Electronic Adherence Monitoring Research Articles

Intake Patterns and Experiences of Patients Using Direct Oral Anticoagulants Measured by Electronic Monitoring in Community Pharmacies.

Several international organizations advocate for monitoring of adherence to direct oral anticoagulants (DOACs), given the prevalent issue of suboptimal adherence to DOACs. The aim was to investigate intake patterns in patients on DOAC therapy by electronic monitoring of medication adherence in community pharmacies (using a Medication Event Monitoring System® (MEMS®)-device), and to assess patients' experiences with this device. Patients using apixaban, rivaroxaban or edoxaban and visiting a community pharmacy, were included. Adherence was electronically monitored over a twelve-week period. Pharmacists conducted data readings from the electronic device at six and twelve weeks, and discussed these data with the patients. At the beginning and end of the study, patients completed a questionnaire about their expectations and experiences respectively. Eighty-nine patients were included and high taking adherence rates were observed (median adherence of 100% for once-daily dosed patients and 96.7% for twice-daily dosed patients), but more than half of the patients took at least one dose too late or skipped at least one dose, possibly resulting in temporarily reduced protection against thromboembolic events. Most patients who felt that their adherence had improved, believed this was due to the combination of the electronic device and the personal follow-up by the pharmacist. Although most patients stated that medication adherence is their own responsibility, they were grateful for the support they received from their community pharmacist. High adherence rates were observed, but there was still room for improvement regarding intake moments. Positive experiences with an electronic device for medication adherence monitoring were reported.

Study protocol for ADHERE (Applying Directly observed therapy to HydroxyurEa to Realize Effectiveness): Using small business partnerships to deliver a scalable and novel hydroxyurea adherence solution to youth with sickle cell disease.

Sickle cell disease (SCD) is an inherited blood disorder that affects approximately 100,000 Americans, primarily from underrepresented racial minority populations, and results in costly, multi-organ complications. Hydroxyurea, the primary disease-modifying therapy for SCD, is effective at reducing most complications; however, adherence to hydroxyurea remains suboptimal and is the primary barrier to clinical effectiveness. Video directly observed therapy (VDOT) has shown promise as an adherence-promoting intervention for hydroxyurea, yet previous VDOT trials were limited by high attrition from gaps in technology access, use of unvalidated adherence measures, and healthcare system limitations of delivering VDOT to patients. As such, we fostered a small business partnership to compare VDOT for hydroxyurea to attention control to address previous shortcomings, promote equitable trial participation, and maximize scalability. VDOT will be administered by Scene Health (formerly emocha Health) and adherence monitoring will be performed using a novel electronic adherence monitor developed to meet the unique needs of the target population. Adolescent and young adult patients as well as caregivers of younger patients (<11 years of age) will be recruited. In addition to visit incentives, all participants will be offered a smartphone with a data plan to ensure all participants have equal opportunity to complete study activities. The primary objectives of this pilot, multi-center, randomized controlled trial (RCT) are to assess retention and sustained engagement and to explore needs and preferences for longer-term adherence monitoring and interventions. This RCT is registered with the National Institutes of Health (NCT06264700). Findings will inform a future efficacy RCT applying VDOT to hydroxyurea to address adherence gaps and improve outcomes within this vulnerable population.

Performance of Medication Tasks: Relationship Among Patient-Reported Outcomes, Performance-Based Assessments, and Objective Assessments.

Occupational therapy practitioners use standardized assessments to guide their clinical decision-making, but it is unclear how well performance on standardized assessments translates to performance at home. To understand the concurrent and predictive validity of patient-reported outcomes and performance-based assessments for monitoring performance at home within the context of medication management and adherence. Exploratory study. Participants completed standardized assessments in a lab or at home, which were followed by home-based electronic monitoring of medication adherence. Sixty community-dwelling adults with hypertension or stroke who independently took antihypertensive medications. Participants completed the Hill-Bone Medication Adherence Scale, the Hill-Bone Medication Adherence Reasons Scale, the Performance Assessment of Self-Care Skills Medication Management subtask, and the Executive Function Performance Test-Enhanced Medication Management subtest. Then, they used an electronic pill cap to monitor medication adherence at home for 1 month. Patient-reported outcomes and performance-based assessments in the context of medication management and adherence demonstrated poor concurrent and predictive validity to medication adherence at home. There is a gap between what people think they will do, what they can do on a standardized assessment, and what they actually do at home. Future research is needed to strengthen concurrent and predictive validity to clinically meaningful outcomes. Plain-Language Summary: Occupational therapy practitioners should use caution when using standardized assessments to try to predict client performance at home. They should also continue to use a battery of assessments, clinical reasoning, and client preferences to guide their decision-making for monitoring performance at home within the context of medication management and adherence.

