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.

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.

A clinical algorithm for same-day HIV treatment initiation in settings with high TB symptom prevalence in South Africa: The SLATE II individually randomized clinical trial.

BACKGROUND: Many countries encourage same-day initiation of antiretroviral therapy (ART), but evidence on eligibility for same-day initiation, how best to implement it, and its impact on outcomes remains scarce. Building on the Simplified Algorithm for Treatment Eligibility (SLATE) I trial, in which nearly half of participants were ineligible for same-day initiation mainly because of TB symptoms, the study evaluated the revised SLATE II algorithm, which allowed same-day initiation for patients with mild TB symptoms and other less serious reasons for delay. METHODS AND FINDINGS: SLATE II was a nonblinded, 1:1 individually randomized pragmatic trial at three primary healthcare clinics in Johannesburg, South Africa. It randomized adult patients presenting for an HIV test or any HIV care but not yet on ART. Intervention arm patients were assessed with a symptom screen, medical history, brief physical examination, and readiness questionnaire to distinguish between patients eligible for immediate ART dispensing and those requiring further care before initiation. Standard arm patients received usual care. Follow-up was by review of routine clinic records. Primary outcomes were (1) ART initiation in ≤7 days and (2) ART initiation in ≤28 days and retention in care at 8 months (composite outcome). From 14 March to 18 September 2018, 593 adult HIV+, nonpregnant patients were enrolled (median interquartile range [IQR] age 35 [29-43]; 63% (n = 373) female; median CD4 count 293 [133-487]). Half of study patients (n = 295) presented with TB symptoms, whereas only 13 (4%) standard arm and 7 (2%) intervention arm patients tested positive for TB disease. Among 140 intervention arm patients with TB symptoms, 72% were eligible for same-day initiation. Initiation was higher in the intervention (n = 296) versus standard arm (n = 297) by 7 days (91% versus 68%; risk difference [RD] 23% [95% confidence interval (CI) 17%-29%]) and 28 days (94% versus 82%; RD 12% [7%-17%]) after enrollment. In total, 87% of intervention and 38% of standard arm patients initiated on the same day. By 8 months after study enrollment, 74% (220/296) of intervention and 59% (175/297) of standard arm patients had both initiated ART in ≤28 days and been retained in care (RD 15% [7%-23%]). Among the 41% of participants with viral load results available, suppression was 90% in the standard arm and 92% in the intervention arm among patients initiated in ≤28 days. No ART-associated adverse events were reported after initiation; two intervention and four standard arm patients were reported to have died during passive follow-up. Limitations of the study included limited geographic generalizability, exclusion of patients too sick to consent, fluctuations in procedures in the standard arm over the course of the study, high fidelity to the trial protocol by study staff, and the possibility of overestimating loss to follow-up due to data constraints. CONCLUSIONS: More than 85% of patients presenting for HIV testing or care, including those newly diagnosed, were eligible and ready for same-day initiation under the SLATE II algorithm. The algorithm increased initiation within 7 days without appearing to compromise retention and viral suppression at 8 months, offering a practical and acceptable approach that can be widely and immediately utilized by existing providers. TRIAL REGISTRATION: Clinicaltrials.gov NCT03315013, registered 19 October 2017. First participant enrolled 14 March 2018.

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.

Emerging priorities for HIV service delivery.

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

Risk scores for predicting early antiretroviral therapy mortality in sub-Saharan Africa to inform who needs intensification of care: a derivation and external validation cohort study.

