HIV care experiences and health priorities during the first wave of COVID-19: clients' perspectives - a qualitative study in Lusaka, Zambia.

BACKGROUND: The novel COVID-19 pandemic threatened to disrupt access to human immunodeficiency (HIV) treatment for persons living with HIV (PLHIV), two-thirds of whom live in sub-Saharan Africa. To inform a health system response supportive of continuity of care, we sought to understand clients' HIV care experiences and health priorities during the first wave of COVID-19 outbreak in Lusaka, Zambia. METHODS: Leveraging a study cohort of those who completed periodic SMS surveys on HIV care, we purposefully sampled 25 PLHIV after first confirmed COVID-19 case was reported in Zambia on 18th March 2020. We phone-interviewed participants, iteratively refining interview guide to capture emergent themes on COVID-19 awareness, health facility interactions, and social circumstances, which we analyzed using matrix analysis. RESULTS: All participants were aware of COVID-19, and HIV care experiences and health priorities of clients were affected by associated changes at health system, household, and individual level. The health system instituted early clinic visits to provide 6-months of antiretroviral therapy (ART) for stable patients and 3-months for unstable patients to reduce clinic visits and wait times. Most patients welcomed this long-desired extended appointment spacing. Some reported feeling respected and engaged when health care workers telephoned requesting their early clinic visit. However, others felt discouraged by an absence of physical distancing during their clinic visit due to 'severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2) infection concerns. Several expressed a lack of clarity regarding next viral load monitoring date and means for receiving results. Patients suggested regular patient-facility communication by telephone and SMS. Patients emphasized that COVID-19 restrictions led to loss of employment and household income, exacerbating poverty and difficulties in taking ART. At individual level, most participants felt motivated to stay healthy during COVID-19 by ART adherence and regular laboratory monitoring. CONCLUSIONS: Clients' HIV care and health priorities during the first wave of COVID-19 in Lusaka province were varied with a combination of positive and negative experiences that occurred especially at health system and individual levels, while at household level, the experiences were all negative. More research is needed to understand how patients practice resiliency in the widespread context of socio-economic instability. Governments and patients must work together to find local, health systems solutions to support ART adherence and monitoring. Additionally, the health system should consider how to build on changes for long-term HIV management and service delivery.

Patient-reported Reasons for Stopping Care or Switching Clinics in Zambia: A Multisite, Regionally Representative Estimate Using a Multistage Sampling-based Approach in Zambia.

BACKGROUND: Understanding patient-reported reasons for lapses of retention in human immunodeficiency virus (HIV) treatment can drive improvements in the care cascade. A systematic assessment of outcomes among a random sample of patients lost to follow-up (LTFU) from 32 clinics in Zambia to understand the reasons for silent transfers and disengagement from care was undertaken. METHODS: We traced a simple random sample of LTFU patients (>90 days from last scheduled visit) as determined from clinic-based electronic medical records from a probability sample of facilities. Among patients found in person, we solicited reasons for either stopping or switching care and predictors for re-engagement. We coded reasons into structural, psychosocial, and clinic-based barriers. RESULTS: Among 1751 LTFU patients traced and found alive, 31% of patients starting antiretroviral therapy (ART) between 1 July 2013 and 31 July 2015 silently transferred or were disengaged (40% male; median age, 35 years; median CD4 level, 239 cells/µL); median time on ART at LTFU was 480 days (interquartile range, 110-1295). Among the 544 patients not in care, median prevalences for patient-reported structural, psychosocial, and clinic-level barriers were 27.3%, 13.9%, and 13.4%, respectively, and were highly variable across facilities. Structural reasons, including, "relocated to a new place" were mostly cited among 289 patients who silently transferred (35.5%). We found that men were less likely to re-engage in care than women (odds ratio, .39; 95% confidence interval, .22-.67; P = .001). CONCLUSIONS: Efforts to improve retention of patients on ART may need to be tailored at the facility level to address patient-reported barriers.

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.

Longitudinal Care Cascade Outcomes Among People Eligible for Antiretroviral Therapy Who Are Newly Linking to Care in Zambia: A Multistate Analysis.

