Real-time Adherence Monitoring Research Articles

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.

A mixed-methods study of the technical feasibility and patient acceptability of a real-time adherence monitor in breast cancer survivors taking adjuvant endocrine therapy.

Oral anti-cancer medications are increasingly common and endocrine therapies represent the most common oral anti-cancer medications in breast cancer. Adjuvant endocrine therapies reduce the likelihood of recurrence and mortality in the approximately 80% of women diagnosed with hormone-receptor-positive breast cancer, thus rendering adherence essential. Real-time medication adherence monitors, such as the Wisepill electronic pillbox, transmit adherence data remotely, allowing for early intervention for non-adherence. However, their feasibility and acceptability have yet to be examined among breast cancer survivors taking endocrine therapies. This study presents quantitative patient-report and technical support data and qualitative patient acceptability data on Wisepill, a common real-time adherence monitor, among 88 breast cancer survivors prescribed adjuvant endocrine therapy. This mixed-methods study of a common real-time adherence monitor, among the first in breast cancer survivors taking adjuvant endocrine therapy, demonstrates its technical feasibility and patient acceptability. The use of wireless medication monitors that transmit real-time adherence data is uniquely promising for maximizing the benefits of adjuvant endocrine therapy by allowing for continuous tracking, ongoing communication with oncologic or research teams, and early intervention. This study demonstrates the feasibility and patient acceptability of one such real-time adherence monitor.

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.

"I'd feel like someone was watchin' me… watching for a good reason": perceptions of data privacy, access, and sharing in the context of real-time PrEP adherence monitoring among HIV-negative MSM with substance use.

Once-daily oral tenofovir/emtricitabine is highly effective as pre-exposure prophylaxis (PrEP) against HIV but is dependent on adherence, which may be challenging for men who have sex with men (MSM) and use substances. Digital pill systems (DPS) permit the direct, real-time measurement of adherence, though user perceptions of data privacy in this context are unknown. Thirty prospective DPS users - HIV-negative MSM with non-alcohol substance use - completed in-depth qualitative interviews exploring preferences around privacy, access, and sharing of DPS adherence data. Participants discussed some concerns about the impact of DPS use on personal privacy, and emphasized the need for robust data protections in the technology. Participants were interested in having on-demand access to their adherence data, and were most willing to share data with primary care providers and long-term relationship partners. Future investigations exploring bioethical frameworks around DPS use are warranted, and user preferences should inform best practices for protecting DPS data.

Project Khanya: results from a pilot randomized type 1 hybrid effectiveness-implementation trial of a peer-delivered behavioural intervention for ART adherence and substance use in HIV care in South Africa.

IntroductionSouth Africa (SA) has the highest number of people living with HIV (PLWH) globally, and a significant burden of alcohol and other drug use (AOD). Although integrating AOD treatment into HIV care may improve antiretroviral therapy (ART) adherence, this is not typically routine practice in SA or other low‐resource settings. Identifying interventions that are feasible and acceptable for implementation is critical to improve HIV and AOD outcomes.MethodsA pilot randomized hybrid type 1 effectiveness‐implementation trial (N = 61) was conducted to evaluate the feasibility and acceptability of Khanya, a task‐shared, peer‐delivered behavioral intervention to improve ART adherence and reduce AOD in HIV care in SA. Khanya was compared to enhanced treatment as usual (ETAU), a facilitated referral to on‐site AOD treatment. Implementation outcomes, defined by Proctor’s model, included feasibility, acceptability, appropriateness and fidelity. Primary pilot effectiveness outcomes were ART adherence at post‐treatment (three months) measured via real‐time electronic adherence monitoring, and AOD measured using biomarker and self‐report assessments over six months. Data collection was conducted from August 2018 to April 2020.Results and discussionNinety‐one percent of participants (n = 56) were retained at six months. The intervention was highly feasible, acceptable, appropriate and delivered with fidelity (>90% of components delivered as intended by the peer). There was a significant treatment‐by‐time interaction for ART adherence (estimate = −0.287 [95% CI = −0.507, −0.066]), revealing a 6.4 percentage point increase in ART adherence in Khanya, and a 22.3 percentage point decline in ETAU. Both groups evidenced significant reductions in alcohol use measured using phosphatidylethanol (PEth) (F(2,101) = 4.16, p = 0.01), significantly decreased likelihood of self‐reported moderate or severe AOD (F(2,104) = 7.02, p = 0.001), and significant declines in alcohol use quantity on the timeline follow‐back (F(2,102) = 21.53, p < 0.001). Among individuals using drugs and alcohol, there was a greater reduction in alcohol use quantity in Khanya compared to ETAU over six months (F(2,31) = 3.28, p = 0.05).ConclusionsResults of this pilot trial provide initial evidence of the feasibility and acceptability of the Khanya intervention for improving adherence in an underserved group at high risk for ongoing ART non‐adherence and HIV transmission. Implementation results suggest that peers may be a potential strategy to extend task‐sharing models for behavioral health in resource‐limited, global settings.

