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.

The integration of tuberculosis and HIV testing on GeneXpert can substantially improve access and same-day diagnosis and benefit tuberculosis programmes: A diagnostic network optimization analysis in Zambia.

Diagnostic network optimization (DNO), a geospatial optimization technique, can improve access to diagnostics and reduce costs through informing policy-makers' decisions on diagnostic network changes. In Zambia, viral load (VL) testing and early infant diagnosis (EID) for HIV has been performed at centralized laboratories, whilst the TB-programme utilizes a decentralized network of GeneXpert platforms. Recently, the World Health Organization (WHO) has recommended point-of-care (POC) EID/VL to increase timely diagnosis. This analysis modelled the impact of integrating EID/VL testing for children and pregnant/breastfeeding-women (priority-HIV) with TB on GeneXpert in Zambia. Using OptiDx, we established the baseline diagnostic network using inputs for testing demand (October 2019-September 2020), referrals, testing sites, testing platforms, and costs for HIV/TB testing (transport, test, device) respectively in Zambia. Next, we integrated priority-HIV testing on GeneXpert platforms, historically only utilized by the TB-programme. 228,265 TB tests were conducted on GeneXpert devices and 167,458 (99%) of priority-HIV tests on centralized devices at baseline, of which 10% were tested onsite at the site of sample collection. With integration, the average distance travelled by priority-HIV tests decreased 10-fold (98km to 10km) and the proportion tested onsite increased (10% to 48%). 52% of EID tests are likely to be processed within the same-day from a baseline of zero. There were also benefits to the TB-programme: the average distance travelled/specimen decreased (11km to 7km), alongside potential savings in GeneXpert device-operating costs (30%) through cost-sharing with the HIV-programme. The total cost of the combined testing programmes reduced marginally by 1% through integration/optimization. DNO can be used to strategically leverage existing capacity to achieve the WHO's recommendation regarding POC VL/EID testing. Through DNO of the Zambian network, we have shown that TB/HIV testing integration can improve the performance of the diagnostic network and increase the proportion of specimens tested closer to the patient whilst not increasing costs.

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

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

Preferences for services in a patient's first six months on antiretroviral therapy for HIV in South Africa and Zambia (PREFER): research protocol for a prospective observational cohort study.

Background: For patients on HIV treatment in sub-Saharan Africa, the highest risk for loss from care remains the first six months after antiretroviral (ART) initiation, when patients are not yet eligible for differentiated service delivery (DSD) models that offer lower-burden, patient-centred care and thus improve treatment outcomes. To reduce early disengagement from care, the PREFER study will use a sequential mixed-methods approach to describe the characteristics, needs, concerns, and preferences of patients in South Africa and Zambia 0-6 months after ART initiation or re-initiation. Protocol: PREFER is an observational, prospective cohort study of adults on ART for ≤6 months at 12 public healthcare facilities in Zambia and 18 in South Africa. Its objective is to describe and understand the needs and preferences of initiating and re-initiating ART clients to inform the design of DSD models for the early HIV treatment period, improve early treatment outcomes, and distinguish the barriers encountered by naïve patients from those facing re-initiators. It has four components: 1) survey of clients 0-6 months after ART initiation (identify characteristics and preferences of clients starting ART); 2) follow up through routinely collected medical records for <24 months after enrollment (describe resource utilization and patterns and predictors of engagement in care); 3) focus group discussions and discrete choice experiment (explore reported barriers to and facilitators of retention); and 4) in South Africa only, collection of blood samples (assess the prevalence of ARV metabolites indicating prior ART use). Conclusions: PREFER aims to understand why the early treatment period is so challenging and how service delivery can be amended to address the obstacles that lead to early disengagement from care. It will generate information about client characteristics and preferences to help respond to patients' needs and design better strategies for service delivery and improve resource allocation going forward.

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).

Integrating isoniazid preventive therapy into the fast-track HIV treatment model in urban Zambia: A proof-of -concept pilot project.