BACKGROUND: Retention in human immunodeficiency virus (HIV) care is dynamic, with patients frequently transitioning in and out of care. Analytical approaches (eg, survival analyses) commonly used to assess HIV care cascade outcomes fail to capture such transitions and therefore incompletely represent care outcomes over time. METHODS: We analyzed antiretroviral therapy (ART)-eligible adults newly linking to care at 64 clinics in Zambia between 1 April 2014 and 31 July 2015. We used electronic medical record data and supplemented these with updated care outcomes ascertained by tracing a multistage random sample of patients lost to follow-up (LTFU, >90 days late for last appointment). We performed multistate analyses, incorporating weights from sampling, to estimate the prevalence of 9 care states over time since linkage with respect to ART initiation, retention in care, transfers, and mortality. RESULTS: In sum, 23 227 patients (58% female; median age 34 years [interquartile range 28-41]) were ART-eligible at enrollment. At 1 year, 75.2% had initiated ART and were in care: 61.8% were continuously retained, 6.1% had reengaged after LTFU, and 7.3% had transferred. Also, 10.1% were LTFU within 7 days of enrollment, and 15.2% were LTFU at 1 year (6.7% prior to ART). One year after LTFU, 51.6% of those LTFU prior to ART remained out of care compared to 30.2% of those LTFU after initiating ART. Overall, 6.9% of patients had died by 1 year with 3.0% dying prior to ART. CONCLUSION: Multistate analyses provide more complete assessments of longitudinal HIV cascade outcomes and reveal treatment gaps at distinct timepoints in care that will still need to be addressed even with universal treatment.

Mortality estimates by age and sex among persons living with HIV after ART initiation in Zambia using electronic medical records supplemented with tracing a sample of lost patients: A cohort study.

BACKGROUND: Men in sub-Saharan Africa have lower engagement and retention in HIV services compared to women, which may result in differential survival. However, the true magnitude of difference in HIV-related mortality between men and women receiving antiretroviral therapy (ART) is incompletely characterized. METHODS AND FINDINGS: We evaluated HIV-positive adults ≥18 years old newly initiating ART in 4 Zambian provinces (Eastern, Lusaka, Southern, and Western). In addition to mortality data obtained from routine electronic medical records, we intensively traced a random sample of patients lost to follow-up (LTFU) and incorporated tracing outcomes through inverse probability weights. Sex-specific mortality rates and rate differences were determined using Poisson regression. Parametric g-computation was used to estimate adjusted mortality rates by sex and age. The study included 49,129 adults newly initiated on ART between August 2013 and July 2015; overall, the median age among patients was 35 years, the median baseline CD4 count was 262 cells/µl, and 37.2% were men. Men comprised a smaller proportion of individuals starting ART (37.2% versus 62.8%), tended to be older (median age 37 versus 33 years), and tended to have lower CD4 counts (median 220 versus 289 cells/µl) at the time of ART initiation compared to women. The overall rate of mortality among men was 10.3 (95% CI 8.2-12.4) deaths/100 person-years (PYs), compared to 5.5 (95% CI 4.3-6.8) deaths/100 PYs among women (difference +4.7 [95% CI 2.3-7.2] deaths/100 PYs; p < 0.001). Compared to women in the same age groups, men's mortality rates were particularly elevated among those <30 years old (+6.7 deaths/100 PYs difference), those attending rural health centers (+9.4 deaths/100 PYs difference), those who had an initial CD4 count < 100 cells/µl (+9.2 deaths/100 PYs difference), and those who were unmarried (+8.0 deaths/100 PYs difference). After adjustment for potential confounders and mediators including CD4 count, a substantially higher mortality rate was predicted among men <30 years old compared to women of the same age, while women ≥50 years old had a mortality rate similar to that of age-matched men, but considerably higher than that predicted among young women (<30 years old). No clinically significant differences were evident with respect to rates of facility transfer or care disengagement between men and women. The main study limitations were the inability to successfully ascertain outcomes in all patients selected for tracing and missing clinical and laboratory data due to the use of medical records. CONCLUSIONS: In this study, we found that among HIV-positive adults newly initiating ART, mortality among men exceeded mortality among women; disparities were most pronounced among young patients. Older women, however, also experienced high mortality. Specific interventions for men and older women at highest mortality risk are needed to improve HIV treatment outcomes.

Participation in adherence clubs and on-time drug pickup among HIV-infected adults in Zambia: A matched-pair cluster randomized trial.