Ethical considerations in using sensors to remotely assess pediatric health behaviors.

Sensors, including accelerometer-based and electronic adherence monitoring devices, have transformed health data collection. Sensors allow for unobtrusive, real-time sampling of health behaviors that relate to psychological health, including sleep, physical activity, and medication-taking. These technical strengths have captured scholarly attention, with far less discussion about the level of human touch involved in implementing sensors. Researchers face several subjective decision points when collecting health data via sensors, with these decisions posing ethical concerns for users and the public at large. Using examples from pediatric sleep, physical activity, and medication adherence research, we pose critical ethical questions, practical dilemmas, and guidance for implementing health-based sensors. We focus on youth given that they are often deemed the ideal population for digital health approaches but have unique technology-related vulnerabilities and preferences. Ethical considerations are organized according to Belmont principles of respect for persons (e.g., when sensor-based data are valued above the subjective lived experiences of youth and their families), beneficence (e.g., with sensor data management and sharing), and justice (e.g., with sensor access and acceptability among minoritized pediatric populations). Recommendations include the need to increase transparency about the extent of subjective decision making with sensor data management. Without greater attention to the human factors involved in sensor research, ethical risks could outweigh the scientific promise of sensors, thereby negating their potential role in improving child health and care. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Adherence Monitoring Package (AMoPac) in patients suspected of non-response to antihypertensive treatment: perceived usefulness by general practitioners

BackgroundNon-adherence to antihypertensive agents is common, mainly because of the low perceived burden of high blood pressure. General practitioners (GPs) are unable to predict whether patients are adhering to a...

Digital Pharmacotherapy Support for Medication Adherence

Scientific relevance. Medication adherence is an important condition for effective and safe treatment. The adherence of patients to prescriptions is tracked by assessing their condition, counting the pills taken, and using other indirect methods. Digital technologies can help healthcare providers improve their patients’ medication adherence.Aim. The authors aimed to review literature describing the medication adherence impact on treatment effectiveness, as well as digital solutions accompanying pharmacotherapy.Discussion. Poor adherence to treatment is a significant risk factor for patients. The most common examples of poor adherence are omissions and delays in the timing of doses. Compared with classical daily dosing, individualised regimens significantly increase the risk of adherence errors. Significant consequences of non-adherence include exacerbation of the disease, insufficient effectiveness of treatment, adverse drug reactions, and drug resistance. Promising hardware and software approaches to supporting medication adherence include innovative technological solutions (pillboxes, bottles with electronic reminder systems, digital pills, and smart medication adherence monitoring systems), mobile apps, and chatbots.Conclusions. Digital solutions to support pharmacotherapy help improve patients’ adherence to their dosing regimens and individualise their treatment. Further research is needed to select the most promising areas and develop novel digital technologies.

Performance of Multiple Adherence Measures for pre-exposure Prophylaxis (PrEP) Among Young Women in Kenya.

Understanding PrEP adherence is key in the formulation of HIV prevention strategies; however, measurement of adherence can be challenging. We compared multiple adherence measures in a two-year study of young Kenyan women at high risk of HIV acquisition. Among 289 participants, concordance between electronic adherence monitoring (EAM) and tenofovir diphosphate (TFV-DP) in dried blood spots ranged from 57 to 72% depending on selected thresholds. Using area under the receiver operating curve, discrimination of quantifiable TFV-DP was high at 0.85 with EAM and low at 0.49-0.54 for multiple self-reported measures. Correlation between EAM and self-reported measures was low (r < 0.11) although correlation within self-reported measures was moderate (r > 0.69). These findings indicate that both TFV-DP and EAM are useful PrEP adherence tools. Adherence would benefit from better availability of less expensive versions of both measurement tools. Additionally, further research on TFV-DP thresholds is needed to inform interpretation and use in understanding PrEP adherence in this population.