BACKGROUND: Clinical scores to determine early (6-month) antiretroviral therapy (ART) mortality risk have not been developed for sub-Saharan Africa (SSA), home to 70% of people living with HIV. In the absence of validated scores, WHO eligibility criteria (EC) for ART care intensification are CD4 < 200/µL or WHO stage III/IV. METHODS: We used Botswana XPRES trial data for adult ART enrollees to develop CD4-independent and CD4-dependent multivariable prognostic models for 6-month mortality. Scores were derived by rescaling coefficients. Scores were developed using the first 50% of XPRES ART enrollees, and their accuracy validated internally and externally using South African TB Fast Track (TBFT) trial data. Predictive accuracy was compared between scores and WHO EC. RESULTS: Among 5553 XPRES enrollees, 2838 were included in the derivation dataset; 68% were female and 83 (3%) died by 6 months. Among 1077 TBFT ART enrollees, 55% were female and 6% died by 6 months. Factors predictive of 6-month mortality in the derivation dataset at p < 0.01 and selected for the CD4-independent score included male gender (2 points), ≥ 1 WHO tuberculosis symptom (2 points), WHO stage III/IV (2 points), severe anemia (hemoglobin < 8 g/dL) (3 points), and temperature > 37.5 °C (2 points). The same variables plus CD4 < 200/µL (1 point) were included in the CD4-dependent score. Among XPRES enrollees, a CD4-independent score of ≥ 4 would provide 86% sensitivity and 66% specificity, whereas WHO EC would provide 83% sensitivity and 58% specificity. If WHO stage alone was used, sensitivity was 48% and specificity 89%. Among TBFT enrollees, the CD4-independent score of ≥ 4 would provide 95% sensitivity and 27% specificity, whereas WHO EC would provide 100% sensitivity but 0% specificity. Accuracy was similar between CD4-independent and CD4-dependent scores. Categorizing CD4-independent scores into low (< 4), moderate (4-6), and high risk (≥ 7) gave 6-month mortality of 1%, 4%, and 17% for XPRES and 1%, 5%, and 30% for TBFT enrollees. CONCLUSIONS: Sensitivity of the CD4-independent score was nearly twice that of WHO stage in predicting 6-month mortality and could be used in settings lacking CD4 testing to inform ART care intensification. The CD4-dependent score improved specificity versus WHO EC. Both scores should be considered for scale-up in SSA.

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.

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.

Effectiveness of a combination strategy for linkage and retention in adult HIV care in Swaziland: The Link4Health cluster randomized trial.

BACKGROUND: Gaps in the HIV care continuum contribute to poor health outcomes and increase HIV transmission. A combination of interventions targeting multiple steps in the continuum is needed to achieve the full beneficial impact of HIV treatment. METHODS AND FINDINGS: Link4Health, a cluster-randomized controlled trial, evaluated the effectiveness of a combination intervention strategy (CIS) versus the standard of care (SOC) on the primary outcome of linkage to care within 1 month plus retention in care at 12 months after HIV-positive testing. Ten clusters of HIV clinics in Swaziland were randomized 1:1 to CIS versus SOC. The CIS included point-of-care CD4+ testing at the time of an HIV-positive test, accelerated antiretroviral therapy (ART) initiation for treatment-eligible participants, mobile phone appointment reminders, health educational packages, and noncash financial incentives. Secondary outcomes included each component of the primary outcome, mean time to linkage, assessment for ART eligibility, ART initiation and time to ART initiation, viral suppression defined as HIV-1 RNA < 1,000 copies/mL at 12 months after HIV testing among patients on ART ≥6 months, and loss to follow-up and death at 12 months after HIV testing. A total of 2,197 adults aged ≥18 years, newly tested HIV positive, were enrolled from 19 August 2013 to 21 November 2014 (1,096 CIS arm; 1,101 SOC arm) and followed for 12 months. The median participant age was 31 years (IQR 26-39), and 59% were women. In an intention-to-treat analysis, 64% (705/1,096) of participants at the CIS sites achieved the primary outcome versus 43% (477/1,101) at the SOC sites (adjusted relative risk [RR] 1.52, 95% CI 1.19-1.96, p = 0.002). Participants in the CIS arm versus the SOC arm had the following secondary outcomes: linkage to care regardless of retention at 12 months (RR 1.08, 95% CI 0.97-1.21, p = 0.13), mean time to linkage (2.5 days versus 7.5 days, p = 0.189), retention in care at 12 months regardless of time to linkage (RR 1.48, 95% CI 1.18-1.86, p = 0.002), assessment for ART eligibility (RR 1.20, 95% CI 1.07-1.34, p = 0.004), ART initiation (RR 1.16, 95% CI 0.96-1.40, p = 0.12), mean time to ART initiation from time of HIV testing (7 days versus 14 days, p < 0.001), viral suppression among those on ART for ≥6 months (RR 0.97, 95% CI 0.88-1.07, p = 0.55), loss to follow-up at 12 months after HIV testing (RR 0.56, 95% CI 0.40-0.79, p = 0.002), and death (N = 78) within 12 months of HIV testing (RR 0.80, 95% CI 0.46-1.35, p = 0.41). Limitations of this study include a small number of clusters and the inability to evaluate the incremental effectiveness of individual components of the combination strategy. CONCLUSIONS: A combination strategy inclusive of 5 evidence-based interventions aimed at multiple steps in the HIV care continuum was associated with significant increase in linkage to care plus 12-month retention. This strategy offers promise of enhanced outcomes for HIV-positive patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01904994.

