Person-centred interventions to improve patient-provider relationships for HIV services in low- and middle-income countries: a systematic review.

INTRODUCTION: Person-centred care (PCC) has been recognized as a critical element in delivering quality and responsive health services. The patient-provider relationship, conceptualized at the core of PCC in multiple models, remains largely unexamined in HIV care. We conducted a systematic review to better understand the types of PCC interventions implemented to improve patient-provider interactions and how these interventions have improved HIV care continuum outcomes and person-reported outcomes (PROs) among people living with HIV in low- and middle-income countries. METHODS: We searched databases, conference proceedings and conducted manual targeted searches to identify randomized trials and observational studies published up to January 2023. The PCC search terms were guided by the Integrative Model of Patient-Centeredness by Scholl. We included person-centred interventions aiming to enhance the patient-provider interactions. We included HIV care continuum outcomes and PROs. RESULTS: We included 28 unique studies: 18 (64.3%) were quantitative, eight (28.6.%) were mixed methods and two (7.1%) were qualitative. Within PCC patient-provider interventions, we inductively identified five categories of PCC interventions: (1) providing friendly and welcoming services; (2) patient empowerment and improved communication skills (e.g. supporting patient-led skills such as health literacy and approaches when communicating with a provider); (3) improved individualized counselling and patient-centred communication (e.g. supporting provider skills such as training on motivational interviewing); (4) audit and feedback; and (5) provider sensitisation to patient experiences and identities. Among the included studies with a comparison arm and effect size reported, 62.5% reported a significant positive effect of the intervention on at least one HIV care continuum outcome, and 100% reported a positive effect of the intervention on at least one of the included PROs. DISCUSSION: Among published HIV PCC interventions, there is heterogeneity in the components of PCC addressed, the actors involved and the expected outcomes. While results are also heterogeneous across clinical and PROs, there is more evidence for significant improvement in PROs. Further research is necessary to better understand the clinical implications of PCC, with fewer studies measuring linkage or long-term retention or viral suppression. CONCLUSIONS: Improved understanding of PCC domains, mechanisms and consistency of measurement will advance PCC research and implementation.

HIV epidemiology, prevention, treatment, and implementation strategies for public health.

The global HIV response has made tremendous progress but is entering a new phase with additional challenges. Scientific innovations have led to multiple safe, effective, and durable options for treatment and prevention, and long-acting formulations for 2-monthly and 6-monthly dosing are becoming available with even longer dosing intervals possible on the horizon. The scientific agenda for HIV cure and remission strategies is moving forward but faces uncertain thresholds for success and acceptability. Nonetheless, innovations in prevention and treatment have often failed to reach large segments of the global population (eg, key and marginalised populations), and these major disparities in access and uptake at multiple levels have caused progress to fall short of their potential to affect public health. Moving forward, sharper epidemiologic tools based on longitudinal, person-centred data are needed to more accurately characterise remaining gaps and guide continued progress against the HIV epidemic. We should also increase prioritisation of strategies that address socio-behavioural challenges and can lead to effective and equitable implementation of existing interventions with high levels of quality that better match individual needs. We review HIV epidemiologic trends; advances in HIV prevention, treatment, and care delivery; and discuss emerging challenges for ending the HIV epidemic over the next decade that are relevant for general practitioners and others involved in HIV care.

Instrumental variables for implementation science: exploring context-dependent causal pathways between implementation strategies and evidence-based interventions.

