. We computed adjusted ORs for the calendar periods 2011-2013, 2014-2016, 2017-2019, 2020-2022 and overall. RESULTS: We extracted 442,619 VL measurements from 68,720 eligible individuals, 39,406 (57.3%) were women. The median number of VL measurements per individual was 6 (IQR 3-10). VL suppression was detected in 398,901 (90.1%) tests, and 185,701 (42.0%) of the tests were taken while the individual was receiving ART by courier delivery. Overall, courier delivery was associated with 5% higher odds of viral suppression than retail dispensing (adjusted OR 1.05, 95% CI 1.02-1.08). The strength and direction of this association varied by calendar period, with an adjusted OR of 1.37 (95% CI 1.27-1.48) in 2011-2013 and 1.02 (95% CI 0.97-1.07) in 2020-2022. CONCLUSIONS: Courier delivery of ART is a viable alternative to retail dispensing in the South African private sector, as it was associated with higher viral suppression until 2016 and similar suppression rates in recent years. Further research is needed to investigate the potential benefits and drawbacks of courier delivery of ART in both private and public healthcare settings.

Power, data and social accountability: defining a community-led monitoring model for strengthened health service delivery.

INTRODUCTION: Despite international commitment to achieving the end of HIV as a public health threat, progress is off-track and existing gaps have been exacerbated by COVID-19's collision with existing pandemics. Born out of models of political accountability and historical healthcare advocacy led by people living with HIV, community-led monitoring (CLM) of health service delivery holds potential as a social accountability model to increase the accessibility and quality of health systems. However, the effectiveness of the CLM model in strengthening accountability and improving service delivery relies on its alignment with evidence-based principles for social accountability mechanisms. We propose a set of unifying principles for CLM to support the impact on the quality and availability of health services. DISCUSSION: Building on the social accountability literature, core CLM implementation principles are defined. CLM programmes include a community-led and independent data collection effort, in which the data tools and methodology are designed by service users and communities most vulnerable to, and most impacted by, service quality. Data are collected routinely, with an emphasis on prioritizing and protecting respondents, and are then be used to conduct routine and community-led advocacy, with the aim of increasing duty-bearer accountability to service users. CLM efforts should represent a broad and collective community response, led independently by impacted communities, incorporating both data collection and advocacy, and should be understood as a long-term approach to building meaningful engagement in systems-wide improvements rather than discrete interventions. CONCLUSIONS: The CLM model is an important social accountability mechanism for improving the responsiveness of critical health services and systems to communities. By establishing a collective understanding of CLM principles, this model paves the way for improved proliferation of CLM with fidelity of implementation approaches to core principles, rigorous examinations of CLM implementation approaches, impact assessments and evaluations of CLM's influence on service quality improvement.

The importance of the "how": the case for differentiated service delivery of long-acting and extended delivery regimens for HIV prevention and treatment.

INTRODUCTION: Long-acting and extended delivery (LAED) regimens for HIV treatment and prevention offer unique benefits to expand uptake, effective use and adherence. To date, research has focused on basic and clinical science around the safety and efficacy of these products. This commentary outlines opportunities in HIV prevention and treatment programmes, both for the health system and clients, that could be addressed through the inclusion of LAED regimens and the vital role of differentiated service delivery (DSD) in ensuring efficient and equitable access. DISCUSSION: The realities and challenges within HIV treatment and prevention programmes are different. Globally, more than 28 million people are accessing HIV treatment-the vast majority on a daily fixed-dose combination oral pill that is largely available, affordable and well-tolerated. Many people collect extended refills outside of health facilities with clinical consultations once or twice a year. Conversely, uptake of daily oral pre-exposure prophylaxis (PrEP) has consistently missed global targets due to limited access with high individual cost and lack of choice contributing to substantial unmet PrEP need. Recent trends in demedicalization, simplification, additional method options and DSD for PrEP have led to accelerated uptake as its availability has become more aligned with user preferences. How people currently receive HIV treatment and prevention services and their barriers to adherence must be considered for the introduction of LAED regimens to achieve the expected improvements in access and outcomes. Important considerations include the building blocks of DSD: who (provider), where (location), when (frequency) and what (package of services). Ideally, all LAED regimens will leverage DSD models that emphasize access at the community level and self-management. For treatment, LAED regimens may address challenges with adherence but their delivery should provide clear advantages over existing oral products to be scaled. For prevention, LAED regimens expand a potential PrEP user's choice of methods, but like other methods, need to be delivered in a manner that can facilitate frequent re-initiation. CONCLUSIONS: To ensure that innovative LAED HIV treatment and prevention products reach those who most stand to benefit, service delivery and client considerations during development, trial and early implementation are critical.