BACKGROUND: Current models of HIV service delivery, with frequent facility visits, have led to facility congestion, patient and healthcare provider dissatisfaction, and suboptimal quality of services and retention in care. The Zambian urban adherence club (AC) is a health service innovation designed to improve on-time drug pickup and retention in HIV care through off-hours facility access and pharmacist-led group drug distribution. Similar models of differentiated service delivery (DSD) have shown promise in South Africa, but observational analyses of these models are prone to bias and confounding. We sought to evaluate the effectiveness and implementation of ACs in Zambia using a more rigorous study design. METHODS AND FINDINGS: Using a matched-pair cluster randomized study design (ClinicalTrials.gov: NCT02776254), 10 clinics were randomized to intervention (5 clinics) or control (5 clinics). At each clinic, between May 19 and October 27, 2016, a systematic random sample was assessed for eligibility (HIV+, age ≥ 14 years, on ART >6 months, not acutely ill, CD4 count not <200 cells/mm3) and willingness to participate in an AC. Clinical and antiretroviral drug pickup data were obtained through the existing electronic medical record. AC meeting attendance data were collected at intervention facilities prospectively through October 28, 2017. The primary outcome was time to first late drug pickup (>7 days late). Intervention effect was estimated using unadjusted Kaplan-Meier survival curves and a Cox proportional hazards model to derive an adjusted hazard ratio (aHR). Medication possession ratio (MPR) and implementation outcomes (adoption, acceptability, appropriateness, feasibility, and fidelity) were additionally evaluated as secondary outcomes. Baseline characteristics were similar between 571 intervention and 489 control participants with respect to median age (42 versus 41 years), sex (62% versus 66% female), median time since ART initiation (4.8 versus 5.0 years), median CD4 count at study enrollment (506 versus 533 cells/mm3), and baseline retention (53% versus 55% with at least 1 late drug pickup in previous 12 months). The rate of late drug pickup was lower in intervention participants compared to control participants (aHR 0.26, 95% CI 0.15-0.45, p < 0.001). Median MPR was 100% in intervention participants compared to 96% in control participants (p < 0.001). Although 18% (683/3,734) of AC group meeting visits were missed, on-time drug pickup (within 7 days) still occurred in 51% (350/683) of these missed visits through alternate means (use of buddy pickup or early return to the facility). Qualitative evaluation suggests that the intervention was acceptable to both patients and providers. While patients embraced the convenience and patient-centeredness of the model, preference for traditional adherence counseling and need for greater human resources influenced intervention appropriateness and feasibility from the provider perspective. The main limitations of this study were the small number of clusters, lack of viral load data, and relatively short follow-up period. CONCLUSIONS: ACs were found to be an effective model of service delivery for reducing late ART drug pickup among HIV-infected adults in Zambia. Drug pickup outside of group meetings was relatively common and underscores the need for DSD models to be flexible and patient-centered if they are to be effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT02776254.

Tailored HIV programmes and universal health coverage.

Improvements in geospatial health data and tailored human immunodeficiency virus (HIV) testing, prevention and treatment have led to greater microtargeting of the HIV response, based on location, risk, clinical status and disease burden. These approaches show promise for achieving control of the HIV epidemic. At the same time, United Nations Member States have committed to achieving broader health and development goals by 2030, including universal health coverage (UHC). HIV epidemic control will facilitate UHC by averting the need to commit ever-increasing resources to HIV services. Yet an overly targeted HIV response could also distort health systems, impede integration and potentially threaten broader health goals. We discuss current approaches to achieving both UHC and HIV epidemic control, noting potential areas of friction between disease-specific microtargeting and integrated health systems, and highlighting opportunities for convergence that could enhance both initiatives. Examples of these programmatic elements that could be better aligned include: improved information systems with unique identifiers to track and monitor individuals across health services and the life course; strengthened subnational data use; more accountable supply chains that supply a broad range of services; and strengthened community-based services and workforces. We argue that the response both to HIV and to broader health threats should use these areas of convergence to increase health systems efficiency and mitigate the harm of any potential decrease in health funding. Further investments in implementation and monitoring of these programme elements will be needed to make progress towards both UHC and HIV epidemic control.

Les améliorations des données sanitaires géospatiales et la personnalisation du dépistage, de la prévention et du traitement du virus de l'immunodéficience humaine (VIH) ont permis de développer le micro-ciblage de la réponse au VIH, en fonction du lieu, du risque, de la situation clinique et de la charge de morbidité. Ces approches sont prometteuses pour lutter contre l'épidémie de VIH. Dans le même temps, les États membres des Nations Unies se sont engagés à atteindre des objectifs plus larges de santé et de développement d'ici 2030, notamment la couverture sanitaire universelle. Cette dernière sera facilitée par la lutte contre l'épidémie de VIH, qui réduira la nécessité de consacrer toujours plus de ressources aux services liés au VIH. Cependant, une réponse au VIH trop ciblée pourrait également distordre les systèmes de santé, empêcher leur intégration et potentiellement nuire aux objectifs de santé plus vastes. Nous abordons ici les approches actuelles en matière de couverture sanitaire universelle et de lutte contre l'épidémie de VIH, en notant les points de friction potentiels entre un micro-ciblage spécifique à certaines maladies et des systèmes de santé intégrés, ainsi que les opportunités de convergence qui pourraient être bénéfiques aux deux initiatives. Parmi les éléments de programmes qui pourraient être mieux coordonnés, nous pouvons citer: l'amélioration des systèmes d'information avec des identifiants uniques permettant de suivre les personnes dans leur parcours de soins et tout au long de leur vie; la plus grande utilisation des données infranationales; la responsabilisation des chaînes d'approvisionnement qui fournissent un grand nombre de services; et le renforcement des services et des intervenants communautaires. Nous soutenons que la réponse au VIH et à d'autres menaces sanitaires devrait exploiter ces domaines de convergence pour accroître l'efficacité des systèmes de santé et atténuer le préjudice d'une éventuelle baisse des fonds alloués à la santé. Il sera nécessaire d'investir davantage dans la mise en œuvre et le suivi de ces éléments de programmes pour avancer, aussi bien vers la couverture sanitaire universelle que dans la lutte contre l'épidémie de VIH.