BACKGROUND: The impact of both implementation strategies (IS) and evidence-based interventions (EBI) can vary across contexts, and a better understanding of how and why this occurs presents fundamental but challenging questions that implementation science as a field will need to grapple with. We use causal epidemiologic methods to explore the mechanisms of why sharp distinctions between implementation strategies (IS) and efficacy of an evidence-based intervention (EBI) may fail to recognize that the effect of an EBI can be deeply intertwined and dependent on the context of the IS leading to its uptake. METHODS: We explore the use of instrumental variable (IV) analyses as a critical tool for implementation science methods to isolate three relevant quantities within the same intervention context when exposure to an implementation strategy is random: (1) the effect of an IS on implementation outcomes (e.g., uptake), (2) effect of EBI uptake on patient outcomes, and (3) overall effectiveness of the IS (i.e., ~ implementation*efficacy). We discuss the mechanisms by which an implementation strategy can alter the context, and therefore effect, of an EBI using the underlying IV assumptions. We illustrate these concepts using examples of the implementation of new ART initiation guidelines in Zambia and community-based masking programs in Bangladesh. RESULTS: Causal questions relevant to implementation science are answered at each stage of an IV analysis. The first stage assesses the effect of the IS (e.g., new guidelines) on EBI uptake (e.g., same-day treatment initiation). The second stage leverages the IS as an IV to estimate the complier average causal effect (CACE) of the EBI on patient outcomes (e.g., effect of same-day treatment initiation on viral suppression). The underlying assumptions of CACE formalize that the causal effect of EBI may differ in the context of a different IS because (1) the mechanisms by which individuals uptake an intervention may differ and (2) the subgroup of individuals who take up an EBI may differ. IV methods thus provide a conceptual framework for how IS and EBIs are linked and that the IS itself needs to be considered a critical contextual determinant. Moreover, it also provides rigorous methodologic tools to isolate the effect of an IS, EBI, and combined effect of the IS and EBI. DISCUSSION: Leveraging IV methods when exposure to an implementation strategy is random helps to conceptualize the context-dependent nature of implementation strategies, EBIs, and patient outcomes. IV methods formalize that the causal effect of an EBI may be specific to the context of the implementation strategy used to promote uptake. This integration of implementation science concepts and theory with rigorous causal epidemiologic methods yields novel insights and provides important tools for exploring the next generation of questions related to mechanisms and context in implementation science.

Leveraging CD4 Cell Count at Entry Into Care to Monitor Success of Human Immunodeficiency Virus Prevention, Treatment, and Public Health Programming in the Greater St Louis Area Between 2017 and 2020.

CD4 cell count at entry into human immunodeficiency virus (HIV) care is a useful indicator of success of multiple steps in HIV public health programming. We demonstrate that CD4 cell count at care initiation was stable in St Louis between 2017 and 2019 but declined in 2020. Missouri efforts in the Ending the HIV Epidemic plan should focus on rapidly identifying individuals with undiagnosed HIV infection.

Patterns of person-centred communications in public HIV clinics: a latent class analysis using the Roter interaction analysis system.

INTRODUCTION: Poor client-provider communication is a critical barrier to long-term retention in care among people living with HIV. However, standardized assessments of this key metric are limited in Africa. We used the Roter Interaction Analysis System (RIAS) to quantitatively characterize patterns of person-centred communication (PCC) behaviours in Zambia. METHODS: We enrolled pairs of people living with HIV making routine HIV follow-up visit and their providers at 24 Ministry of Health-facilities supported by the Centre for Infectious Disease Research in Zambia in Lusaka province between August 2019 and November 2021. Client-provider encounters were audio-recorded and coded using RIAS by trained research staff. We performed latent class analysis to identify interactions with distinctive patterns of provider PCC behaviours (i.e. rapport building, person-centred counselling, PCC micropractices [e.g. brief empathy statements], assessing barriers to care, shared decision-making and leveraging discretionary power) and compared their distribution across client, provider, interaction and facility characteristics. RESULTS: We enrolled 478 people living with HIV and 139 providers (14% nurses, 73.6% clinical officers, 12.3% were medical officers). We identified four distinct profiles: (1) "Medically Oriented Interaction, Minimal PCC Behaviours" (47.6% of interactions) was characterized by medical discussion, minimal psychosocial/non-medical talk and low use of PCC behaviours; (2) "Balanced Medical/Non-medical Interaction, Low PCC Behaviours" (21.0%) was characterized by medical and non-medical discussion but limited use of other PCC behaviours; (3) "Medically Oriented Interaction, Good PCC Behaviours" (23.9%) was characterized by medically oriented discussion, more information-giving and increased use of PCC behaviours; and (4) "Highly person-centred Interaction" (7.5%) was characterized by both balanced medical/non-medical focus and the highest use of PCC behaviours. Nurse interactions were more likely to be characterized by more PCC behaviours (i.e. Class 3 or 4) (44.8%), followed by medical officers (33.9%) and clinical officers (27.3%) (p = 0.031). Longer interactions were also more likely to integrate more PCC behaviours (p < 0.001). CONCLUSIONS: PCC behaviours are relatively uncommon in HIV care in Zambia, and often limited to brief rapport-building statements and PCC micropractices. Strengthening PCC, such as shared decision-making and leveraging discretionary power to better accommodate client needs and preferences, may be an important strategy for improving the quality in HIV treatment programmes.

Provider perspectives on patient-centredness: participatory formative research and rapid analysis methods to inform the design and implementation of a facility-based HIV care improvement intervention in Zambia.