Protocol for an evaluation of adherence monitoring and support interventions among people initiating antiretroviral therapy in Cape Town, South Africa—a multiphase optimization strategy (MOST) approach using a fractional factorial design

BackgroundSouth Africa bears a large HIV burden with 7.8 million people with HIV (PWH). However, due to suboptimal antiretroviral therapy (ART) adherence and retention in care, only 66% of PWH in South Africa are virally suppressed. Standard care only allows for suboptimal adherence detection when routine testing indicates unsuppressed virus. Several adherence interventions are known to improve HIV outcomes, yet few are implemented in routinely due to the resources required. Therefore, determining scalable evidence-based adherence support interventions for resource-limited settings (RLS) is a priority. The multiphase optimization strategy (MOST) framework allows for simultaneous evaluation of multiple intervention components and their interactions. We propose to use MOST to identify the intervention combination with the highest levels of efficacy and cost-effectiveness that is feasible and acceptable in primary care clinics in Cape Town.MethodsWe will employ a fractional factorial design to identify the most promising intervention components for inclusion in a multi-component intervention package to be tested in a future randomized controlled trial. We will recruit 512 participants initiating ART between March 2022 and February 2024 in three Cape Town clinics and evaluate acceptability, feasibility, and cost-effectiveness of intervention combinations. Participants will be randomized to one of 16 conditions with different combinations of three adherence monitoring components: rapid outreach following (1) unsuppressed virus, (2) missed pharmacy refill collection, and/or (3) missed doses as detected by an electronic adherence monitoring device; and two adherence support components: (1) weekly check-in texts and (2) enhanced peer support. We will assess viral suppression (<50 copies/mL) at 24 months as the primary outcome; acceptability, feasibility, fidelity, and other implementation outcomes; and cost-effectiveness. We will use logistic regression models to estimate intervention effects with an intention-to-treat approach, employ descriptive statistics to assess implementation outcomes, and determine an optimal intervention package.DiscussionTo our knowledge, ours will be the first study to use the MOST framework to determine the most effective combination of HIV adherence monitoring and support intervention components for implementation in clinics in a RLS. Our findings will provide direction for pragmatic, ongoing adherence support that will be key to ending the HIV epidemic.Trial registrationClinicalTrials.gov NCT05040841. Registered on 10 September 2021.

Comparing Predictive Ability of Two Objective Adherence Measures in a Community-Based Cohort on Antiretroviral Therapy in South Africa: Tenofovir Diphosphate Concentrations and Electronic Adherence Monitors.

Electronic adherence (EA) and tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) are objective measures of antiretroviral therapy (ART) adherence. We characterized the association between these measures in a prospective cohort of persons with HIV (PWH) on ART. Four primary health clinics in Cape Town, South Africa. We enrolled 250 virally suppressed PWH receiving tenofovir-based ART. We collected EA data, monthly viral load, and TFV-DP in DBS for 12 months. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) for future viral breakthrough (VB) (>400 copies/mL) for each adherence measure. Receiver operating characteristics (ROCs) provided the predictive power of these measures. Participants had a median (IQR) age of 34 (27-42); 78% were women. Twenty-one (8%) developed VB. Logistic regression showed that when percent EA and TFV-DP concentrations increased, the odds of VB decreased. This relationship was consistent at the time of VB (aOR of 0.41 [95% CI: 0.25 to 0.66] for TFV-DP and aOR of 0.64 [95% CI: 0.54 to 0.76] for EA) and for up to 2 months before VB. Both adherence measures predicted future VB at both 1 month and 2 months before viral load measurement. We established that 2 objective adherence measures, EA and TFV-DP in DBS, have a positive association with, and are both strongly predictive of, VB in a community-based South African cohort on ART. Future research is needed to determine the feasibility of implementing these adherence measures in resource-limited settings to facilitate adherence interventions.