Implementation of a Real-Time Medication Intake Monitoring Technology Intervention in Community Pharmacy Settings: A Mixed-Method Pilot Study.

Innovative dispensing products offering real-time medication intake monitoring are being developed to address medication non-adherence. However, implementation of these interventions within the workflow of a community pharmacy is unknown. The purpose of this study was to explore factors affecting implementation of a real-time adherence-monitoring, multidose-dispensing system in community pharmacies. A mixed-method study was conducted with pharmacy staff, who packaged and dispensed medications in smart multidose packages and monitored real-time medication intake via web-portal. Pharmacy staff participated in semi-structured interviews. The Technology Acceptance Model, Theory of Planned Behaviour and Capability, Opportunity, Motivation, Behaviour Model informed the interview guide. Interview transcripts were analyzed thematically and findings were mapped back to the frameworks. The usability was assessed by the System Usability Scale (SUS). Three pharmacists and one pharmacy assistant with a mean of 19 years of practice were interviewed. Three themes and 12 subthemes were generated. Themes included: pharmacy workflow factors, integration factors, and pharmacist-perceived patient factors. The mean SUS was found to be 80.63. Products with real-time adherence monitoring capabilities are valued by pharmacists. A careful assessment of infrastructure—including pharmacy workload, manpower and financial resources—is imperative for successful implementation of such interventions in a community pharmacy setting.

Brief Report: Financial Incentives and Real-Time Adherence Monitoring to Promote Daily Adherence to HIV Treatment and Viral Suppression Among People Living With HIV: A Pilot Study.

Interventions to promote medication adherence and viral suppression are needed among HIV-positive individuals. We aimed to determine the feasibility, acceptability, and preliminary impact of daily financial incentives linked to real-time adherence monitoring among treatment-experienced individuals. At an HIV clinic in Philadelphia, we conducted a pilot randomized trial among treatment-experienced HIV-positive adults with unsuppressed viral loads (>400 copies/mL). Participants randomized to the intervention group were eligible for daily lottery-based financial rewards dependent on antiretroviral therapy (ART) adherence, measured by a wireless-enabled electronic pill bottle. Participants also received a financial incentive for achieving viral suppression at 3 months. The control group received the standard of care. We measured acceptance and feasibility through follow-up survey at 3 months, viral suppression at 3 months, and adherence. Among 29 participants, 28 (93%) completed 3-month follow-up, and 24 (83%) completed a 3-month laboratory visit. Electronic pill bottles were highly acceptable to participants, with most strongly agreeing that they worked well, were reliable, and easy to use. Among those who received the intervention, 77% were very satisfied with their experience. Among those who completed the 3-month laboratory visit, viral suppression was achieved by 40% in the intervention group and 29% in the control group. ART adherence ≥80% was achieved by 36% and 25% in the intervention and control groups, respectively. Daily financial incentives coupled with real-time adherence monitoring are a promising strategy to support ART adherence among HIV-positive individuals who are not virally suppressed. This novel approach warrants testing in a larger trial.