INTRODUCTION: Implementation of patient-centred care (PCC) practices in HIV treatment depends on healthcare workers' (HCWs) perceptions of the acceptability, appropriateness and feasibility of such practices (e.g. use of intentional, metric-driven activities to improve patient experiences). METHODS: We applied rapid, rigorous formative research methods to refine a PCC intervention for future trial. In 2018, we conducted focus group discussions (FGDs) with 46 HCWs purposefully selected from two pilot sites. We elicited HCW perceptions of HIV service delivery, HCW motivation and perceived value of patient experience measures intended to improve PCC. FGDs utilized participatory methods to understand HCW responses to patient-reported care engagement challenges and Scholl's PCC Framework principles (e.g. seeing a patient as a unique person), enablers (e.g. care coordination) and activities (e.g. patient involvement). Our rapid analysis used analytic memos, thematic analysis, research team debriefs and HCW feedback to inform time-sensitive trial implementation. RESULTS: While HCWs nearly universally identified with and supported principles of PCC in both facilities, they raised practical barriers given the practice environment. HCWs described motivation to help patients, attached value to seeing positive health outcomes and the importance of teamwork. However, HCWs reported challenges with enablers needed to deliver PCC. HCWs cited a work culture characterized by differential power dynamics between cadres and departments restricting HCW autonomy and resource access. Barriers included inflexibility in accommodating individual patient needs due to high patient volumes, limited human resources, laboratory capacity, infrastructure and skills translating patient perspectives into practice. HCW motivation was negatively influenced by encounters with "difficult patients," and feeling "unappreciated" by management, resulting in cognitive dissonance between HCW beliefs and behaviours. However, the enactment of PCC values also occurred. Results suggested that PCC interventions should reduce practice barriers, highlighting the value of mentors who could help HCWs dynamically engage with health system constraints, to facilitate PCC. CONCLUSIONS: While HCWs perceived PCC principles as acceptable, they did not think it universally appropriate or feasible given the practice environment. Participatory and rapid methods provided timely insight that PCC interventions must provide clear and effective systems enabling PCC activities by measuring and mitigating relational and organizational constraints amenable to change such as inter-cadre coordination.

Comparison of patient exit interviews with unannounced standardised patients for assessing HIV service delivery in Zambia: a study nested within a cluster randomised trial.

OBJECTIVES: To compare unannounced standardised patient approach (eg, mystery clients) with typical exit interviews for assessing patient experiences in HIV care (eg, unfriendly providers, long waiting times). We hypothesise standardised patients would report more negative experiences than typical exit interviews affected by social desirability bias. SETTING: Cross-sectional surveys in 16 government-operated HIV primary care clinics in Lusaka, Zambia providing antiretroviral therapy (ART). PARTICIPANTS: 3526 participants aged ≥18 years receiving ART participated in the exit surveys between August 2019 and November 2021. INTERVENTION: Systematic sample (every nth file) of patients in clinic waiting area willing to be trained received pre-visit training and post-visit interviews. Providers were unaware of trained patients. OUTCOME MEASURES: We compared patient experience among patients who received brief training prior to their care visit (explaining each patient experience construct in the exit survey, being anonymous, without manipulating behaviour) with those who did not undergo training on the survey prior to their visit. RESULTS: Among 3526 participants who participated in exit surveys, 2415 were untrained (56% female, median age 40 (IQR: 32-47)) and 1111 were trained (50% female, median age 37 (IQR: 31-45)). Compared with untrained, trained patients were more likely to report a negative care experience overall (adjusted prevalence ratio (aPR) for aggregate sum score: 1.64 (95% CI: 1.39 to 1.94)), with a greater proportion reporting feeling unwelcome by providers (aPR: 1.71 (95% CI: 1.20 to 2.44)) and witnessing providers behaving rude (aPR: 2.28 (95% CI: 1.63 to 3.19)). CONCLUSION: Trained patients were more likely to identify suboptimal care. They may have understood the items solicited better or felt empowered to be more critical. We trained existing patients, unlike studies that use 'standardised patients' drawn from outside the patient population. This low-cost strategy could improve patient-centred service delivery elsewhere. TRIAL REGISTRATION NUMBER: Assessment was nested within a parent study; www.pactr.org registered the parent study (PACTR202101847907585).

Correction: Evaluation of kidney function among people living with HIV initiating antiretroviral therapy in Zambia.

[This corrects the article DOI: 10.1371/journal.pgph.0000124.].

Cross-sectional study to assess depression among healthcare workers in Lusaka, Zambia during the COVID-19 pandemic.