Improving palbociclib adherence among women with metastatic breast cancer using a CONnected CUstomized Treatment Platform: A pilot study.

To pilot test a mobile health intervention using a CONnected CUstomized Treatment Platform that integrates a connected electronic adherence monitoring smartbox and an early warning system of non-adherence with bidirectional automated texting feature and provider alerts. In total, 29 adult women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer and a prescription for palbociclib were asked to complete a survey and participate in a CONnected CUstomized Treatment Platform intervention, including use of a smartbox for real-time adherence monitoring, which triggered text message reminders for any missed or extra dose, and referrals to (a) participant's oncology provider after three missed doses or an episode of over-adherence, or (b) a financial navigation program for any cost-related missed dose. Use of smartbox, number of referrals, palbociclib adherence, CONnected CUstomized Treatment Platform usability measured by System Usability Scale, and changes in symptom burden and quality of life were assessed. Mean age was 57.6 and 69% were white. The smartbox was used by 72.4% of participants, with palbociclib adherence rate of 95.8%±7.6%. One participant was referred to oncology provider due to missed doses and one was referred to financial navigation. At baseline, 33.3% reported at least one adherence barrier including inconvenience to get prescription filled, forgetfulness, cost, and side effects. There were no changes in self-reported adherence, symptom burden or quality of life over 3 months. CONnected CUstomized Treatment Platform usability score was 61.9 ± 14.2. The CONnected CUstomized Treatment Platform interventions is feasible, resulting in a high palbociclib adherence rate without any decline in overtime. Future efforts should focus on improving usability.

MyTPill: study protocol for a cross-over randomised controlled trial comparing novel strategies to monitor antiretroviral adherence among HIV+ prescription opioid users

IntroductionAdherence to HIV antiretroviral therapy (ART) remains the cornerstone of HIV treatment. For individuals with suboptimal adherence, electronic adherence monitoring (EAM) technologies have become an important component of multimodal adherence...

Eye Drop Adherence With an Eye Drop Bottle Cap Monitor.

An eye drop bottle cap monitor with audio and visual alarms measured eye drop adherence in 50 subjects with glaucoma. Baseline adherence rates were too high to test if the alarms could improve adherence. To determine if an eye drop bottle cap monitor can measure and improve adherence. The Devers Drop Device (D3, Universal Adherence LLC) was designed to measure eye drop adherence by detecting bottle cap removal and replacement, and it can provide text, visual and audio alerts when a medication is due. In Stage 1, we determined baseline adherence for 50 subjects using a nightly eye drop over a 25-day period. Subjects with less than 90% baseline adherence were eligible for Stage 2. In Stage 2, we randomized subjects to receive either no reminder or automated D3 alerts for their nightly eye drop over a subsequent 25-day period. We defined adherence as the proportion of drops administered within 3 hours of the subjects' scheduled dosing time. Subjects completed 3 questions regarding satisfaction with the device and willingness to pay. The D3 monitor remained attached to the eye drop bottle cap for the duration of the study and collected adherence data in all 50 patients. In Stage 1, the mean adherence rate was 90 ± 18% (range 32-100%). Forty (80%) subjects had an adherence rate greater than 90%. Adherence rates were too high in Stage 1 to adequately test the effects of reminders in Stage 2. Ninety-eight percent (49/50) and 96% (48/50) of subjects agreed "the device always stayed attached to the bottle cap" and "I was able to use the device to take the drops", respectively. Patients would pay $61±83 (range $0-400) for a similar device to improve adherence. The D3 can measure eye drop adherence. Research subjects reported high satisfaction and willingness to pay for an eye drop bottle cap monitor. Glaucoma patients have high adherence when they are being monitored, and future studies with research subjects screened for poor adherence may further determine the benefit of electronic monitoring of adherence with and without electronic reminders.

Improving the accuracy of adherence data collected using medication monitoring technology in clinical research

Ambiguous adherence data adversely effects the statistical analyses, study conclusions, and generalizability of research findings for clinical trials. Fortunately, technology-based measures of drug dosing provide more objective measures of medication adherence. While adherence data obtained through monitoring technology avoids the well documented shortcomings of self-reported adherence data, there are important limitations and nuances with use of these technologies that should be considered at study inception, conduct, and analysis. This article describes considerations for data collection and management with use of electronic adherence monitoring, specifically mobile-phone video applications or electronic pillbox devices. The overall aim of this communique is to provide research teams the ability to collect more accurate adherence data and ultimately improve the quality and outcome of their research.