Effect of SMS reminders on PrEP adherence in young Kenyan women (MPYA study): a randomised controlled trial

Pre-exposure prophylaxis (PrEP) is highly effective for preventing HIV acquisition. However, adherence among young women (aged 18-24 years) has been challenging. SMS reminders have been shown to improve adherence to antiretroviral therapy in some contexts, including in combination with real-time adherence monitoring. We aimed to determine the effect of SMS reminders on PrEP adherence among young women in Kenya over a 2-year period. The monitoring PrEP among young adult women (MPYA) study was an open label randomised controlled trial involving young adult women at high risk of HIV in Thika and Kisumu, Kenya. Participants were recruited from colleges, vocational institutions, informal settlements, and community-based organisations supporting young women. Women had to be aged 18-24 years and at high risk of HIV acquisition (defined as a VOICE risk score of 5 or higher, or being in a serodiscordant relationship). Study staff randomly assigned participants (1:1) to receive either SMS reminders (SMS reminder group) or no reminders (no SMS reminder group). Study group assignment was known to trial staff but masked to investigators. Reminders were initially sent daily and participants could switch to as-needed reminders (ie, sent only if they missed opening the monitor as expected) after 1 month. Study visits occurred at 1 month, 3 months, and then quarterly (ie, every 3 months). The primary outcome was PrEP adherence over 24 months measured with a real-time electronic monitor and assessed by negative binomial models adjusted for the study site and quarter among participants who collected PrEP. This trial is registered with ClinicalTrials.gov, NCT02915367. Of 642 women initially approached, 348 eligible women were enrolled between Dec 21, 2016, and Feb 5, 2018. Participants were randomly assigned to either the SMS reminder group (n=173) or the no SMS reminder group (n=175). The median age was 21 years (IQR 19-22) and 228 (66%) of the 348 participants reported condomless sex in the month before baseline. 24 (14%) of the 173 participants assigned to receive daily SMS reminders later opted for as-needed reminders. 69 291 (97%) of 71 791 SMS reminders were sent as planned. Among participants collecting PrEP (thus potentially suggesting a desire for HIV protection), electronically monitored adherence averaged 26·8% over 24 months and was similar by study group (27·0% with SMS, 26·6% without SMS, adjusted incidence rate ratio 1·16 [95% CI 0·93-1·45], p=0·19). There were no serious adverse events related to trial participation; five social harms occurred in each study group, primarily related to PrEP use. SMS reminders were ineffective in promoting PrEP adherence among young Kenyan women. Given the overall low adherence in the trial, additional interventions are needed to support PrEP use in this population. US National Institute of Mental Health.

Perspectives on the utility and interest in a point-of-care urine tenofovir test for adherence to HIV pre-exposure prophylaxis and antiretroviral therapy: an exploratory qualitative assessment among U.S. clients and providers

BackgroundReal-time, objective measures of adherence to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are needed to better assess adherence levels and to expedite clinical response for those with suboptimal adherence. Point-of-care tenofovir (POC-TFV) testing has been proposed as a solution to facilitate real-time antiretroviral adherence monitoring, but little is known about how health care providers, people living with HIV (PLWH) receiving ART, and people receiving PrEP will perceive POC-TFV testing.MethodsWe conducted an exploratory qualitative study to assess perspectives on the utility and interest in POC-TFV testing from potential end users. We conducted three focus group discussions (FGDs) among 17 PLWH receiving ART and four individuals receiving PrEP, as well as eight in-depth interviews (IDIs) with health care providers in the Seattle area and presented participants with a hypothetical urine-based POC-TFV test. FGDs and IDIs were audio recorded, transcribed, coded, and analyzed to describe emerging themes.ResultsOverall, study participants demonstrated divergent opinions about the POC-TFV test. Among study participants, PLWH were most ambivalent about POC-TFV testing, first demonstrating reluctance to TFV-level monitoring and shifting positions during the FGDs. However, all PLWH participants were receptive to POC-TFV testing if requested by their provider. PrEP participants were generally supportive of POC-TFV testing for routine adherence monitoring and emphasized potential value in self-administered testing. Providers’ perceptions were equally divided – half suggested POC-TFV testing would be valuable, particularly for people receiving PrEP, while half indicated the test would have little benefit for most individuals receiving ART or PrEP in the U.S. All providers agreed that POC-TFV test results could be beneficial for assessing discrepancies in viral load results and self-reported adherence among PLWH. The study also revealed that a low-cost, non-urine-based POC-TFV test with a long-term limit of detection would be preferred over the hypothetical urine-based test.ConclusionsOur findings indicate POC-TFV testing may be beneficial for routine, clinic-based adherence monitoring, particularly for individuals receiving PrEP or for PLWH with persistent viremia or following recent ART initiation. These findings should also be used to formulate a target product profile for a POC-TFV test and to guide further developments in tools for objective antiretroviral adherence monitoring.