Most people living with HIV (PLHIV) established on treatment in Zambia receive multi-month prescribing and dispensing (MMSD) antiretroviral therapy (ART) and are enrolled in less-intensive differentiated service delivery (DSD) models such as Fast Track (FT), where clients collect ART every 3-6 months and make clinical visits every 6 months. In 2019, Zambia introduced Isoniazid Preventive Therapy (IPT) with scheduled visits at 2 weeks and 1, 3, and 6 months. Asynchronous IPT and HIV appointment schedules were inconvenient and not client centered. In response, we piloted integrated MMSD/IPT in FT HIV treatment model. We implemented and evaluated a proof-of-concept project at one purposively selected high-volume facility in Lusaka, Zambia between July 2019 and May 2020. We sensitized stakeholders, adapted training materials, standard operating procedures, and screened adults in FT for TB as per national guidelines. Participants received structured TB/IPT education, 6-month supply of isoniazid and ART, aligned 6th month IPT/MMSD clinic appointment, and phone appointments at 2 weeks and months 1-5 following IPT initiation. We used descriptive statistics to characterize IPT completion rates, phone appointment keeping, side effect frequency and Fisher's exact test to determine variation by participant characteristics. Key lessons learned were synthesized from monthly meeting notes. 1,167 clients were screened with 818 (70.1%) enrolled, two thirds (66%) were female and median age 42 years. 738 (90.2%) completed 6-month IPT course and 66 (8.1%) reported IPT-related side effects. 539 clients (65.9%) attended all 7 telephone appointments. There were insignificant differences of outcomes by age or sex. Lessons learnt included promoting project ownership, client empowerment, securing supply chain, adapting existing processes, and cultivating collaborative structured learning. Integrating multi-month dispensing and telephone follow up of IPT into the FT HIV treatment model is a promising approach to scaling-up TB preventive treatment among PLHIV, although limited by barriers to consistent phone access.

A controlled study to assess the effects of a Fast Track (FT) service delivery model among stable HIV patients in Lusaka Zambia.

Fast Track models-in which patients coming to facility to pick up medications minimize waiting times through foregoing clinical review and collecting pre-packaged medications-present a potential strategy to reduce the burden of treatment. We examine effects of a Fast Track model (FT) in a real-world clinical HIV treatment program on retention to care comparing two clinics initiating FT care to five similar (in size and health care level), standard of care clinics in Zambia. Within each clinic, we selected a systematic sample of patients meeting FT eligibility to follow prospectively for retention using both electronic medical records as well as targeted chart review. We used a variety of methods including Kaplan Meier (KM) stratified by FT, to compare time to first late pick up, exploring late thresholds at >7, >14 and >28 days, Cox proportional hazards to describe associations between FT and late pick up, and linear mixed effects regression to assess the association of FT with medication possession ratio. A total of 905 participants were enrolled with a median age of 40 years (interquartile range [IQR]: 34-46 years), 67.1% were female, median CD4 count was 499 cells/mm3 (IQR: 354-691), and median time on ART was 5 years (IQR: 3-7). During the one-year follow-up period FT participants had a significantly reduced cumulative incidence of being >7 days late for ART pick-up (0.36, 95% confidence interval [CI]: 0.31-0.41) compared to control participants (0.66; 95% CI: 0.57-0.65). This trend held for >28 days late for ART pick-up appointments, at 23% (95% CI: 18%-28%) among intervention participants and 54% (95% CI: 47%-61%) among control participants. FT models significantly improved timely ART pick up among study participants. The apparent synergistic relationship between refill time and other elements of the FT suggest that FT may enhance the effects of extending visit spacing/multi-month scripting alone. ClinicalTrials.gov Identifier: NCT02776254 https://clinicaltrials.gov/ct2/show/NCT02776254.

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

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

Mitigating the effects of COVID-19 on HIV treatment and care in Lusaka, Zambia: a before-after cohort study using mixed effects regression.

INTRODUCTION: The Zambian Ministry of Health (MoH) issued COVID-19 mitigation guidance for HIV care immediately after the first COVID-19 case was confirmed in Zambia on 18 March 2020. The Centre for Infectious Disease Research in Zambia implemented MoH guidance by: 1) extending antiretroviral therapy (ART) refill duration to 6 multi-month dispensation (6MMD) and 2) task-shifting communication and mobilisation of those in HIV care to collect their next ART refill early. We assessed the impact of COVID-19 mitigation guidance on HIV care 3 months before and after guidance implementation. METHODS: We reviewed all ART pharmacy visit data in the national HIV medical record for PLHIV in care having ≥1 visit between 1 January-30 June 2020 at 59 HIV care facilities in Lusaka Province, Zambia. We undertook a before-after evaluation using mixed-effects Poisson regression to examine predictors and marginal probability of early clinic return (pharmacy visit >7 days before next appointment), proportion of late visit (>7 days late for next appointment) and probability of receiving a 6MMD ART refill. RESULTS: A total of 101 371 individuals (64% female, median age 39) with 130 486 pharmacy visits were included in the analysis. We observed a significant increase in the adjusted prevalence ratio (4.63; 95% CI 4.45 to 4.82) of early return before compared with after guidance implementation. Receipt of 6MMD increased from a weekly mean of 47.9% (95% CI 46.6% to 49.2%) before to 73.4% (95% CI 72.0% to 74.9%) after guidance implementation. The proportion of late visits (8-89 days late) was significantly higher before (18.8%, 95% CI17.2%to20.2%) compared with after (15.1%, 95% CI13.8%to16.4%) guidance implementation . CONCLUSIONS: Timely issuance and implementation of COVID-19 mitigation guidance involving task-shifted patient communication and mobilisation alongside 6MMD significantly increased early return to ART clinic, potentially reducing interruptions in HIV care during a global public health emergency.

