Randomized controlled trial of a personalized cellular phone reminder system to enhance adherence to antiretroviral therapy

Adherence to antiretroviral therapy (ART) represents one of the strongest predictors of progression to AIDS, yet it is difficult for most patients to sustain high levels of adherence. This study compares the efficacy of a personalized cell phone reminder system (ARemind) in enhancing adherence to ART versus a beeper. Twenty-three HIV-infected subjects on ART with self-reported adherence less than 85% were randomized to a cellular phone (CP) or beeper (BP). CP subjects received personalized text messages daily; in contrast, BP subjects received a reminder beep at the time of dosing. Interviews were scheduled at weeks 3 and 6. Adherence to ART was measured by self-report (SR, 7-day recall), pill count (PC, past 30 days at baseline, then past 3 weeks), Medication Event Monitoring System (MEMS; cumulatively at 3 and 6 weeks), and via a composite adherence score constructed by combining MEMS, pill count, and self report. A mixed effects model adjusting for baseline adherence was used to compare adherence rates between the intervention groups at 3 and 6 weeks. Nineteen subjects completed all visits, 10 men and 9 females. The mean age was 42.7 ± 6.5 years, 37% of subjects were Caucasian and 89% acquired HIV heterosexually. The average adherence to ART was 79% by SR and 65% by PC at baseline in both arms; over 6 weeks adherence increased and remained significantly higher in the ARemind group using multiple measures of adherence. A larger and longer prospective study is needed to confirm these findings and to better understand optimal reminder messages and user fatigue.     

Controller adherence following hospital discharge in high risk children: A pilot randomized trial of text message reminders

Objective: To assess the feasibility of a mobile health, inhaled corticosteroid (ICS) adherence reminder intervention and to characterize adherence trajectories immediately following severe asthma exacerbation in high-risk urban children with persistent asthma. Methods: Children aged 2–13 with persistent asthma were enrolled in this pilot randomized controlled trial during an asthma emergency department (ED) visit or hospitalization. Intervention arm participants received daily text message reminders for 30 days, and both arms received electronic sensors to measure ICS use. Primary outcomes were feasibility of sensor use and text message acceptability. Secondary outcomes included adherence to prescribed ICS regimen and 30-day adherence trajectories. Group-based trajectory modeling was used to examine adherence trajectories. Results: Forty-one participants (mean age 5.9) were randomized to intervention (n = 21) or control (n = 20). Overall, 85% were Black, 88% had public insurance, and 51% of the caregivers had a high school education or less. Thirty-two participant families (78%) transmitted medication adherence data; of caregivers who completed the acceptability survey, 25 (96%) chose to receive daily reminders beyond that study interval. Secondary outcome analyses demonstrated similar average daily adherence between groups (intervention = 36%; control = 32%, P = 0.73). Three adherence trajectories were identified with none ever exceeding 80% adherence. Conclusions: Within a high-risk pediatric cohort, electronic monitoring of ICS use and adherence reminders delivered via text message were feasible for most participants, but there was no signal of effect. Adherence trajectories following severe exacerbation were suboptimal, demonstrating an important opportunity for asthma care improvement.     

Improving clinic attendance and adherence to antiretroviral therapy through a treatment supporter intervention in Uganda: a randomized controlled trial

We assessed the effectiveness of the treatment supporter initiative as an intervention in improving clinic attendance for antiretroviral (ARV) drug refills and adherence to antiretroviral therapy (ART) in a cohort of HIV-infected adults. This two-arm randomized controlled trial was undertaken at an HIV clinic in a district hospital in Uganda. A total of 174 adult patients on ART were randomized 1:1 to a standard adherence intervention package plus a treatment supporter intervention (TS arm) or to a standard adherence intervention package (non-TS arm) alone. Clinic attendance for refills and adherence measurements using monthly clinic-based pill counts were monitored for both arms for 28 weeks. Baseline characteristics were similar for both arms. There was a non-significant difference in mean adherence between the TS and non-TS groups at end of follow-up [99.1% (95% CI: 98.3–99.9% vs. 96.3% (95% CI: 94.2–98.3%), P > 0.05]. TS participants had more than four times the odds of achieving optimal adherence (≥95%) [Odds ratio (OR) = 4.51, 95% CI: 1.22–16.62, exact P = 0.027]. TS participants were also more likely to be on time for their clinic appointments: 91.6 vs. 90.1% for TS and non-TS, respectively (OR = 1.19, 95% CI: 0.74–1.91, P > 0.05). Use of patient-selected treatment supporters may be an effective intervention to improve ARV treatment outcomes in resource-constrained settings.     