Accelerating the Uptake and Timing of Antiretroviral Therapy Initiation in Sub-Saharan Africa: An Operations Research Agenda.

Sydney Rosen and colleagues describe an operations research agenda to accelerating uptake of HIV treatment initiation.

Lower Levels of Antiretroviral Therapy Enrollment Among Men with HIV Compared with Women - 12 Countries, 2002-2013.

Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(†) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.

Antiretroviral therapy enrollment characteristics and outcomes among HIV-infected adolescents and young adults compared with older adults--seven African countries, 2004-2013.

Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by age at enrollment: adolescents and young adults (aged 15-24 years), middle-aged adults (aged 25-49 years), and older adults (aged ≥50 years). Enrollees aged 15-24 years were predominantly female (81%-92%), commonly pregnant (3%-32% of females), unmarried (54%-73%), and, in four countries with employment data, unemployed (53%-86%). In comparison, older adults were more likely to be male (p<0.001), employed (p<0.001), and married, (p<0.05 in five countries). Compared with older adults, adolescents and young adults had higher LTFU rates in all seven countries, reaching statistical significance in three countries in crude and multivariable analyses. Evidence-based interventions to reduce LTFU for adolescent and young adult ART enrollees could help reduce mortality and HIV incidence in this age group.

Reasons for disengagement from antiretroviral care in the era of "Treat All" in low- or middle-income countries: a systematic review.

INTRODUCTION: Disengagement from antiretroviral therapy (ART) care is an important reason why people living with HIV do not achieve viral load suppression become unwell. METHODS: We searched two databases and conference abstracts from January 2015 to December 2022 for studies which reported reasons for disengagement from ART care. We included quantitative (mainly surveys) and qualitative (in-depth interviews or focus groups) studies conducted after "treat all" or "Option B+" policy adoption. We used an inductive approach to categorize reasons: we report how often reasons were reported in studies and developed a conceptual framework for reasons. RESULTS: We identified 21 studies which reported reasons for disengaging from ART care in the "Treat All" era, mostly in African countries: six studies in the general population of persons living with HIV, nine in pregnant or postpartum women and six in selected populations (one each in people who use drugs, isolated indigenous communities, men, women, adolescents and men who have sex with men). Reasons reported were: side effects or other antiretroviral tablet issues (15 studies); lack of perceived benefit of ART (13 studies); psychological, mental health or drug use (13 studies); concerns about stigma or confidentiality (14 studies); lack of social or family support (12 studies); socio-economic reasons (16 studies); health facility-related reasons (11 studies); and acute proximal events such as unexpected mobility (12 studies). The most common reasons for disengagement were unexpected events, socio-economic reasons, ART side effects or lack of perceived benefit of ART. Conceptually, studies described underlying vulnerability factors (individual, interpersonal, structural and healthcare) but that often unexpected proximal events (e.g. unanticipated mobility) acted as the trigger for disengagement to occur. DISCUSSION: People disengage from ART care for individual, interpersonal, structural and healthcare reasons, and these reasons overlap and interact with each other. While HIV programmes cannot predict and address all events that may lead to disengagement, an approach that recognizes that such shocks will happen could help. CONCLUSIONS: Health services should focus on ways to encourage clients to engage with care by making ART services welcoming, person-centred and more flexible alongside offering adherence interventions, such as counselling and peer support.