Testing a Real-Time Tenofovir Urine Adherence Assay for Monitoring and Providing Feedback to Preexposure Prophylaxis in Kenya (PUMA): Protocol for a Pilot Randomized Controlled Trial.

BackgroundThe worldwide expansion of preexposure prophylaxis (PrEP) with oral tenofovir-disoproxil-fumarate/emtricitabine will be critical to ending the HIV epidemic. However, maintaining daily adherence to PrEP can be difficult, and the accuracy of self-reported adherence is often limited by social desirability bias. Pharmacologic adherence monitoring (measuring drug levels in a biomatrix) has been critical to interpreting PrEP trials, but testing usually requires expensive equipment and skilled personnel. We have recently developed a point-of-care (POC) immunoassay to measure tenofovir in urine, allowing real-time adherence monitoring for the first time.ObjectiveThe goal of this study is to examine a point-of-care adherence metric in PrEP to support and increase adherence via a randomized controlled trial.MethodsThe paper describes the protocol for a pilot randomized controlled trial to test the acceptability, feasibility, and impact on long-term adherence of implementing a POC urine test to provide real-time adherence feedback among women on PrEP. Eligible women (n=100) will be HIV-negative, ≥18 years old, and recruited from a clinic in Kenya that provides PrEP. Participants will be randomized 1:1 to the intervention of providing real-time feedback via the assay versus standard of care adherence counseling. Acceptability by participants will be assessed by a quantitative survey, as well as by qualitative data collected via in-depth interviews (n=20) and focus group discussions (n=4 groups, 5-10 women each). Feasibility will be assessed by the proportion of women retained in the study, the mean number of missed visits, the proportion of planned urine assessments completed, and messages delivered, while in-depth interviews with providers (n=8) will explore the ease of administering the urine test. Tenofovir levels in hair will serve as long-term adherence metrics. A linear mixed-effects model will estimate the effect of the intervention versus standard of care on logarithmically transformed levels of tenofovir in hair.ResultsThis study has been funded by the National Institute of Health, approved by the Kenya Medical Research Institute Institutional Review Board, and will commence in June 2020.ConclusionsA novel urine assay to measure and deliver information on adherence to PrEP in real-time will be tested for the first time in this trial planned among women on PrEP in Kenya. Study findings will inform a larger-scale trial assessing the impact of real-time adherence monitoring/feedback on HIV prevention. Improving adherence to PrEP will have long-term implications for efforts to end the HIV epidemic worldwide.Trial RegistrationClinicalTrials.gov NCT03935464; https://clinicaltrials.gov/ct2/show/NCT03935464International Registered Report Identifier (IRRID)PRR1-10.2196/15029

Experience with antiretroviral electronic adherence monitoring among young African American men who have sex with men living with HIV: findings to inform a triaged real-time alert intervention

ABSTRACT We performed a pilot study among young African-American men who have sex with men (AAMSM) of real-time electronic adherence monitoring (EAM) in Chicago to explore acceptability and feasibility of EAM and to inform intervention development. We recruited 40 young AAMSM living with HIV on ART to participate in up to 3 months of monitoring with the Wisepill device. Participants were interviewed at baseline, in response to the first true adjudicated 1-dose, 3-day, and 7-day misses, and at the end of monitoring. Reasons for missing doses and the acceptability and feasibility of electronic monitoring were assessed using mixed methods. The median participant observation time was 90 days (N = 40). For 21 participants with 90 days of follow-up, <90% and <80% adherence occurred in 82% and 79%, respectively in at least one of their monitored months (n = 63 monitored months). The participants generally found the proposed intervention acceptable and useful. Although seven participants said the device attracted attention, none said it led to disclosure of their HIV status. This study found real-time EAM to be generally acceptable and feasible among YAAMSM living with HIV in Chicago. Future work will develop a triaged real-time EAM intervention including text alerts following detection of nonadherence.