Las mejoras en los datos geoespaciales de salud y las pruebas, la prevención y el tratamiento adaptados al virus de la inmunodeficiencia humana (VIH) han conducido a una mayor focalización de la respuesta al VIH, basada en la ubicación, el riesgo, el estado clínico y la carga de la enfermedad. Estos enfoques son prometedores para lograr el control de la epidemia del VIH. Al mismo tiempo, los Estados Miembros de las Naciones Unidas se han comprometido a alcanzar objetivos de salud y desarrollo de mayor alcance para 2030, incluida la cobertura universal de salud (universal health coverage, UHC). El control de la epidemia del VIH facilitará la UHC porque evitará la necesidad de comprometer recursos cada vez mayores para los servicios del VIH. Sin embargo, una respuesta al VIH demasiado específica también podría distorsionar los sistemas de salud, impedir la integración y amenazar potencialmente los objetivos de salud de mayor alcance. Se discuten los enfoques actuales para lograr tanto la atención primaria de salud como el control de la epidemia del VIH, se señalan las posibles áreas de fricción entre la focalización específica de la enfermedad y los sistemas integrados de salud, y se destacan las oportunidades de convergencia que podrían mejorar ambas iniciativas. Entre los ejemplos de estos elementos programáticos que podrían alinearse mejor se incluyen: sistemas de información mejorados con identificadores únicos para hacer un seguimiento y monitoreo de las personas a través de los servicios de salud y el curso de la vida; el fortalecimiento del uso de datos a nivel subnacional; cadenas de suministro más responsables que proveen una amplia gama de servicios; y el fortalecimiento de los servicios en la comunidad y las fuerzas de trabajo. Se argumenta que la respuesta tanto al VIH como a las amenazas para la salud en general debe utilizar estas áreas de convergencia para aumentar la eficiencia de los sistemas de salud y mitigar el daño de cualquier posible disminución en la financiación de la salud. Se necesitarán más inversiones en la ejecución y el monitoreo de estos elementos del programa para avanzar tanto en el control de la epidemia de VIH como en la UHC.

How might improved estimates of HIV programme outcomes influence practice? A formative study of evidence, dissemination and response.

BACKGROUND: While HIV programmes have started millions of persons on life-saving antiretroviral therapy in Africa, longitudinal health information systems are frail and, therefore, data about long-term survival is often inaccurate or unknown to HIV programmes. The 'Better Information for Health in Zambia' (BetterInfo) Study - a regional sampling-based survey to assess retention and mortality in HIV programmes in Zambia - found both retention and mortality to be higher than prevailing estimates from national surveillance systems. We sought to understand how Zambian health decision-makers at different health system levels would respond to these new data, with a view to informing research translation. METHODS: We interviewed 25 purposefully sampled health decision-makers from community, facility, district, provincial and national levels. During the interviews, we shared retention and mortality estimates from both routine programme surveillance and those generated by the study. Transcripts were analysed for inductive and deductive themes, the latter drawing on Weiss's framework that policy-makers interpret and apply evidence as 'warning', 'guidance', 'reconceptualisation' or 'mobilisation of support'. FINDINGS: All decision-makers found study findings relevant and important. Decision-makers viewed the underestimates of mortality to be a warning about the veracity and informativeness of routine data systems. Decision-makers felt guided by the findings to improve data monitoring and, acknowledging limitations of routine data, utilised episodic patient tracing to support improved data accuracy. Findings catalysed renewed motivation and mobilisation by national level decision-makers for differentiated models of HIV care to improve patient outcomes and also improved data management systems to better capture patient outcomes. Inductive analysis highlighted a programmatic application data interpretation, in which study findings can influence facility and patient-level decision-making, quality of care and routine data management. CONCLUSIONS: New epidemiological data on patient outcomes were widely seen as informative and relevant and can potentially catalyse health system action such as using evaluations to supplement electronic medical record data to improve HIV programmes. Formative evidence suggests that targeting research dissemination at different levels of the health system will elicit different responses. Researchers supporting the translation of evidence to action should leverage all relevant levels of the health system to facilitate both policy and programmatic action.

Research to improve differentiated HIV service delivery interventions: Learning to learn as we do.

In a Perspective, Elvin Geng and Charles Holmes discuss research on differentiated service delivery in HIV care.

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.

Longitudinal engagement trajectories and risk of death among new ART starters in Zambia: A group-based multi-trajectory analysis.