Potential cost-effectiveness of community availability of tenofovir, lamivudine, and dolutegravir for HIV prevention and treatment in east, central, southern, and west Africa: a modelling analysis.

BACKGROUND: Post-exposure prophylaxis (PEP) offers protection from HIV after condomless sex, but is not widely available in a timely manner in east, central, southern, and west Africa. To inform the potential pilot implementation of such an approach, we modelled the effect and cost-effectiveness of making PEP consisting of tenofovir, lamivudine, and dolutegravir (TLD) freely and locally available in communities without prescription, with the aim of enabling PEP use within 24 h of condomless sex. Free community availability of TLD (referred to as community TLD) might also result in some use of TLD as pre-exposure prophylaxis (PrEP) and as antiretroviral therapy for people living with HIV. METHODS: Using an existing individual-based model (HIV Synthesis), we explicitly modelled the potential positive and negative effects of community TLD. Through the sampling of parameter values we created 1000 setting-scenarios, reflecting the uncertainty in assumptions and a range of settings similar to those seen in east, central, southern, and west Africa (with a median HIV prevalence of 14·8% in women and 8·1% in men). For each setting scenario, we considered the effects of community TLD. TLD PEP was assumed to have at least 90% efficacy in preventing HIV infection after condomless sex with a person living with HIV. FINDINGS: The modelled effects of community TLD availability based on an assumed high uptake of TLD resulted in a mean reduction in incidence of 31% (90% range over setting scenarios, 6% increase to 57% decrease) over 20 years, with an HIV incidence reduction over 50 years in 91% of the 1000 setting scenarios, deaths averted in 55% of scenarios, reduction in costs in 92% of scenarios, and disability-adjusted life-years averted in 64% of scenarios with community TLD. Community TLD was cost-effective in 90% of setting scenarios and cost-saving (with disability-adjusted life-years averted) in 58% of scenarios. When only examining setting scenarios in which there was lower uptake of community TLD, community TLD is cost-effective in 92% of setting scenarios. INTERPRETATION: The introduction of community TLD, enabling greater PEP access, is a promising approach to consider further in pilot implementation projects. FUNDING: Bill & Melinda Gates Foundation to the HIV Modelling Consortium.

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.

Expanding the Vision for Differentiated Service Delivery: A Call for More Inclusive and Truly Patient-Centered Care for People Living With HIV.

BACKGROUND: Simplifying antiretroviral therapy for clinically stable people living with HIV (PLHIV) is important but insufficient to meet their health care needs, including prevention and treatment of tuberculosis and noncommunicable diseases, routine primary care, and family planning. Integrating these services into differentiated service delivery (DSD) platforms is a promising avenue to achieve such coverage. We propose a transition from an HIV-focused "DSD 1.0" to a patient-centered "DSD 2.0" that is inclusive of additional chronic care services for PLHIV. DISCUSSION: The lack of coordination between HIV programs and these critical services puts a burden on both PLHIV and health systems. For individual patients, fractionated services increase cost and time, diminish the actual and perceived quality of care, and increase the risk that they will disengage from health care altogether. The burden on the health system is one of inefficiency and suboptimal outcomes resulting from the parallel systems required to manage multiple vertical programs. CONCLUSIONS: DSD 2.0 provides an opportunity for the HIV and Universal Health Coverage agendas-which can seem to be at odds-to achieve greater collective impact for patients and health systems by integrating strong vertical HIV, tuberculosis and family planning programs, and relatively weaker noncommunicable disease programs. Increasing coordination of care for PLHIV will increase the likelihood of achieving and sustaining UNAIDS' goals of retention on antiretroviral therapy and viral suppression. Eventually, this shift to DSD 2.0 for PLHIV could evolve to a more person-centered vision of chronic care services that would also serve the general population.