Supporting patient adherence to antiretrovirals using mobile phone reminders: patient responses from South India

There has been exponential growth in the use of mobile phones in India over the last few years, and their potential benefits as a healthcare tool has raised tremendous interest. We used mobile phone reminders to help support adherence to antiretroviral therapy (ART) among HIV patients at an infectious disease clinic in a tertiary hospital in Bangalore. Between March and June 2010, 139 adult HIV patients taking regular ART for at least a month received weekly reminders to support adherence. These reminders consisted of a weekly interactive call and a non-interactive neutral pictorial short message service (SMS). After four weeks of the intervention, participants were interviewed to study perceptions on preference, usefulness, potential stigma and privacy concerns associated with this intervention. Majority of the participants were urban (89%), and had at least a secondary education (85%). A total of 744 calls were made, 545 (76%) of which were received by the participants. In addition, all participants received the weekly pictorial SMS reminder. A month later, 90% of participants reported the intervention as being helpful as medication reminders, and did not feel their privacy was intruded. Participants (87%) reported that they preferred the call as reminders, just 11% favoured SMS reminders alone. Only 59% of participants viewed all the SMSs that were delivered, while 15% never viewed any at all. Participants also denied any discomfort or stigma despite 20% and 13%, respectively, reporting that another person had inadvertently received their reminder call or SMS. Mobile phone interventions are an acceptable way of supporting adherence in this setting. Voice calls rather than SMSs alone seem to be preferred as reminders. Further research to study the influence of this intervention on adherence and health maintenance is warranted.     

Using Electronic Drug Monitor Feedback to Improve Adherence to Antiretroviral Therapy Among HIV-Positive Patients in China

Effective antiretroviral therapy (ART) requires excellent adherence. Little is known about how to improve ART adherence in many HIV/AIDS-affected countries, including China. We therefore assessed an adherence intervention among HIV-positive patients in southwestern China. Eighty subjects were enrolled and monitored for 6 months. Sixty-eight remaining subjects were randomized to intervention/control arms. In months 7–12, intervention subjects were counseled using EDM feedback; controls continued with standard of care. Among randomized subjects, mean adherence and CD4 count were 86.8 vs. 83.8% and 297 vs. 357 cells/μl in intervention vs. control subjects, respectively. At month 12, among 64 subjects who completed the trial, mean adherence had risen significantly among intervention subjects to 96.5% but remained unchanged in controls. Mean CD4 count rose by 90 cells/μl and declined by 9 cells/μl among intervention and control subjects, respectively. EDM feedback as a counseling tool appears promising for management of HIV and other chronic diseases.     

Feasibility of Interactive Text message Response (ITR) as a Novel, Real-Time Measure of Adherence to Antiretroviral Therapy for HIV+ Youth

Youth living with HIV/AIDS (YLH) face unique challenges to optimal adherence to antiretroviral therapy (ART). Accurate, real-time methods to assess adherence are needed to facilitate early intervention and promote viral suppression. The purpose of this study was to assess the feasibility and validity of interactive text message response (ITR) as a measure of adherence to ART among YLH. This study was part of a larger pilot text message reminder intervention conducted at a US community-based, LGBT-focused health center providing clinical services to YLH. Eligibility criteria for this pilot study included HIV-positive serostatus, aged 14–29, use of personal cell phone, English-speaking, and on ART with demonstrated adherence difficulties. During the 24-week study period, participants received personalized daily short message system reminders with a follow-up message 1 hour later asking whether they took medication and directing a response via return text message. To determine whether or not ITR would be a feasible, valid measure of adherence, we calculated the proportion of positive responses indicating medication had been taken divided by the total number of messages requesting a response and compared this response rate to a self-reported adherence measure, the visual analogue scale (VAS). Participants (n = 25) were on average 23 years old, largely male (92 %), Black (60 %) and behaviorally infected (84 %). Over the course of the intervention, study participants responded to prompts via text to indicate whether or not they had taken their medication approximately 61 % of the time. The overall mean ITR adherence rate (i.e., positive responses) was 57.4 % (SD = 28.5 %). ITR and VAS measures were moderately, positively correlated (r = 0.52, p < 0.05) during the first 6 weeks of the study period. ITR adherence rates were significantly higher on weekdays versus weekends (p < 0.05). This pilot study showed both moderate responsiveness of individuals to daily ITR and a moderate correlation of ITR adherence rates with a reliable measure during the first 6 weeks of the study, suggesting that this method, with additional effort and improvements, may be a helpful tool to identify and respond to adherence patterns in real-time.     