BACKGROUND: Retention in HIV treatment must be improved to advance the HIV response, but research to characterize gaps in retention has focused on estimates from single time points and population-level averages. These approaches do not assess the engagement patterns of individual patients over time and fail to account for both their dynamic nature and the heterogeneity between patients. We apply group-based trajectory analysis-a special application of latent class analysis to longitudinal data-among new antiretroviral therapy (ART) starters in Zambia to identify groups defined by engagement patterns over time and to assess their association with mortality. METHODS AND FINDINGS: We analyzed a cohort of HIV-infected adults who newly started ART between August 1, 2013, and February 1, 2015, across 64 clinics in Zambia. We performed group-based multi-trajectory analysis to identify subgroups with distinct trajectories in medication possession ratio (MPR, a validated adherence metric based on pharmacy refill data) over the past 3 months and loss to follow-up (LTFU, >90 days late for last visit) among patients with at least 180 days of observation time. We used multinomial logistic regression to identify baseline factors associated with belonging to particular trajectory groups. We obtained Kaplan-Meier estimates with bootstrapped confidence intervals of the cumulative incidence of mortality stratified by trajectory group and performed adjusted Poisson regression to estimate adjusted incidence rate ratios (aIRRs) for mortality by trajectory group. Inverse probability weights were applied to all analyses to account for updated outcomes ascertained from tracing a random subset of patients lost to follow-up as of July 31, 2015. Overall, 38,879 patients (63.3% female, median age 35 years [IQR 29-41], median enrollment CD4 count 280 cells/µl [IQR 146-431]) were included in our cohort. Analyses revealed 6 trajectory groups among the new ART starters: (1) 28.5% of patients demonstrated consistently high adherence and retention; (2) 22.2% showed early nonadherence but consistent retention; (3) 21.6% showed gradually decreasing adherence and retention; (4) 8.6% showed early LTFU with later reengagement; (5) 8.7% had early LTFU without reengagement; and (6) 10.4% had late LTFU without reengagement. Identified groups exhibited large differences in survival: after adjustment, the "early LTFU with reengagement" group (aIRR 3.4 [95% CI 1.2-9.7], p = 0.019), the "early LTFU" group (aIRR 6.4 [95% CI 2.5-16.3], p < 0.001), and the "late LTFU" group (aIRR 4.7 [95% CI 2.0-11.3], p = 0.001) had higher rates of mortality as compared to the group with consistently high adherence/retention. Limitations of this study include using data observed after baseline to identify trajectory groups and to classify patients into these groups, excluding patients who died or transferred within the first 180 days, and the uncertain generalizability of the data to current care standards. CONCLUSIONS: Among new ART starters in Zambia, we observed 6 patient subgroups that demonstrated distinctive engagement trajectories over time and that were associated with marked differences in the subsequent risk of mortality. Further efforts to develop tailored intervention strategies for different types of engagement behaviors, monitor early engagement to identify higher-risk patients, and better understand the determinants of these heterogeneous behaviors can help improve care delivery and survival in this population.

Correction: Retention and viral suppression in a cohort of HIV patients on antiretroviral therapy in Zambia: Regionally representative estimates using a multistage-sampling-based approach.

[This corrects the article DOI: 10.1371/journal.pmed.1002811.].

Retention and viral suppression in a cohort of HIV patients on antiretroviral therapy in Zambia: Regionally representative estimates using a multistage-sampling-based approach.