OBJECTIVES: We sought to assess depression among healthcare workers (HCWs) in the context of COVID-19 in Lusaka Province, Zambia. DESIGN: This cross-sectional study is nested within a larger study, the Person-Centred Public Health for HIV Treatment in Zambia (PCPH), a cluster-randomised trial to assess HIV care and outcomes. SETTING: The research was conducted in 24 government-run health facilities from 11 August to 15 October 2020 during the first wave of the COVID-19 pandemic in Lusaka, Zambia. PARTICIPANTS: We used convenience sampling to recruit HCW participants who were previously enrolled in the PCPH study, had more than 6 months' experience working at the facility and were voluntarily willing to participate. PRIMARY OUTCOME MEASURES: We implemented the well-validated 9-question Patient Health Questionnaire (PHQ-9) to assess HCW depression. We used mixed-effects, adjusted Poisson regression to estimate the marginal probability of HCWs experiencing depression that may warrant intervention (PHQ-9 score ≥5) by healthcare facility. RESULTS: We collected PHQ-9 survey responses from 713 professional and lay HCWs. Overall, 334 (46.8%, 95% CI 43.1%, 50.6%) HCWs recorded a PHQ-9 score ≥5, indicating the need for further assessment and potential intervention for depression. We identified significant heterogeneity across facilities and observed a greater proportion of HCWs with symptoms of depression in facilities providing COVID-19 testing and treatment services. CONCLUSIONS: Depression may be a concern for a large proportion of HCWs in Zambia. Further work to understand the magnitude and aetiologies of depression among HCWs in the public sector is needed to design effective prevention and treatment interventions to meet the needs for mental health support and to minimise poor health outcomes.

On-the-Go Adaptation of Implementation Approaches and Strategies in Health: Emerging Perspectives and Research Opportunities.

In many cases, implementation approaches (composed of one or more strategies) may need to change over time to work optimally. We use a literature review to inform a mechanistic analysis of such on-the-go adaptations. We suggest that such adaptations of implementation strategies consist of three necessary steps. The first component is the initial effect of the implementation approach on intended implementation, service delivery, or clinical outcomes. Second, these initial effects must in turn be used to modify, alter, intensify, or otherwise change the implementation approach. Third, the modified approach itself has effects. Conceiving of adaptation as all three steps implies that a full understanding of adaptation involves (a) a sense of initial effects, (b) conceptualizing and documenting content and rationale for changes in approach (e.g., alteration, intensification), and (c) the effects of the changed approach (including how the latter effects depend on initial effects). Conceptualizing these steps can help researchers ask questions about adaptation (e.g., thresholds for change, dosing, potentiation, sequencing) to advance our understanding of implementation strategies.

Strengthening implementation guidelines for HIV service delivery: Considerations for future evidence generation and synthesis.

Ingrid Eshun-Wilson and colleagues summarize gaps in primary HIV implementation research methods and reporting, and propose areas for future methodological development.

Trajectories of re-engagement: factors and mechanisms enabling patient return to HIV care in Zambia.

INTRODUCTION: While disengagement from HIV care threatens the health of persons living with HIV (PLWH) and incidence-reduction targets, re-engagement is a critical step towards positive outcomes. Studies that establish a deeper understanding of successful return to clinical care among previously disengaged PLWH and the factors supporting re-engagement are essential to facilitate long-term care continuity. METHODS: We conducted narrative, patient-centred, in-depth interviews between January and June 2019 with 20 PLWH in Lusaka, Zambia, who had disengaged and then re-engaged in HIV care, identified through electronic medical records (EMRs). We applied narrative analysis techniques, and deductive and inductive thematic analysis to identify engagement patterns and enablers of return. RESULTS: We inductively identified five trajectories of care engagement, suggesting patterns in patient characteristics, experienced barriers and return facilitators that may aid intervention targeting including: (1) intermittent engagement;(2) mostly engaged; (3) delayed linkage after testing; (4) needs time to initiate antiretroviral therapy (ART); and (5) re-engagement with ART initiation. Patient-identified periods of disengagement from care did not always align with care gaps indicated in the EMR. Key, interactive re-engagement facilitators experienced by participants, with varied importance across trajectories, included a desire for physical wellness and social support manifested through verbal encouragement, facility outreach or personal facility connections and family instrumental support. The mechanisms through which facilitators led to return were: (1) the promising of living out one's life priorities; (2) feeling valued; (3) fostering interpersonal accountability; (4) re-entry navigation support; (5) facilitated care and treatment access; and (6) management of significant barriers, such as depression. CONCLUSIONS: While preliminary, the identified trajectories may guide interventions to support re-engagement, such as offering flexible ART access to patients with intermittent engagement patterns instead of stable patients only. Further, for re-engagement interventions to achieve impact, they must activate mechanisms underlying re-engagement behaviours. For example, facility outreach that reminds a patient to return to care but does not affirm a patient's value or navigate re-entry is unlikely to be effective. The demonstrated importance of positive health facility connections reinforces a growing call for patient-centred care. Additionally, interventions should consider the important role communities play in fostering treatment motivation and overcoming practical barriers.