Effects of Counselling on Adherence to Antiretroviral Treatment Among People with HIV in Estonia: A Randomized Controlled Trial

To assess the efficacy of an education- and strengths-based counselling programme to promote antiretroviral therapy (ART) adherence in a cohort of HIV-infected individuals with high prevalence of injection drug use in Estonia. Parallel-group randomized (1:1) controlled trial (RCT). Adults receiving ART in two clinics were followed for 12 months. The trial compared: (i) an intervention (three sessions) incorporated into routine clinic visits, providing education about HIV, ART, the role of adherence, and tailoring regimen to daily routines using problem-solving skills to address adherence barriers versus (ii) usual care (control). Primary and secondary outcomes were self-reported ART adherence (3-day recall) and viral load (respectively). 519 patients were randomized and 82% completed the study. Recent optimal ART adherence (3-day recall ≥95%) was reported by 75.6% in the intervention group and 72.9% of controls at baseline and 76.7% and 67.5%, respectively, at 12 months (RR 1.14, 95% CI 1.00–1.28; adjusted RR 1.13, 95% CI 1.00–1.27). There was no difference in the proportion of patients with undetectable viral load. At 12 months the intervention group reported significantly higher perceptions of ART necessity versus ART concerns [mean ART necessity-concerns differential: intervention group 1.32 (SD 1.22) vs control group 1.08 (SD 1.12); p = 0.048]. All-cause mortality among study participants was 27.7 per 1000 person years (95% CI 15.6–44.8). A brief, clinic-based adherence intervention alone may assist with adherence but lacks impact on viral load at 12 months.     

Use of electronic reminder devices to improve adherence to antiretroviral therapy: a systematic review

Adherence to prescribed antiretroviral therapy (ART) is one of the strongest predictors of progression to AIDS and death among people living with HIV/AIDS. Incorrect or inconsistent adherence to ART compromises the effectiveness of medications in achieving viral suppression. The objective of this review is to systematically and critically appraise existing evidence on the use of electronic reminder devices (ERDs) to improve adherence to ART among people living with HIV/AIDS. Twelve electronic databases not limited by language or nationality were systematically searched using a combination of relevant search criteria through early August 2007. Primary outcomes of interest were level of adherence and virologic or immunologic response. Ten intervention studies, 5 qualitative studies, and 6 unpublished studies presented in conference abstracts were included. Methodological limitations across the 15 published studies precluded meta-analysis. Evidence that patient adherence to ART was significantly improved with the use of an ERD was reported in 4 of the 8 included studies that examined ERD use as a stand-alone adherence strategy. Patient satisfaction with devices was noted across studies, and conflicting evidence of improved virological and immunological outcomes was reported in the two studies that included such measures. The authors conclude that there is a lack of definitive data resulting in insufficient evidence about the effectiveness of ERDs as strategies for improving patient adherence to antiretroviral medications. Further and more rigorous research is warranted.     

Real-Time Electronic Adherence Monitoring is Feasible,Comparable to Unannounced Pill Counts,and Acceptable

Second generation electronic medication adherence monitors provide real-time data on pill bottle opening behavior. Feasibility, validity, and acceptability, however, have not been established. Med-eMonitor is a multi-compartment adherence device with reminder and education capacity that transmits data through a telephone connection. Monthly adherence levels were measured for 52 participants over approximately 3 months using the Med-eMonitor (unadjusted and adjusted for participant confirmed dosing) and unannounced pill counts. HIV RNA was assessed before and after the 3-month period. Acceptability of Med-eMonitor was determined. Over 92% of Med-eMonitor data was transmitted daily. Unannounced pill counts significantly correlated with adjusted Med-eMonitor adherence (r = 0.29, P = 0.04). HIV RNA significantly correlated with unannounced pill counts (r = −0.34, P = 0.02), and trended toward a significant correlation with unadjusted Med-eMonitor adherence (r = −0.26; P = 0.07). Most, but not all, participants liked using the Med-eMonitor. Med-eMonitor allows for real-time adherence monitoring and potentially intervention, which may be critical for prolonging treatment success.     