BACKGROUND: Although the success of HIV treatment programs depends on retention and viral suppression, routine program monitoring of these outcomes may be incomplete. We used data from the national electronic medical record (EMR) system in Zambia to enumerate a large and regionally representative cohort of patients on treatment. We traced a random sample with unknown outcomes (lost to follow-up) to document true care status and HIV RNA levels. METHODS AND FINDINGS: On 31 July 2015, we selected facilities from 4 provinces in 12 joint strata defined by facility type and province with probability proportional to size. In each facility, we enumerated adults with at least 1 clinical encounter after treatment initiation in the previous 24 months. From this cohort, we identified lost-to-follow-up patients (defined as 90 or more days late for their last appointment), selected a random sample, and intensively reviewed their records and traced them via phone calls and in-person visits in the community. In 1 of 4 provinces, we also collected dried blood spots (DBSs) for plasma HIV RNA testing. We used inverse probability weights to incorporate sampling outcomes into Aalen-Johansen and Cox proportional hazards regression to estimate retention and viremia. We used a bias analysis approach to correct for the known inaccuracy of plasma HIV RNA levels obtained from DBSs. From a total of 64 facilities with 165,464 adults on ART, we selected 32 facilities with 104,966 patients, of whom 17,602 (17%) were lost to follow-up: Those lost to follow-up had median age 36 years, 60% were female (N = 11,241), they had median enrollment CD4 count of 220 cells/µl, and 38% had WHO stage 1 clinical disease (N = 10,690). We traced 2,892 (16%) and found updated outcomes for 2,163 (75%): 412 (19%) had died, 836 (39%) were alive and in care at their original clinic, 457 (21%) had transferred to a new clinic, 255 (12%) were alive and out of care, and 203 (9%) were alive but we were unable to determine care status. Estimates using data from the EMR only suggested that 42.7% (95% CI 38.0%-47.1%) of new ART starters and 72.3% (95% CI 71.8%-73.0%) of all ART users were retained at 2 years. After incorporating updated data through tracing, we found that 77.3% (95% CI 70.5%-84.0%) of new initiates and 91.2% (95% CI 90.5%-91.8%) of all ART users were retained (at original clinic or transferred), indicating that routine program data underestimated retention in care markedly. In Lusaka Province, HIV RNA levels greater than or equal to 1,000 copies/ml were present in 18.1% (95% CI 14.0%-22.3%) of patients in care, 71.3% (95% CI 58.2%-84.4%) of lost patients, and 24.7% (95% CI 21.0%-29.3%). The main study limitations were imperfect response rates and the use of self-reported care status. CONCLUSIONS: In this region of Zambia, routine program data underestimated retention, and the point prevalence of unsuppressed HIV RNA was high when lost patients were accounted for. Viremia was prevalent among patients who unofficially transferred: Sustained engagement remains a challenge among HIV patients in Zambia, and targeted sampling is an effective strategy to identify such gaps in the care cascade and monitor programmatic progress.

A Review of Differentiated Service Delivery for HIV Treatment: Effectiveness, Mechanisms, Targeting, and Scale.

PURPOSE OF REVIEW: Differentiated service delivery (DSD) models were initially developed as a means to combat suboptimal long-term retention in HIV care, and to better titrate limited health systems resources to patient needs, primarily in low-income countries. The models themselves are designed to streamline care along the HIV care cascade and range from individual to group-based care and facility to community-based health delivery systems. However, much remains to be understood about how well and for whom DSD models work and whether these models can be scaled, are sustainable, and can reach vulnerable and high-risk populations. Implementation science is tasked with addressing some of these questions through systematic, scientific inquiry. We review the available published evidence on the implementation of DSD and suggest further health systems innovations needed to maximize the public health impact of DSD and future implementation science research directions in this expanding field. RECENT FINDINGS: While early observational data supported the effectiveness of various DSD models, more recently published trials as well as evaluations of national scale-up provide more rigorous evidence for effectiveness and performance at scale. Deeper understanding of the mechanism of effect of various DSD models and generalizability of studies to other countries or contexts remains somewhat limited. Relative implementability of DSD models may differ based on patient preference, logistical complexity of model adoption and maintenance, human resource and pharmacy supply chain needs, and comparative cost-effectiveness. However, few studies to date have evaluated comparative implementation or cost-effectiveness from a health systems perspective. While DSD represents an exciting and promising "next step" in HIV health care delivery, this innovation comes with its own set of implementation challenges. Evidence on the effectiveness of DSD generally supports the use of most DSD models, although it is still unclear which models are most relevant in diverse settings and populations and which are the most cost-effective. Challenges during scale-up highlight the need for accurate differentiation of patients, sustainable inclusion of a new cadre of health care worker (the community health care worker), and substantial strengthening of existing pharmacy supply chains. To maximize the public health impact of DSD, systems need to be patient-centered and adaptive, as well as employ robust quality improvement processes.

Operational characteristics of antiretroviral therapy clinics in Zambia: a time and motion analysis.

BACKGROUND: The mass scale-up of antiretroviral therapy (ART) in Zambia has taken place in the context of limited infrastructure and human resources resulting in many operational side-effects. In this study, we aimed to empirically measure current workload of ART clinic staff and patient wait times and service utilization. METHODS: We conducted time and motion (TAM) studies from both the healthcare worker (HCW) and patient perspectives at 10 ART clinics throughout Zambia. Trained personnel recorded times for consecutive discrete activities based on direct observation of clinical and non-clinical activities performed by counselors, clinical officers, nurses, and pharmacy technicians. For patient TAM, we recruited consenting patients and recorded times of arrival and departure and major ART services utilized. Data from 10 clinics were pooled to evaluate median time per patient spent for each activity and patient duration of stay in the clinic. RESULTS: The percentage of observed clinical time for direct patient interaction (median time per patient encounter) was 43.1% for ART counselors (4 min, interquartile range [IQR] 2-7), 46.1% for nurses (3 min, IQR 2-4), 57.2% for pharmacy technicians (2 min, IQR 1-2), and 78.5% for clinical officers (3 min, IQR 2-5). Patient workloads for HCWs were heaviest between 8 AM and 12 PM with few clinical activities observed after 2 PM. The length of patient visits was inversely associated with arrival time - patients arriving prior to 8 AM spent 61% longer at the clinic than those arriving after 8 AM (277 vs. 171 min). Overall, patients spent 219 min on average for non-clinical visits, and 244 min for clinical visits, but this difference was not significant in rural clinics. In comparison, total time patients spent directly with clinic staff were 9 and 12 min on average for non-clinical and clinical visits. CONCLUSION: Current Zambian ART clinic operations include substantial inefficiencies for both patients and HCWs, with workloads heavily concentrated in the first few hours of clinic opening, limiting HCW and patient interaction time. Use of a differentiated care model may help to redistribute workloads during operational hours and prevent backlogs of patients waiting for hours before clinic opening, which may substantially improve ART delivery in the Zambian context.