Multistate Modeling of Clinical Trajectories and Outcomes in the ICU: A Proof-of-Concept Evaluation of Acute Kidney Injury Among Critically Ill Patients With COVID-19.

Multistate models yield high-fidelity analyses of the dynamic state transition and temporal dimensions of a clinical condition's natural history, offering superiority over aggregate modeling techniques for addressing these types of problems. OBJECTIVES: To demonstrate the utility of these models in critical care, we examined acute kidney injury (AKI) development, progression, and outcomes in COVID-19 critical illness through multistate analyses. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study at an urban tertiary-care academic hospital in the United States. All patients greater than or equal to 18 years in an ICU with COVID-19 in 2020, excluding patients with preexisting end-stage renal disease. MAIN OUTCOMES AND MEASURES: Using electronic health record data, we determined AKI presence/stage in discrete 12-hour time windows and fit multistate models to determine longitudinal transitions and outcomes. RESULTS: Of 367 encounters, 241 (66%) experienced AKI (maximal stages: 88 stage-1, 49 stage-2, 104 stage-3 AKI [51 received renal replacement therapy (RRT), 53 did not]). Patients receiving RRT overwhelmingly received invasive mechanical ventilation (IMV) (n = 60, 95%) compared with the AKI-without-RRT (n = 98, 53%) and no-AKI groups (n = 39, 32%; p < 0.001), with similar mortality patterns (RRT: n = 36, 57%; AKI: n = 74, 40%; non-AKI: n = 23, 19%; p < 0.001). After 24 hours in the ICU, almost half the cohort had AKI (44.9%; 95% CI, 41.6-48.2%). At 7 days after stage-1 AKI, 74.0% (63.6-84.4) were AKI-free or discharged. By contrast, fewer patients experiencing stage-3 AKI were recovered (30.0% [24.1-35.8%]) or discharged (7.9% [5.2-10.7%]) after 7 days. Early AKI occurred with similar frequency in patients receiving and not receiving IMV: after 24 hours in the ICU, 20.9% of patients (18.3-23.6%) had AKI and IMV, while 23.4% (20.6-26.2%) had AKI without IMV. CONCLUSIONS AND RELEVANCE: In a multistate analysis of critically ill patients with COVID-19, AKI occurred early and heterogeneously in the course of critical illness. Multistate methods are useful and underused in ICU care delivery science as tools for understanding trajectories, prognoses, and resource needs.

Hospital trajectories and early predictors of clinical outcomes differ between SARS-CoV-2 and influenza pneumonia.

BACKGROUND: A comparison of pneumonias due to SARS-CoV-2 and influenza, in terms of clinical course and predictors of outcomes, might inform prognosis and resource management. We aimed to compare clinical course and outcome predictors in SARS-CoV-2 and influenza pneumonia using multi-state modelling and supervised machine learning on clinical data among hospitalised patients. METHODS: This multicenter retrospective cohort study of patients hospitalised with SARS-CoV-2 (March-December 2020) or influenza (Jan 2015-March 2020) pneumonia had the composite of hospital mortality and hospice discharge as the primary outcome. Multi-state models compared differences in oxygenation/ventilatory utilisation between pneumonias longitudinally throughout hospitalisation. Differences in predictors of outcome were modelled using supervised machine learning classifiers. FINDINGS: Among 2,529 hospitalisations with SARS-CoV-2 and 2,256 with influenza pneumonia, the primary outcome occurred in 21% and 9%, respectively. Multi-state models differentiated oxygen requirement progression between viruses, with SARS-CoV-2 manifesting rapidly-escalating early hypoxemia. Highly contributory classifier variables for the primary outcome differed substantially between viruses. INTERPRETATION: SARS-CoV-2 and influenza pneumonia differ in presentation, hospital course, and outcome predictors. These pathogen-specific differential responses in viral pneumonias suggest distinct management approaches should be investigated. FUNDING: This project was supported by NIH/NCATS UL1 TR002345, NIH/NCATS KL2 TR002346 (PGL), the Doris Duke Charitable Foundation grant 2015215 (PGL), NIH/NHLBI R35 HL140026 (CSC), and a Big Ideas Award from the BJC HealthCare and Washington University School of Medicine Healthcare Innovation Lab and NIH/NIGMS R35 GM142992 (PS).