Mobile Health Technologies May Be Acceptable Tools for Providing Social Support to Tuberculosis Patients in Rural Uganda: A Parallel Mixed-Method Study.

Background Social support has been shown to mitigate social barriers to medication adherence and improve tuberculosis (TB) treatment success rates. The use of mobile technology to activate social support systems among TB patients, however, has not been well explored. Moreover, studies that tie supportive SMS (Short Message Service) texts to electronic monitoring of TB medication adherence are lacking. Objective To explore TB patients' current access to social support and perceptions of utilizing real-time adherence monitoring interventions to support medication adherence. Methods We purposively selected TB patients who owned phones, had been taking TB medications for ≥1 month, were receiving their treatment from Mbarara Regional Referral Hospital, and reported having ≥1 social supporter. We interviewed these patients and their social supporters about their access to and perceptions of social support. We used STATA 13 to describe participants' sociodemographic and social support characteristics. Qualitative data were analyzed using content analysis to derive categories describing accessibility and perceptions. Results TB patients report requesting and receiving a variety of different forms of social support, including instrumental (e.g., money for transport and other needs and medication reminders), emotional (e.g., adherence counselling), and informational (e.g., medication side effects) support through mobile phones. Participants felt that SMS notifications may motivate medication adherence by creating a personal sense of obligation to take medications regularly. Participants anticipated that limited financial resources and relationship dynamics could constrain the provision of social support especially when patients and social supporters are not oriented about their expectations. Conclusion Mobile telephones could provide alternative approaches to providing social support for TB medication adherence especially where patients do not stay close to their social supporters. Further efforts should focus on optimized designs of mobile phone-based applications for providing social support to TB patients and training of TB patients and social supporters to match their expectations.

Using Real-Time Adherence Feedback to Enhance Communication About Adherence to Antiretroviral Therapy: Patient and Clinician Perspectives.

New technologies for real-time adherence monitoring hold the potential to enhance antiretroviral therapy adherence interventions by providing objective information about daily medication-taking behavior. To realize this potential, we need to understand how to integrate real-time adherence feedback into existing best practices to promote antiretroviral therapy adherence at the point of care. Using in-depth interviews with 30 HIV-infected patients and 29 HIV care clinicians, our primary aims were to understand patients' and clinicians' perceptions of anticipated benefits and preferred uses of objective feedback to enhance conversations about adherence and to identify concerns about the impact of objective monitoring on patient-clinician relationships and communication. Both patients and clinicians suggested that identifying patterns of nonadherence with real-time feedback could (a) facilitate collaborative adherence problem-solving, (b) motivate patient adherence, and (c) reinforce the importance of optimal adherence. Some clinicians worried that delivery of real-time feedback could imply mistrust of patient-reported adherence and suggested careful framing of monitoring results. A few patients and clinicians were concerned that negative reactions to monitoring could discourage retention in care and reduce adherence motivation. These results indicate the potential of real-time feedback to enhance existing evidence-based adherence interventions targeting the key adherence precursors of adherence information, motivation, and behavioral skills. Guidance for the delivery of real-time adherence feedback should focus on both optimizing adherence and mitigating negative perceptions of adherence monitoring.