Understanding Patterns of Social Support and Their Relationship to an ART Adherence Intervention Among Adults in Rural Southwestern Uganda

SMS is a widely used technology globally and may also improve ART adherence, yet SMS notifications to social supporters following real-time detection of missed doses showed no clear benefit in a recent pilot trial. We examine the demographic and social-cultural dynamics that may explain this finding. In the trial, 63 HIV-positive individuals initiating ART received a real-time adherence monitor and were randomized to two types of SMS reminder interventions versus a control (no SMS). SMS notifications were also sent to 45 patient-identified social supporters for sustained adherence lapses. Like participants, social supporters were interviewed at enrollment, following their matched participant’s adherence lapse and at exit. Social supporters with regular income (RR = 0.27, P = 0.001) were significantly associated with fewer adherence lapses. Instrumental support was associated with fewer adherence lapses only among social supporters who were food secure (RR = 0.58, P = 0.003). Qualitative interview data revealed diverse and complex economic and relationship dynamics, affecting social support. Resource availability in emotionally positive relationships seemingly facilitated helpful support, while limited resources prevented active provision of support for many. Effective social support appeared subject to social supporters’ food security, economic stability and a well-functioning social network dependent on trust and supportive disclosure.     

Optimizing Pre-Exposure Antiretroviral Prophylaxis Adherence in Men Who Have Sex with Men: Results of a Pilot Randomized Controlled Trial of “Life-Steps for PrEP”

Antiretroviral pre-exposure prophylaxis (PrEP) has been demonstrated to decrease HIV acquisition in multiple efficacy trials, but medication adherence is critical, and was suboptimal in several studies. Fifty HIV-uninfected at risk men who have sex with men (MSM) were randomized to a cognitive behavioral intervention condition or a time and session-matched comparison counseling intervention. The experimental intervention entailed four nurse-delivered initial and two booster sessions based on Life-Steps, an ART treatment adherence intervention. The comparison condition provided information and supportive counseling. The primary analyses compared adherence (Wisepill and tenofovir plasma levels) at 3 and 6 months. Fifty-eight MSM were screened to enroll 50 participants. Median age was 38.2 years old, 86% were white; 64% had completed college. Wisepill adherence was high in both groups, and not statistically different. Plasma tenofovir levels were significantly higher in the intervention group at 6 months using mean substitution analysis (i.e., computing missing variables) (p = 0.037), however, in the completer analyses (i.e., using only those completing all study visits), there were no statistically significant differences between randomization conditions. Medication adherence was high across a cognitive-behavioral (Life-Steps) and time-matched counseling intervention for PrEP adherence, with some evidence suggesting superiority of Life-Steps in this pilot RCT. Further evaluation in a fully powered efficacy trial is warranted to assess the robustness of this intervention.     

Acceptability and challenges of rapid ART initiation among pregnant women in a pilot programme,Cape Town,South Africa

Maternal antiretroviral therapy (ART) is a critical intervention in the prevention-of-mother-to child transmission (PMTCT) of HIV. In South Africa, many HIV-infected pregnant women commence ART late in pregnancy, and as a result, the duration of ART prior to delivery is often insufficient to prevent vertical transmission. To address this, we designed an intervention for the rapid initiation of ART in pregnancy (RAP), where patient's ART preparation occurred during rather than before treatment commencement. Here we report on the acceptability and the challenges of the RAP programme. We conducted 7 key informant and 27 semi-structured interviews with RAP participants. Participants were purposefully selected based on ART-eligibility and stage in the pregnancy to post-partum continuum. Interviews were conducted in participants' home language by trained fieldworkers, with key informant interviews conducted by the study investigators. The data were analysed using a framework analysis approach. Rapid initiation in pregnancy was acceptable to the majority of programme participants and protection of the woman's unborn child was the primary motivation for starting treatment. The key barrier was the limited time to accept the dual challenges of being diagnosed HIV-positive and eligible for life-long ART. Truncated time also limited the opportunity for disclosure to others. Despite these and other barriers, most women found the benefits of rapid ART commencement outweighed the challenges, with 91% of women initiated onto ART starting the same day treatment eligibility was determined. Many participants and key informants identified the importance of counseling and the need to make an informed, independent choice on the timing of ART initiation, based on individual circumstances. Acceptance of ART-eligibility improved with time on the programme, however, as women's principal reason for initiating ART was protection of the unborn child, monitoring and supporting adherence during the post-partum period will be critical.     