Quantifying inequities in COVID-19 vaccine distribution over time by social vulnerability, race and ethnicity, and location: A population-level analysis in St. Louis and Kansas City, Missouri.

BACKGROUND: Equity in vaccination coverage is a cornerstone for a successful public health response to COVID-19. To deepen understanding of the extent to which vaccination coverage compares with initial strategies for equitable vaccination, we explore primary vaccine series and booster rollout over time and by race/ethnicity, social vulnerability, and geography. METHODS AND FINDINGS: We analyzed data from the Missouri Department of Health and Senior Services on all COVID-19 vaccinations administered across 7 counties in the St. Louis region and 4 counties in the Kansas City region. We compared rates of receiving the primary COVID-19 vaccine series and boosters relative to time, race/ethnicity, zip-code-level Social Vulnerability Index (SVI), vaccine location type, and COVID-19 disease burden. We adapted a well-established tool for measuring inequity-the Lorenz curve-to quantify inequities in COVID-19 vaccination relative to these key metrics. Between 15 December 2020 and 15 February 2022, 1,763,036 individuals completed the primary series and 872,324 received a booster. During early phases of the primary series rollout, Black and Hispanic individuals from high SVI zip codes were vaccinated at less than half the rate of White individuals from low SVI zip codes, but rates increased over time until they were higher than rates in White individuals after June 2021; Asian individuals maintained high levels of vaccination throughout. Increasing vaccination rates in Black and Hispanic communities corresponded with periods when more vaccinations were offered at small community-based sites such as pharmacies rather than larger health systems and mass vaccination sites. Using Lorenz curves, zip codes in the quartile with the lowest rates of primary series completion accounted for 19.3%, 18.1%, 10.8%, and 8.8% of vaccinations while representing 25% of the total population, cases, deaths, or population-level SVI, respectively. When tracking Gini coefficients, these disparities were greatest earlier during rollout, but improvements were slow and modest and vaccine disparities remained across all metrics even after 1 year. Patterns of disparities for boosters were similar but often of much greater magnitude during rollout in fall 2021. Study limitations include inherent limitations in the vaccine registry dataset such as missing and misclassified race/ethnicity and zip code variables and potential changes in zip code population sizes since census enumeration. CONCLUSIONS: Inequities in the initial COVID-19 vaccination and booster rollout in 2 large US metropolitan areas were apparent across racial/ethnic communities, across levels of social vulnerability, over time, and across types of vaccination administration sites. Disparities in receipt of the primary vaccine series attenuated over time during a period in which sites of vaccination administration diversified, but were recapitulated during booster rollout. These findings highlight how public health strategies from the outset must directly target these deeply embedded structural and systemic determinants of disparities and track equity metrics over time to avoid perpetuating inequities in healthcare access.

Temporal changes in paediatric and adolescent HIV outcomes across the care continuum in Zambia: an interrupted time-series analysis.

BACKGROUND: Paediatric and adolescent HIV treatment programmes in sub-Saharan Africa have rapidly expanded and evolved over the past decade. Real-world evidence of how the implementation of new policies over time has affected treatment outcomes is inadequate, but is crucial for guiding the implementation of the next phases of the HIV treatment response for children. We examined how treatment outcomes in Zambia's national paediatric and adolescent HIV treatment programmes have changed over time as new policies were implemented. METHODS: We used data from Zambia's routine electronic health record to analyse children and adolescents living with HIV who were antiretroviral therapy (ART) naive between the ages of 0 and 19 years who were newly enrolled in care between Jan 1, 2011, and March 31, 2019, at 102 health facilities in Lusaka and Western provinces supported by the Centre for Infectious Disease Research in Zambia. Sociodemographic factors, clinical data, facility-level data, and visit history were obtained from the national electronic health record and laboratory systems used in routine HIV care in Zambia. We aimed to characterise the changes in the distribution of the age and sex of new enrolees over time. We used an interrupted time-series design to examine the rates of ART initiation, retention in care, time to ART initiation, and first-line ART regimens among new enrolees across different age strata as they changed over time with the adoption of new ART guidelines in 2014 and 2017. FINDINGS: Between Jan 1, 2011, and March 31, 2019, 26 214 children and adolescents living with HIV who were ART naïve were newly enrolled at one of 102 ART facilities in two provinces in Zambia. Rates of new enrolees increased by 25-35% among children younger than 15 years over time, but by 92·3% between 2011 and 2017 among adolescents, with the largest absolute increase among adolescent girls. Rates of ART initiation increased steadily and in parallel across all age groups from before the implementation of the 2014 guidelines to after the implementation of the 2017 guidelines (<2 years, 42·4% for 2014 and 81·6% for 2017; 2 to <5 years, 39·3% for 2014 and 82·8% for 2017; 5 to <15 years, 49·2% for 2014 and 86·6% for 2017; 15 to 19 years, 52·4% for 2014 and 86·2% for 2017); median time to ART initiation went from 2-3 months to same-day initiation during this same time period. Rates of retention on ART 6 months after linkage saw much smaller improvements over time (<2 years, 35·4% for 2014 and 52·0% for 2017; 2 to <5 years, 40·2% for 2014 and 54·4% for 2017; 5 to <15 years, 46·7% for 2014 and 63·4% for 2017; 15 to 19 years, 40·1% for 2014 and 52·7% for 2017). INTERPRETATION: Improvements in ART initiation occurred largely in parallel across age groups over time, despite universal treatment being implemented at different timepoints for different ages. Although the rates of ART initiation reach high levels, retention on ART was low. This analysis provides a comprehensive examination of how paediatric and adolescent outcomes have evolved over the past decade in Zambia and identifies where more targeted efforts will be needed over the next decade. FUNDING: National Institutes of Health.