Attrition from HIV treatment after enrollment in a differentiated service delivery model: A cohort analysis of routine care in Zambia.

BACKGROUND: Many sub-Saharan Africa countries are scaling up differentiated service delivery (DSD) models for HIV treatment to increase access and remove barriers to care. We assessed factors associated with attrition after DSD model enrollment in Zambia, focusing on patient-level characteristics. METHODS: We conducted a retrospective record review using electronic medical records (EMR) of adults (≥15 years) initiated on antiretroviral (ART) between 01 January 2018 and 30 November 2021. Attrition was defined as lost to follow-up (LTFU) or died by November 30, 2021. We categorized DSD models into eight groups: fast-track, adherence groups, community pick-up points, home ART delivery, extended facility hours, facility multi-month dispensing (MMD, 4-6-month ART dispensing), frequent refill care (facility 1-2 month dispensing), and conventional care (facility 3 month dispensing, reference group). We used Fine and Gray competing risk regression to assess patient-level factors associated with attrition, stratified by sex and rural/urban setting. RESULTS: Of 547,281 eligible patients, 68% (n = 372,409) enrolled in DSD models, most commonly facility MMD (n = 306,430, 82%), frequent refill care (n = 47,142, 13%), and fast track (n = 14,433, 4%), with <2% enrolled in the other DSD groups. Retention was higher in nearly all DSD models for all dispensing intervals, compared to the reference group, except fast track for the ≤2 month dispensing group. Retention benefits were greatest for patients in the extended clinic hours group and least for fast track dispensing. CONCLUSION: Although retention in HIV treatment differed by DSD type, dispensing interval, and patient characteristics, nearly all DSD models out-performed conventional care. Understanding the factors that influence the retention of patients in DSD models could provide an important step towards improving DSD implementation.

Providing differentiated service delivery to the ageing population of people living with HIV.

INTRODUCTION: Differentiated service delivery (DSD) models for HIV are a person-centred approach to providing services across the HIV care cascade; DSD has an increasing policy and implementation support in high-burden HIV countries. The life-course approach to DSD for HIV treatment has focused on earlier life phases, childhood and adolescence, families, and supporting sexual and reproductive health during childbearing years. Older adults, defined as those over the age of 50, represent a growing proportion of HIV treatment cohorts with approximately 20% of those supported by PEPFAR in this age band and have specific health needs that differ from younger populations. Despite this, DSD models have not been designed or implemented to address the health needs of older adults. DISCUSSION: Older adults living with HIV are more likely to have significant co-morbid medical conditions. In addition to the commonly discussed co-morbidities of hypertension and diabetes, they are at increased risk of cognitive impairment, frailty and mental health conditions. Age and HIV-related cognitive impairment may necessitate the development of adapted educational materials. Identifying the optimal package of differentiated services to this population, including the frequency of clinical visits, types and location of services is important as is capacitating the healthcare cadres to adapt to these challenges. Technological advances, which have made remote monitoring of adherence and other aspects of disease management easier for younger populations, may not be as readily available or as familiar to older adults. To date, adaptations to service delivery have not been scaled and are limited to nascent programmes working to integrate treatment of common co-morbidities. CONCLUSIONS: Older individuals living with HIV may benefit from a DSD approach that adapts care to the specific challenges of ageing with HIV. Models could be developed and validated using outcome measures, such as viral suppression and treatment continuity. DSD models for older adults should consider their specific health needs, such as high rates of co-morbidities. This may require educational materials, health worker capacity building and outreach designed specifically to treat this age group.