Electronic monitoring of adherence in clinical care: Ethical and practical considerations.

Electronic monitoring of adherence in clinical care: Ethical and practical considerations.

Monitoring adherence to antiretroviral therapy among adolescents in Southern Uganda: comparing Wisepill to Self-report in predicting viral suppression in a cluster-randomized trial.

IntroductionOptimal antiretroviral therapy (ART) adherence is crucial for improved patient outcomes; however, ART adherence among adolescents living with HIV (ALHIV) is low. Also, the performance of various adherence measures among ALHIV is under contention. We monitored ART adherence and compared Self‐report (SR) and Wisepill electronic monitoring (EM) performance in measuring ART adherence and predicting HIV viral suppression among ALHIV.MethodsBetween January 2014 and December 2015, we recruited 702 ALHIV aged 10–16 years into our cluster‐randomized controlled trial (2012–2018) in 39 clinics in Uganda. The intervention included a long‐term savings child development account, four micro‐enterprise workshops and 12 mentorship sessions. Using the entire sample, we performed multilevel logistic regression to predict monthly ART adherence trends for the first year of follow‐up. Since it is possible that the intervention had different effects on SR and EM adherence, we used participants in the control arm only to compare adherence using SR and EM and to calculate their sensitivity and specificity in predicting viral suppression.ResultsThere was a significant decline in adherence for each month throughout the entire follow‐up period regardless of the group assigned. Good ART adherence was measured at 79.2% (75.2–82.6%) and 97.0% (95.4–98.1%) using EM and SR, respectively. Overall, 64.3% (60.6–67.9%) had suppressed viral loads. The specificities for EM and SR in predicting viral non‐suppression were 80.4% (73.6–85.7%) and 96.7% (93.3–98.4%), while the sensitivities were 22.9% (15.0–33.3%) and 1.8% (0.4–6.9%), respectively. The area under the curve was low for both EM and SR, at 53.6% (45.7–61.5%) and 56.2% (53.2–59.3%), respectively. There was high agreement (78%) between SR and EM in monitoring adherence.ConclusionsOur findings highlighted the need for strategies for sustained optimal adherence. SR and EM measure adherence with a considerable agreement; however, neither is an accurate predictor of virological outcome. There is still a need for an acceptable, feasible and affordable method that predicts viral suppression among ALHIV.

Key predictors of the need for a family-focused pediatric epilepsy adherence intervention.

ObjectiveNonadherence to antiseizure drugs is a significant problem in pediatric epilepsy and is linked to increased morbidity and mortality, clinically unnecessary medication changes, and increased health care costs. Family interventions can improve adherence. However, it is challenging to determine which families will struggle with nonadherence and require intervention. This study aims to identify specific parent, family, child, and medical factors that predict which families most need family‐based adherence interventions.MethodsFamilies enrolled in a randomized clinical trial of a family‐based adherence intervention completed measures assessing parent, family, child, and medical factors. Families also used an electronic adherence monitor. Adherence of ≥95% was considered high adherence (not requiring intervention), and <95% was considered suboptimal adherence (requiring intervention). We conducted a stepwise logistic regression analysis to assess demographic, medical, child, family, and parent predictors of membership to the suboptimal adherence group.ResultsOf the 200 families of children with new onset epilepsy who enrolled, 177 families completed the study. Of these families, 121 (68%) were in the high adherence group and 56 (32%) were in the suboptimal adherence group. Families with lower socioeconomic status (SES), children of color, lower general family functioning, and more parent distress were more likely to be in the suboptimal adherence group.SignificanceWe identified that parent and family factors, as well as sociodemographic characteristics, predicted membership in the suboptimal adherence group. It is critical to find creative and practical solutions for assessing and intervening upon key adherence predictors. These may include streamlined screening for parental distress and family functioning, as well as recognition that families of lower SES and communities of color may be at heightened risk for suboptimal adherence.