2514. Real-time Antiretroviral Electronic Adherence Monitoring In Young African American Men Who Have Sex With Men

BackgroundAntiretroviral therapy adherence remains a challenge, particularly for young African American men who have sex with men (YAAMSM). We enrolled 40 YAAMSM for 3 months of electronic adherence monitoring (EAM). These data may be useful in developing an antiretroviral EAM intervention that responds to missed doses with real-time text messages.MethodsYAAMSM (age 18–34 years) living with HIV and taking ART participated in a quantitative and qualitative study that included ART adherence monitoring with a Wisepill electronic monitoring device for up to 3 months. Interviews were performed during April 2017–April 2019 at baseline and follow-up. Monitoring data were reviewed to determine timing and patterns of missing their first true adjudicated miss for durations of 1 dose, 3 consecutive days, and 7 consecutive days. Follow-up qualitative interviews included exploring acceptability of monitoring.ResultsThe median age was 28 years and median participant observation time was 90 days (interquartile range 88–90 days) (n = 40 participants). Among those with at least 2 weeks follow-up and adjudication (n = 32), 100% missed at least 1 day. Most (82%) of these participants were <80% adherent in at least one of their monitored months. One dose and 3-day misses did not cluster (e.g., no disproportion on weekends). Most (88%) first missed doses occurred during the first 9 days monitored and most (69%) of the 13 who missed 3 consecutive days missed within the first monitored month. Four participants missed 7 consecutive days. Among 31 with a follow-up interview, 28 (90%) felt receiving a text because of device monitoring would affect their medication taking in the future. Illustrative quotes included, “It made me more responsible” and “…it makes you want to do it right.”ConclusionMost YAAMSM living with HIV in this study had adherence below the target threshold of >80%. These data support development of a text message responsive real-time electronic adherence monitoring intervention approach.Disclosures All authors: No reported disclosures.

Electronic Health Interventions to Improve Adherence to Antiretroviral Therapy in People Living With HIV: Systematic Review and Meta-Analysis.

BackgroundElectronic health (eHealth) is increasingly used for self-management and service delivery of HIV-related diseases. With the publication of studies increasingly focusing on antiretroviral therapy (ART) adherence, this makes it possible to quantitatively and systematically assess the effectiveness and feasibility of eHealth interventions.ObjectiveThe purpose of this review was to explore the effectiveness of eHealth interventions on improving ART adherence in people living with HIV. The effects of different intervention characteristics, participant characteristics, and study characteristics were also assessed.MethodsWe systematically searched MEDLINE (via PubMed), EMBASE, the Cochrane Central Register of Controlled Trials, and 3 conference abstract databases using search terms related to HIV, ART, adherence, and eHealth interventions. We independently screened the studies, extracted the data, and assessed the study quality and then compared the information in pairs. Articles published in English that used randomized controlled trials to assess eHealth interventions to improve ART adherence of people living with HIV were identified. We extracted the data including study characteristics, participant characteristics, intervention characteristics, and outcome measures. The Cochrane risk-of-bias tool was used to assess the risk of bias and study overall quality. Odds ratios, Cohen d, and their 95% CIs were estimated using random-effects models. We also performed multiple subgroup analyses and sensitivity analyses to define any sources of heterogeneity.ResultsAmong 3941 articles identified, a total of 19 studies (including 21 trials) met the inclusion criteria. We found 8 trials from high-income countries and 13 trials from low- and middle-income countries. Furthermore, at baseline, the health status of participants in 14 trials was healthy. Of the trials included, 7 of 21 used personality content, 12 of 21 used a 2-way communication strategy, and 7 of 21 used medical content. In the pooled analysis of 3937 participants (mean age: 35 years; 47.16%, 1857/3937 females), eHealth interventions significantly improved the ART adherence of people living with HIV (pooled Cohen d=0.25; 95% CI 0.05 to 0.46; P=.01). The interventions were also correlated with improved biochemical outcomes reported by 11 trials (pooled Cohen d=0.25; 95% CI 0.11 to 0.38; P<.001). The effect was sensitive to sample size (Q=5.56; P=.02) and study duration (Q=8.89; P=.003), but it could not be explained by other moderators. The primary meta-analysis result was stable in the 3 sensitivity analyses.ConclusionsSome of the eHealth interventions may be used as an effective method to increase the ART adherence of people living with HIV. Considering that most of the trials included a small sample size and were conducted for a short duration, these results should be interpreted with caution. Future studies need to determine the features of eHealth interventions to better improve ART adherence along with long-term effectiveness of interventions, effectiveness of real-time adherence monitoring, enhancement of study design, and influences on biochemical outcomes.