Understanding preferences for HIV care and treatment in Zambia: Evidence from a discrete choice experiment among patients who have been lost to follow-up.

BACKGROUND: In public health HIV treatment programs in Africa, long-term retention remains a challenge. A number of improvement strategies exist (e.g., bring services closer to home, reduce visit frequency, expand hours of clinic operation, improve provider attitude), but implementers lack data about which to prioritize when resource constraints preclude implementing all. We used a discrete choice experiment (DCE) to quantify preferences for a number of potential clinic improvements to enhance retention. METHODS AND FINDINGS: We sought a random sample of HIV patients who were lost to follow-up (defined as >90 days late for their last scheduled appointment) from treatment facilities in Lusaka Province, Zambia. Among those contacted, we asked patients to choose between 2 hypothetical clinics in which the following 5 attributes of those facilities were varied: waiting time at the clinic (1, 3, or 5 hours), distance from residence to clinic (5, 10, or 20 km), ART supply given at each refill (1, 3, or 5 months), hours of operation (morning only, morning and afternoon, or morning and Saturday), and staff attitude ("rude" or "nice"). We used mixed-effects logistic regression to estimate relative utility (i.e., preference) for each attribute level. We calculated how much additional waiting time or travel distance patients were willing to accept in order to obtain other desired features of care. Between December 9, 2015 and May 31, 2016, we offered the survey to 385 patients, and 280 participated (average age 35; 60% female). Patients exhibited a strong preference for nice as opposed to rude providers (relative utility of 2.66; 95% CI 1.9-3.42; p < 0.001). In a standard willingness to wait or willingness to travel analysis, patients were willing to wait 19 hours more or travel 45 km farther to see nice rather than rude providers. An alternative analysis, in which trade-offs were constrained to values actually posed to patients in the experiment, suggested that patients were willing to accept a facility located 10 km from home (as opposed to 5) that required 5 hours of waiting per visit (as opposed to 1 hour) and that dispensed 3 months of medications (instead of 5) in order to access nice (as opposed to rude) providers. This study was limited by the fact that attributes included in the experiment may not have captured additional important determinants of preference. CONCLUSIONS: In this study, patients were willing to expend considerable time and effort as well as accept substantial inconvenience in order to access providers with a nice attitude. In addition to service delivery redesign (e.g., differentiated service delivery models), current improvement strategies should also prioritize improving provider attitude and promoting patient centeredness-an area of limited policy attention to date.

Estimated mortality on HIV treatment among active patients and patients lost to follow-up in 4 provinces of Zambia: Findings from a multistage sampling-based survey.

BACKGROUND: Survival represents the single most important indicator of successful HIV treatment. Routine monitoring fails to capture most deaths. As a result, both regional assessments of the impact of HIV services and identification of hotspots for improvement efforts are limited. We sought to assess true mortality on treatment, characterize the extent under-reporting of mortality in routine health information systems in Zambia, and identify drivers of mortality across sites and over time using a multistage, regionally representative sampling approach. METHODS AND FINDINGS: We enumerated all HIV infected adults on antiretroviral therapy (ART) who visited any one of 64 facilities across 4 provinces in Zambia during the 24-month period from 1 August 2013 to 31 July 2015. We identified a probability sample of patients who were lost to follow-up through selecting facilities probability proportional to size and then a simple random sample of lost patients. Outcomes among patients lost to follow-up were incorporated into survival analysis and multivariate regression through probability weights. Of 165,464 individuals (64% female, median age 39 years (IQR 33-46), median CD4 201 cells/mm3 (IQR 111-312), the 2-year cumulative incidence of mortality increased from 1.9% (95% CI 1.7%-2.0%) to a corrected rate of 7.0% (95% CI 5.7%-8.4%) (all ART users) and from 2.1% (95% CI 1.8%-2.4%) to 8.3% (95% CI 6.1%-10.7%) (new ART users). Revised provincial mortality rates ranged from 3-9 times higher than naïve rates for new ART users and were lowest in Lusaka Province (4.6 per 100 person-years) and highest in Western Province (8.7 per 100 person-years) after correction. Corrected mortality rates varied markedly by clinic, with an IQR of 3.5 to 7.5 deaths per 100 person-years and a high of 13.4 deaths per 100 person-years among new ART users, even after adjustment for clinical (e.g., pretherapy CD4) and contextual (e.g., province and clinic size) factors. Mortality rates (all ART users) were highest year 1 after treatment at 4.6/100 person-years (95% CI 3.9-5.5), 2.9/100 person-years (95% CI 2.1-3.9) in year 2, and approximately 1.6% per year through 8 years on treatment. In multivariate analysis, patient-level factors including male sex and pretherapy CD4 levels and WHO stage were associated with higher mortality among new ART users, while male sex and HIV disclosure were associated with mortality among all ART users. In both cases, being late (>14 days late for appointment) or lost (>90 days late for an appointment) was associated with deaths. We were unable to ascertain the vital status of about one-quarter of those lost and selected for tracing and did not adjudicate causes of death. CONCLUSIONS: HIV treatment in Zambia is not optimally effective. The high and sustained mortality rates and marked under-reporting of mortality at the provincial-level and unexplained heterogeneity between regions and sites suggest opportunities for the use of corrected mortality rates for quality improvement. A regionally representative sampling-based approach can bring gaps and opportunities for programs into clear epidemiological focus for local and global decision makers.

Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia.

BACKGROUND: Although randomized trials have established the clinical efficacy of treating all persons living with HIV (PLWHs), expanding treatment eligibility in the real world may have additional behavioral effects (e.g., changes in retention) or lead to unintended consequences (e.g., crowding out sicker patients owing to increased patient volume). Using a regression discontinuity design, we sought to assess the effects of a previous change to Zambia's HIV treatment guidelines increasing the threshold for treatment eligibility from 350 to 500 cells/µL to anticipate effects of current global efforts to treat all PLWHs. METHODS AND FINDINGS: We analyzed antiretroviral therapy (ART)-naïve adults who newly enrolled in HIV care in a network of 64 clinics operated by the Zambian Ministry of Health and supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). Patients were restricted to those enrolling in a narrow window around the April 1, 2014 change to Zambian HIV treatment guidelines that raised the CD4 threshold for treatment from 350 to 500 cells/µL (i.e., August 1, 2013, to November 1, 2014). Clinical and sociodemographic data were obtained from an electronic medical record system used in routine care. We used a regression discontinuity design to estimate the effects of this change in treatment eligibility on ART initiation within 3 months of enrollment, retention in care at 6 months (defined as clinic attendance between 3 and 9 months after enrollment), and a composite of both ART initiation by 3 months and retention in care at 6 months in all new enrollees. We also performed an instrumental variable (IV) analysis to quantify the effect of actually initiating ART because of this guideline change on retention. Overall, 34,857 ART-naïve patients (39.1% male, median age 34 years [IQR 28-41], median CD4 268 cells/µL [IQR 134-430]) newly enrolled in HIV care during this period; 23,036 were analyzed after excluding patients around the threshold to allow for clinic-to-clinic variations in actual guideline uptake. In all newly enrolling patients, expanding the CD4 threshold for treatment from 350 to 500 cells/µL was associated with a 13.6% absolute increase in ART initiation within 3 months of enrollment (95% CI, 11.1%-16.2%), a 4.1% absolute increase in retention at 6 months (95% CI, 1.6%-6.7%), and a 10.8% absolute increase in the percentage of patients who initiated ART by 3 months and were retained at six months (95% CI, 8.1%-13.5%). These effects were greatest in patients who would have become newly eligible for ART with the change in guidelines: a 43.7% increase in ART initiation by 3 months (95% CI, 37.5%-49.9%), 13.6% increase in retention at six months (95% CI, 7.3%-20.0%), and a 35.5% increase in the percentage of patients on ART at 3 months and still in care at 6 months [95% CI, 29.2%-41.9%). We did not observe decreases in ART initiation or retention in patients not directly targeted by the guideline change. An IV analysis found that initiating ART in response to the guideline change led to a 37.9% (95% CI, 28.8%-46.9%) absolute increase in retention in care. Limitations of this study include uncertain generalizability under newer models of care, lack of laboratory data (e.g., viral load), inability to account for earlier stages in the HIV care cascade (e.g., HIV testing and linkage), and potential for misclassification of eligibility status or outcome. CONCLUSIONS: In this study, guidelines raising the CD4 threshold for treatment from 350 to 500 cells/µL were associated with a rapid rise in ART initiation as well as enhanced retention among newly treatment-eligible patients, without negatively impacting patients with lower CD4 levels. These data suggest that health systems in Zambia and other high-prevalence settings could substantially enhance engagement even among those with high CD4 levels (i.e., above 500 cells/µL) by expanding treatment without undermining existing care standards.