43-LB: Diabetes Distress, Depression, Perceived Stress, and Medication Adherence in Type 2 Diabetes (T2D)

Objective: Diabetes distress and depression are associated with treatment nonadherence among adults with T2D. Evidence for the independence of these effects has been mixed. Whether perceived stress, or the degree to which situations in life in general are appraised as stressful, can account for these effects has not been examined. We tested whether perceived stress was associated with objective T2D medication adherence and whether effects of diabetes distress and depression showed independence from perceived stress. Methods: Participants (N = 104, Age = 56.57 ± 9.32; A1C = 7.75 ± 1.55; 39% insulin use; 24% Latino, 24% White, 62.5% Black, 5.7% Other) completed validated self-reports of perceived stress, diabetes distress and depression and had oral medication adherence electronically monitored (EM) over 3 months. Multiple regression evaluated the association between perceived stress and EM medication adherence when modeled with covariates as well as with diabetes distress and depression. Results: Perceived stress was correlated with lower EM adherence (r = -.24, p = .013) ; however, when accounting for age, insulin use, and days of EM monitoring, the association was attenuated (β = -.14, p = .109) . Diabetes distress (β = -.29, p = .001) and depression (β = -.34, p &amp;lt; .001) were associated with lower adherence after covariate adjustment, when each were adjusted for perceived stress (diabetes distress: β = -.32, p = .005; depression: β = -.48, p &amp;lt; .001) , and when both were modeled together with perceived stress (diabetes distress: β = -.22, p = .044; depression: β = -.41, p = .002) . In this final model, perceived stress showed an unexpected positive association with adherence (β = .27, p = .035) . Conclusion: The associations of diabetes distress and depression with treatment nonadherence were not accounted for by perceived stress in this diverse sample of adults with T2D. Their independent associations with treatment nonadherence support both constructs as important targets for intervention. Disclosure F. Mustafiz: None. C. J. Hoogendoorn: None. J. S. Gonzalez: Consultant; Virta Health Corp.

Randomized Controlled Pilot Trial of a Low-Touch Remotely-Delivered Values Intervention to Promote Adherence to Adjuvant Endocrine Therapy Among Breast Cancer Survivors.

Oral anti-cancer treatments such as adjuvant endocrine therapies (AET) for breast cancer survivors are commonly used but adherence is a challenge. Few low-touch, scalable interventions exist to increase ET adherence. To evaluate the acceptability, feasibility, and initial efficacy of a low-touch, remotely-delivered values plus AET education intervention (REACH) to promote AET adherence. A mixed-methods trial randomized 88 breast cancer survivors 1:1 to REACH or Education alone. Wisepill real-time electronic adherence monitoring tracked monthly AET adherence during a 1-month baseline through 6-month follow-up (FU) (primary outcome). Patient-reported outcomes were evaluated through 3- and 6-month FU (secondary). Multiple indices of intervention feasibility and acceptability were evaluated. Qualitative exit interviews (n = 38) further assessed participants' perceptions of feasibility/acceptability and recommendations for intervention adaptation. The trial showed strong feasibility and acceptability, with an eligible-to-enrolled rate of 85%, 100% completion of the main intervention sessions, and "good" intervention satisfaction ratings on average. For Wisepill-assessed AET adherence, REACH outperformed Education for Month 1 of FU (p = .027) and not thereafter. Participants in REACH maintained high adherence until Month 4 of FU, whereas in Education, adherence declined significantly in Month 1. Conditions did not differ in self-reported adherence, positive affective attitudes, future intentions, or necessity beliefs. REACH trended toward less negative AET attitudes than Education at 3-month FU (p = .057) reflecting improvement in REACH (p = .004) but not Education (p = .809). Exploratory moderator analyses showed that average to highly positive baseline AET affective attitudes and oncologist-patient communication each predicted higher adherence following REACH than Education; low levels did not. Participants identified recommendations to strengthen the interventions. REACH, a low-touch values intervention, showed good feasibility and acceptability, and initial promise in improving objectively-assessed AET adherence among breast cancer survivors (relative to education alone). Future research should target improving REACH's tailoring and endurance.