A triaged real-time alert intervention to improve antiretroviral therapy adherence among young African American men who have sex with men living with HIV: focus group findings

BackgroundAmong persons living with HIV, poorer antiretroviral therapy adherence has been reported in African Americans and disproportionate mortality reported in young African American men who have sex with men (AAMSM) compared to whites. We report the results of focus groups with young AAMSM living with HIV that explore their opinions about the acceptability and feasibility of a triaged real-time missed dose alert intervention to improve treatment adherence.The purpose of this study is to develop a theory-driven triaged real-time adherence monitoring intervention to promote HIV medication adherence in young AAMSM.MethodsWe performed five focus groups and two individual interviews among young HIV-positive AAMSM (n = 25) in Chicago guided by the Technology Acceptance Model and explored perceptions regarding the monitoring concept including device issues and concerns about inclusion of support persons whose involvement is triggered by sustained missed doses. The purpose was to inform the development of this intervention in this population.ResultsGenerally, the participants found the proposed intervention acceptable and useful. Privacy was a major concern for participants especially with attention to possible disclosure of their HIV status by receiving a medication-related text that someone else might view and could lead to unwanted attention. There was concern that the device could be confused with a taser. Approximately half of the men already had a close personal contact that helped them with medication taking. Some participants acknowledged that the notification might lead to friction.ConclusionsA triaged real-time alert intervention to improve treatment adherence is acceptable and feasible among young AAMSM living with HIV.

Feasibility and Acceptability of Real-Time Antiretroviral Adherence Monitoring among Depressed Women Living with HIV in the Deep South of the US.

This study presents feasibility and acceptability data on the use of a real-time wireless electronic adherence monitor (EAM), among African American women living with HIV with co-occurring depression, residing in remote areas of the Southeastern United States. EAM and self-report ART adherence was monitored over an average of 14.8weeks among 25 participants who were recruited at four HIV clinics in Alabama. Intra-class correlation showed a low degree of concordance between EAM and self-report (ICC = 0.33, 95% bootstrap CI 0.13, 0.59). 83% of data collected via EAM was transmitted in real-time. Due to technological failures, 11.4% were not transmitted in real-time, but were later recovered, and 5.7% were lost entirely. Acceptability was examined through surveys and qualitative interviews. Results suggest that EAM monitoring is acceptable and feasible in a rural US setting; however, technological difficulties, such as loss of connectivity may impede the device's usefulness for just-in-time adherence interventions.

Impact of alcohol consumption on tuberculosis treatment outcomes: a prospective longitudinal cohort study protocol

BackgroundAn estimated 10% of tuberculosis (TB) deaths are attributable to problematic alcohol use globally, however the causal pathways through which problem alcohol use has an impact on TB treatment outcome is not clear. This study aims to improve understanding of these mechanisms. Specifically, we aim to 1) assess whether poor TB treatment outcomes, measured as delayed time-to-culture conversion, are associated with problem alcohol use after controlling for non-adherence to TB pharmacotherapy; and 2) to determine whether pharmacokinetic (PK) changes in those with problem alcohol use are associated with delayed culture conversion, higher treatment failure/relapse rates or with increased toxicity.MethodsOur longitudinal, repeated measures, prospective cohort study aims to examine the associations between problem alcohol use and TB treatment outcomes and to evaluate the effect of alcohol on the PK and pharmacodynamics (PD) of TB drugs. We will recruit 438 microbiologically confirmed, pulmonary TB patients with evidence of rifampicin susceptibility in Worcester, South Africa with 200 HIV uninfected patients co-enrolled in the PK aim. Participants are followed for the six months of TB treatment and an additional 12 months thereafter, with sputum collected weekly for the first 12 weeks of treatment, alcohol consumption measures repeated monthly in concert with an alcohol biomarker (phosphatidylethanol) measurement at baseline, and in person directly observed therapy (DOT) using real-time mobile phone-based adherence monitoring. The primary outcome is based on time to culture conversion with the second objective to compare PK of first line TB therapy in those with and without problem alcohol use.DiscussionGlobally, an urgent need exists to identify modifiable drivers of poor TB treatment outcomes. There is a critical need for more effective TB treatment strategies for patients with a history of problem alcohol use. However, it is not known whether poor treatment outcomes in alcohol using patients are solely attributable to noncompliance. This study will attempt to answer this question and provide guidance for future TB intervention trials.Trial registrationClinicaltrials.gov Registration Number: NCT02840877. Registered on 19 July 2016.