Data Velocity in HIV-Related Implementation Research: Estimating Time From Funding to Publication.

BACKGROUND: Given available effective biomedical and behavioral prevention and treatment interventions, HIV-related implementation research (IR) is expanding. The rapid generation and dissemination of IR to inform guidelines and practice has the potential to optimize the impact of the Ending the Epidemic Initiative and the HIV pandemic response more broadly. METHODS: We leveraged a prior mapping review of NIH-funded awards in HIV and IR from January 2013 to March 2018 and identified all publications linked to those grants in NIH RePORTER through January 1, 2021 (n = 1509). Deduplication and screening of nonoriginal research reduced the count to 1032 articles, of which 952 were eligible and included in this review. Publication volume and timing were summarized; Kaplan-Meier plots estimated time to publication. RESULTS: Among the 215 NIH-funded IR-related awards, 127 of 215 (59%) published original research directly related to the grant, averaging 2.0 articles (SD: 3.3) per award, largely in the early IR phases. Many articles (521 of 952, 55%) attributed to grants did not report grant-related data. Time from article submission to publication averaged 205 days (SD: 107). The median time-to-first publication from funding start was 4 years. Data dissemination velocity varied by award type, trending toward faster publication in recent years. Delays in data velocity included (1) time from funding to enrollment, (2) enrollment length, and (3) time from data collection completion to publication. CONCLUSION: Research publication was high overall, and time-to-publication is accelerating; however, over 40% of grants have yet to publish findings from grant-related data. Addressing bottlenecks in the production and dissemination of HIV-related IR would reinforce its programmatic and policy relevance in the HIV response.

Five Common Myths Limiting Engagement in HIV-Related Implementation Research.

ABSTRACT: HIV-related implementation research holds great promise in achieving the potential of efficacious prevention and treatment tools in reducing the incidence of HIV and improving HIV treatment outcomes among people living with HIV. From the perspectives of HIV-related implementation research training and academia and through consultations with funders and investigators new to implementation research, we identified 5 myths that act as barriers to engagement in implementation research among new investigators. Prevailing myths broadly include (1) one must rigidly apply all aspects of an implementation framework for it to be valid, (2) implementation research limits the type of designs available to researchers, (3) implementation strategies cannot be patient-level or client-level approaches, (4) only studies prioritizing implementation outcomes are "true" implementation research, and (5) if not explicitly labeled implementation research, it may have limited impact on implementation. We offer pragmatic approaches to negotiate these myths with the goal of encouraging dialog, ensuring high-quality research, and fostering a more inclusive and dynamic field of implementation research. Ultimately, the goal of dispelling these myths was to lower the perceived bar to engagement in HIV-related implementation research while still ensuring quality in the methods and measures used.

'I need time to start antiretroviral therapy': understanding reasons for delayed ART initiation among people diagnosed with HIV in Lusaka, Zambia'.