Effect of electronic adherence monitoring on adherence and outcomes in chronic conditions: A systematic review and meta-analysis.

IntroductionElectronic adherence monitoring (EAM) is increasingly used to improve adherence. However, there is limited evidence on the effect of EAM in across chronic conditions and on patient acceptability. We aimed to assess the effect of EAM on adherence and clinical outcomes, across all ages and all chronic conditions, and examine acceptability in this systematic review and meta-analysis.MethodsA systematic search of Ovid MEDLINE, EMBASE, Social Work s, PsycINFO, International Pharmaceutical s and CINAHL databases was performed from database inception to December 31, 2020. Randomised controlled trials (RCTs) that evaluated the effect of EAM on medication adherence as part of an adherence intervention in chronic conditions were included. Study characteristics, differences in adherence and clinical outcomes between intervention and control were extracted from each study. Estimates were pooled using random-effects meta-analysis, and presented as mean differences, standardised mean differences (SMD) or risk ratios depending on the data. Differences by study-level characteristics were estimated using subgroup meta-analysis to identify intervention characteristics associated with improved adherence. Effects on adherence and clinical outcomes which could not be meta-analysed, and patient acceptability, were synthesised narratively. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed, and Risk of bias (RoB) assessed using the Cochrane Collaboration’s RoB tool for RCTs. The review is registered with PROSPERO CRD42017084231.FindingsOur search identified 365 studies, of which 47 studies involving 6194 patients were included. Data from 27 studies (n = 2584) were extracted for the adherence outcome. The intervention group (n = 1267) had significantly better adherence compared to control (n = 1317), (SMD = 0.93, CI:0.69 to 1.17, p<0.0001) with high heterogeneity across studies (I2 = 86%). There was a significant difference in effect according to intervention complexity (p = 0.01); EAM only improved adherence when used with a reminder and/or health provider support. Clinical outcomes were measured in 38/47 (81%) of studies; of these data from 14 studies were included in a meta-analysis of clinical outcomes for HIV, hypertension and asthma. In total, 13/47 (28%) studies assessed acceptability; patient perceptions were mixed.InterpretationPatients receiving an EAM intervention had significantly better adherence than those who did not, but improved adherence did not consistently translate into clinical benefits. Acceptability data were mixed. Further research measuring effects on clinical outcomes and patient acceptability are needed.

Effect of HIV Self-Testing on PrEP Adherence Among Gender-Diverse Sex Workers in Uganda: A Randomized Trial.

HIV self-testing (HIVST) and pre-exposure prophylaxis (PrEP) are complementary tools that could empower sex workers to control their HIV protection, but few studies have jointly evaluated PrEP and HIVST in any setting. The Empower Study was an open-label randomized trial in Uganda. Sex workers were offered F/tenofovir disoproxil fumarate and randomized 1:1 to monthly HIVST and quarterly in-clinic testing (intervention) or quarterly in-clinic HIV testing alone (standard of care) and followed up for 12 months. PrEP adherence was measured using electronic adherence monitoring and tenofovir diphosphate (TFV-DP) levels in dried blood spots. Adherence outcomes and sexual behaviors were compared by arm using generalized estimating equation models. We enrolled 110 sex workers: 84 cisgender women, 14 transgender women, 10 men who have sex with men, and 2 transgender men. The median age was 23 years. The 12-month retention was 75%. Nearly all (99.4%) used ≥1 HIVST kit. The proportion with TFV-DP levels ≥700 fmol/punch in the HIVST and standard of care arms at the 3-, 6-, 9-, and 12-month visits was 2.4%, 2.3%, 0%, and 0% and 7.9%, 0%, 0%, and 0%, respectively, with no differences by randomization arm (P > 0.2). Self-reported condomless sex acts with paying partners was similar by arm [adjusted incidence rate ratio 0.70; 95% confidence interval (CI): 0.42 to 1.17; P = 0.18]. One seroconversion occurred (HIV incidence, 0.9/100 person-years); TFV-DP was not detected at any visit. A gender-diverse sample of sex workers in Uganda used HIVST but not daily oral PrEP for HIV protection. Alternate approaches to promote PrEP use, including long-acting formulations, should be considered in this population.