Actionable Adherence Monitoring: Technological Methods to Monitor and Support Adherence to Antiretroviral Therapy.

Current digital technologies are being used for "actionable adherence monitoring"; that is, technologies that can be used to identify episodes of non-adherence to ART in a timely manner such that tailored interventions based on adherence data can be provided when and where they are needed most. Current digital communication technologies used to monitor ART adherence include electronic adherence monitors (EAMs), digital ingestion monitors, cellular phones, and electronic pharmacy refill tracking systems. Currently available real-time adherence monitoring approaches based on cellular technology allow for the delivery of interventions precisely when and where they are needed. Such technology can potentially enable significant efficiency of care delivery and impact on adherence and associated clinical outcomes. Standard digital advances, such as automated reminders in EAM and electronic pharmacy records, may also achieve improvements with relatively lower cost and easier implementation. Future research is needed to improve the functionality of these approaches, with attention paid to system-level issues through implementation science, as well as acceptability and ethical considerations at the individual level.

Acceptability and Feasibility of Real-Time Antiretroviral Therapy Adherence Interventions in Rural Uganda: Mixed-Method Pilot Randomized Controlled Trial.

BackgroundWireless electronic adherence monitors can detect antiretroviral therapy (ART) adherence lapses and trigger interventions in real time, thus potentially avoiding unnecessary HIV viremia. Evidence about the acceptability and feasibility of these monitors and associated interventions, however, is limited.ObjectiveThe aim of this study was to assess the acceptability and feasibility of real-time adherence monitoring linked to text messaging (short message service, SMS) reminders and notifications to support adherence among individuals living with HIV who are taking ART in rural southwestern Uganda.MethodsIndividuals living with HIV who were initiating ART were enrolled in a pilot randomized controlled trial and followed up for 9 months. Participants received a real-time adherence monitor and were randomized to one of the following study arms: (1) scheduled SMS, (2) SMS triggered by missed or delayed doses, or (3) no SMS. SMS notifications were also sent to 45 patient-identified social supporters for sustained adherence lapses in the scheduled SMS and triggered SMS arms. Study participants and social supporters participated in qualitative semistructured in-depth interviews on acceptability and feasibility of this technology. An inductive, content analytic approach, framed by the unified theory of acceptance and use of technology model, was used to analyze qualitative data. Quantitative feasibility data, including device functionality and SMS tracking data, were recorded based upon device metrics collected electronically and summarized descriptively.ResultsA total of 63 participants participated in the study. Participants reported that real-time monitoring intervention linked to SMS reminders and notifications are generally acceptable; the predominant feedback was perceived utility—the intervention was beneficial in motivating and reminding patients to take medication, as well as enabling provision of social support.The intervention was found to be technically feasible, as data were obtained from most participants as expected most of the time. Potential challenges included the impact of the technology on confidentiality, shared phone ownership, usability skills, and availability of electricity.ConclusionsReal-time adherence monitoring integrated with SMS reminders and social support notifications is a generally acceptable (based primarily on perceived utility) and feasible intervention in a resource-limited country. Future efforts should focus on optimized device design, user training to overcome the challenges we encountered, cost effectiveness studies, as well as studying the monitoring aspect of the device without accompanying interventions.Trial RegistrationClinicalTrials.gov NCT01957865; https://clinicaltrials.gov/ct2/show/NCT01957865 (Archived by WebCite at http://www.webcitation.org/6zFiDlXDa)