INTRODUCTION: Rapid antiretroviral therapy (ART) initiation can improve patient outcomes such as viral suppression and prevent new infections. However, not everyone who can start ART does so immediately. METHODS: We conducted a qualitative study to inform interventions supporting rapid initiation in the 'Test and Start' era. We purposively sampled 20 adult patients living with HIV and a previous gap in care from ten health facilities in Lusaka, Zambia for interviews. We inductively analysed transcripts using a thematic, narrative approach. In their narratives, seven participants discussed delaying ART initiation. RESULTS: Drawing on messages gleaned from facility-based counselling and community information, many cited greater fear of rapid sickness or death due to imperfect adherence or treatment side effects than negative health consequences due to delayed initiation. Participants described needing time to 'prepare' their minds for a lifetime treatment commitment. Concerns about inadvertent HIV status disclosure during drug collection discouraged immediate initiation, as did feeling healthy, and worries about the impact of ART initiation on relationship dynamics. CONCLUSION: Findings suggest that counselling messages should accurately communicate treatment risks, without perpetuating fear-based narratives about HIV. Identifying and managing patient-specific concerns and reasons for the 'need for time' may be important for supporting individuals to rapidly accept lifelong treatment.Key messagesFear-based adherence messaging in health facilities about the dangers of missing a treatment dose or changing the time when ART is taken contributes to Zambian patients' refusals of immediate ART initiationResponsive health systems that balance a stated need for time to accept one's diagnosis and prepare to embark on a lifelong treatment plan with interventions to identify and manage patient-specific treatment related fears and concerns may support more rapid ART initiationPerceived social stigma around HIV continues to be a significant challenge for treatment initiation.

Evaluation of HIV treatment outcomes with reduced frequency of clinical encounters and antiretroviral treatment refills: A systematic review and meta-analysis.

BACKGROUND: Global HIV treatment programs have sought to lengthen the interval between clinical encounters for people living with HIV (PLWH) who are established on antiretroviral treatment (ART) to reduce the burden of seeking care and to decongest health facilities. The overall effect of reduced visit frequency on HIV treatment outcomes is however unknown. We conducted a systematic review and meta-analysis to evaluate the effect of implementation strategies that reduce the frequency of clinical appointments and ART refills for PLWH established on ART. METHODS AND FINDINGS: We searched databases​ between 1 January 2010 and 9 November 2021 to identify randomized controlled trials (RCTs) and observational studies that compared reduced (6- to 12-monthly) clinical consultation or ART refill appointment frequency to 3- to 6-monthly appointments for patients established on ART. We assessed methodological quality and real-world relevance, and used Mantel-Haenszel methods to generate pooled risk ratios (RRs) with 95% confidence intervals for retention, viral suppression, and mortality. We evaluated heterogeneity quantitatively and qualitatively, and overall evidence certainty using GRADE. Searches yielded 3,955 records, resulting in 10 studies (6 RCTs, 3 observational studies, and 1 study contributing observational and RCT data) representing 15 intervention arms with 33,599 adults (≥16 years) in 8 sub-Saharan African countries. Reduced frequency clinical consultations occurred at health facilities, while reduced frequency ART refills were delivered through facility or community pharmacies and adherence groups. Studies were highly pragmatic, except for some study settings and resources used in RCTs. Among studies comparing reduced clinical consultation frequency (6- or 12-monthly) to 3-monthly consultations, there appeared to be no difference in retention (RR 1.01, 95% CI 0.97-1.04, p = 0.682, 8 studies, low certainty), and this finding was consistent across 6- and 12-monthly consultation intervals and delivery strategies. Viral suppression effect estimates were markedly influenced by under-ascertainment of viral load outcomes in intervention arms, resulting in inconclusive evidence. There was similarly insufficient evidence to draw conclusions on mortality (RR 1.12, 95% CI 0.75-1.66, p = 0.592, 6 studies, very low certainty). For ART refill frequency, there appeared to be little to no difference in retention (RR 1.01, 95% CI 0.98-1.06, p = 0.473, 4 RCTs, moderate certainty) or mortality (RR 1.45, 95% CI 0.63-3.35, p = 0.382, 4 RCTs, low certainty) between 6-monthly and 3-monthly visits. Similar to the analysis for clinical consultations, although viral suppression appeared to be better in 3-monthly arms, effect estimates were markedly influence by under-ascertainment of viral load outcomes in intervention arms, resulting in overall inclusive evidence. This systematic review was limited by the small number of studies available to compare 12- versus 6-monthly clinical consultations, insufficient data to compare implementation strategies, and lack of evidence for children, key populations, and low- and middle-income countries outside of sub-Saharan Africa. CONCLUSIONS: Based on this synthesis, extending clinical consultation intervals to 6 or 12 months and ART dispensing intervals to 6 months appears to result in similar retention to 3-month intervals, with less robust conclusions for viral suppression and mortality. Future research should ensure complete viral load outcome ascertainment, as well as explore mechanisms of effect, outcomes in other populations, and optimum delivery and monitoring strategies to ensure widespread applicability of reduced frequency visits across settings.