Differentiated Care Preferences of Stable Patients on Antiretroviral Therapy in Zambia: A Discrete Choice Experiment.

BACKGROUND: Although differentiated service delivery (DSD) models for stable patients on antiretroviral therapy (ART) offer a range of health systems innovations, their comparative desirability to patients remains unknown. We conducted a discrete choice experiment to quantify service attributes most desired by patients to inform model prioritization. METHODS: Between July and December 2016, a sample of HIV-positive adults on ART at 12 clinics in Zambia were asked to choose between 2 hypothetical facilities that differed across 6 DSD attributes. We used mixed logit models to explore preferences, heterogeneity, and trade-offs. RESULTS: Of 486 respondents, 59% were female and 85% resided in urban locations. Patients strongly preferred infrequent clinic visits [3- vs. 1-month visits: ß (ie, relative utility) = 2.84; P < 0.001]. Milder preferences were observed for waiting time for ART pick-up (1 vs. 6 hours.; ß = -0.67; P < 0.001) or provider (1 vs. 3 hours.; ß = -0.41; P = 0.002); "buddy" ART collection (ß = 0.84; P < 0.001); and ART pick-up location (clinic vs. community: ß = 0.35; P = 0.028). Urban patients demonstrated a preference for collecting ART at a clinic (ß = 1.32, P < 0.001), and although most rural patients preferred community ART pick-up (ß = -0.74, P = 0.049), 40% of rural patients still preferred facility ART collection. CONCLUSIONS: Stable patients on ART primarily want to attend clinic infrequently, supporting a focus in Zambia on optimizing multimonth prescribing over other DSD features-particularly in urban areas. Substantial preference heterogeneity highlights the need for DSD models to be flexible, and accommodate both setting features and patient choice in their design.

Immediate and early engagement of same-day antiretroviral therapy initiation among newly diagnosed people living with HIV in urban Zambia: a retrospective cohort study

Introduction: as Zambia moves towards attaining human immunodeficiency virus (HIV) epidemic control, it is clear significant efforts are required to facilitate achievement of UNAIDS treatment targets by 2030. To accelerate progress towards global target of 95% of people living with HIV (PLHIV) knowing their status, country is promoting community-based HIV testing and same-day antiretroviral therapy (ART) initiation. However, there are uncertainties of how this strategy affects immediate and early engagement in program settings. To address this research gap, we analysed a programme data of PLHIV newly diagnosed and initiated on ART in community and health facility settings. Study objectives were to estimate the proportion of immediate engagement, to estimate early engagement among newly diagnosed PLHIV and, to examine factors independently associated with immediate and early engagement in care among newly diagnosed PLHIV offered same-day ART initiation. Methods: we included all newly diagnosed PLHIV aged 18 years or older and provided same-day ART initiation between October 2018 and January 2019 in Lusaka District. Immediate engagement was estimated as proportion of newly diagnosed PLHIV who visited the health facility at least once within 14 days after same-day ART initiation, whereas early engagement as proportion of newly diagnosed PLHIV active 6 months after same-day ART initiation. Pearson's chi-squared test was used to assess association of outcomes with key background characteristics. Results: of 12,777 newly diagnosed PLHIV who initiated same day ART 7,943 (62%) were tested and initiated in the community. Overall, 6,257 (49%) engaged within 14 days (median 15, IQR: 13-37). Older individuals (36-49 years) were more likely to be engaged at 14 days (aRR 1.29; 95%CI 1.06 - 1.18; p<0.001) and retained at 6 months (aRR1.27;95%CI 1.21-1.34P<0.001) whilst risk of attrition at 6 months was highest in younger ages (18-24 years) (aRR 0.79;95 %CI 0.76-0.82; p<0.001). Conclusion: to adequately address the HIV epidemic targeted engagement approaches are required particularly in the younger ages.