How soon should patients be eligible for differentiated service delivery models for antiretroviral treatment? Evidence from a retrospective cohort study in Zambia.

OBJECTIVES: Patient attrition is high the first 6 months after antiretroviral therapy (ART) initiation. Patients with <6 months of ART are systematically excluded from most differentiated service delivery (DSD) models, which are intended to support retention. Despite DSD eligibility criteria requiring ≥6 months on ART, some patients enrol earlier. We compared loss to follow-up (LTFU) between patients enrolling in DSD models early with those enrolled according to guidelines, assessing whether the ART experience eligibility criterion is necessary. DESIGN: Retrospective cohort study using routinely collected electronic medical record data. SETTING: PARTICIPANTS: Adults (≥15 years) who initiated ART between 1 January 2019 and 31 December 2020. OUTCOMES: LTFU (>30 days late for scheduled visit) at 18 months for 'early enrollers' (DSD enrolment after <6 months on ART) and 'established enrollers' (DSD enrolment after ≥6 months on ART). We used a log-binomial model to compare LTFU risk, adjusting for age, sex, location, ART refill interval and DSD model. RESULTS: For 6340 early enrollers and 25 857 established enrollers, there were no differences in sex (61% female), age (median 37 years) or location (65% urban). ART refill intervals were longer for established versus early enrollers (72% vs 55% were given 4-6 months refills). LTFU at 18 months was 3% (192 of 6340) for early enrollers and 5% (24 646 of 25 857) for established enrollers. Early enrollers were 41% less likely to be LTFU than established patients (adjusted risk ratio 0.59, 95% CI 0.50 to 0.68). CONCLUSIONS: Patients enrolled in DSD after <6 months of ART were more likely to be retained than patients established on ART prior to DSD enrolment. A limitation is that early enrollers may have been selected for DSD due to providers' and patients' expectations about future retention. Offering DSD models to ART patients soon after ART initiation may help address high attrition during the early treatment period. TRIAL REGISTERATION NUMBER: NCT04158882.

The question of the question: impactful implementation science to address the HIV epidemic.

INTRODUCTION: Questions about the implementation of evidence-based intervention to treat and prevent HIV have risen to the top of the field's scientific priorities. Despite the availability of highly efficacious treatment and prevention interventions, impact has fallen short of targets because these interventions are used with insufficient reach, consistency, sustainability and equity in diverse real-world settings. At present, substantial excitement for implementation science - defined as research methods and strategies to improve use of evidence-based interventions - has focused on developing and disseminating methods to conduct rigorous research. Yet, impactful answers depend on a sometimes less visible, but even more important, step: asking good questions about implementation. DISCUSSION: In this commentary, we offer several considerations for researchers formulating implementation research questions based on several distinctive features of the field. First, as findings are used not only by other researchers but by implementers, scientific questions must incorporate a range of stakeholder and community perspectives to be most relevant. Second, real-world settings are contextually diverse, and the most relevant scientific questions must position answers to make sense within these contexts (whether geographical, organizational and sociological), rather than apart from them. Third, implementation is complex and dynamic; consequently, research questions must make use of emerging standards in describing implementation strategies and their effects whenever possible. Finally, the field of implementation science continues to evolve, so framing problems with a diverse disciplinary lens will enable researchers to pose insightful and impactful questions. CONCLUSIONS: We are now at a juncture marked by both rich evidence-based interventions and a persistent global pandemic. To achieve continued scientific progress against the HIV epidemic, asking the right questions might be part of the answer itself.

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

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.