Exploring ART Intake Scenes in a Human Rights-Based Intervention to Improve Adherence: A Randomized Controlled Trial

To assess the effectiveness of a psychosocial individual intervention to improve adherence to ART in a Brazilian reference-center, consenting PLHIV with viral load >50 copies/ml were selected. After 4 weeks of MEMS cap use, participants were randomized into an intervention group (IG) (n = 64) or control group (CG) (n = 57). CG received usual care only. The IG participated in a human rights-based intervention approach entailing four dialogical meetings focused on medication intake scenes. Comparison between IG and CG revealed no statistically significant difference in adherence measured at weeks 8, 12, 16, 20 and 24. Viral load (VL) decreased in both groups (p < 0.0001) with no significant difference between study groups. The lower number of eligible patients than expected underpowered the study. Ongoing qualitative analysis should provide deeper understanding of the trial results. NIH Clinical Trials: NCTOO716040.     

Counseling for improving adherence to antiretroviral treatment: a systematic review

One-on-one counseling can be an effective strategy to improve patient adherence to HIV treatment. The aim of this systematic review is to examine articles with one-on-one counseling-based interventions, review their components and effectiveness in improving ART adherence. A systematic review, using the following criteria was performed: (i) experimental studies; (ii) published in Spanish, English or Portuguese; (iii) with interventions consisting primarily of counseling; (iv) adherence as the main outcome; (v) published between 2005 and 2016; (vi) targeted 18 to 60 year old, independent of gender or sexual identity. The author reviewed bibliographic databases. Articles were analyzed according to the type of study, type of intervention, period of intervention, theoretical basis for intervention, time used in each counseling session and its outcomes. A total of 1790 records were identified. Nine studies were selected for the review, these applied different types of individual counseling interventions and were guided by different theoretical frameworks. Counseling was applied lasting between 4 to 18 months and these were supervised through three to six sessions over the study period. Individual counseling sessions lasted from 7.5 to 90 minutes (Me. 37.5). Six studies demonstrated significant improvement in treatment. Counseling is effective in improving adherence to ART, but methods vary. Face-to-face and computer counseling showed efficacy in improving the adherence, but not the telephone counseling. More evidence that can determine a basic counseling model without losing the individualized intervention for people with HIV is required.     

Improved adherence with contingency management

Contingency management (CM) based interventions that reinforce adherence to prescribed medications have shown promise in a variety of disadvantaged populations. Fifty-six participants with histories of illicit substance use who were prescribed antiretroviral medication but evidenced suboptimal adherence during a baseline assessment were randomly assigned to 16 weeks of weekly CM-based counseling or supportive counseling, followed by 16 additional weeks of data collection and adherence feedback to providers. The CM intervention involved review of data generated by electronic pill-bottle caps that record bottle opening (MEMS) and brief substance abuse counseling. CM participants were reinforced for MEMS-measured adherence with drawings from a bowl for prizes and bonus drawings for consecutive weeks of perfect adherence. Potential total earnings averaged $800. Mean MEMS-measured adherence to the reinforced medication increased from 61% at baseline to 76% during the 16-week treatment phase and was significantly increased relative to the supportive counseling group (p = 0.01). Furthermore, mean log-transformed viral load was significantly lower in the CM group. However, by the end of the 16-week follow-up phase, differences between groups in adherence and viral load were no longer significantly different. Proportions of positive urine toxicology tests did not differ significantly between the two groups at any phase. A brief CM-based intervention was associated with significantly higher adherence and lower viral loads. Future studies should evaluate methods to extend effects for longer term benefits.     

A qualitative study on alcohol consumption and HIV treatment adherence among men living with HIV in Ugandan fishing communities

Ugandan fishing communities are dually burdened with high rates of HIV and alcohol use. This qualitative study explores context and motivation of alcohol consumption, and alcohol's effect on antiretroviral treatment (ART) adherence, among male fisherfolk living with HIV in Wakiso District, Uganda. We conducted in-depth semi-structured interviews with 30 men in HIV care and on ART, and used a thematic analysis approach for analysis. Alcohol use was identified as a major barrier to ART adherence through cognitive impairment and the intentional skipping of doses when drinking. Men reportedly reduced their drinking since HIV diagnosis – motivated by counseling received from providers and a newfound desire to live a healthy lifestyle. However, social, occupational, and stress-related influences that make alcohol reduction difficult were identified. Our findings suggest alcohol use may pose a challenge to ART adherence for fishermen living with HIV – and has implications for the tailoring of screening and brief intervention for alcohol reduction in HIV care for this population.     

Qualitative and quantitative assessments of HAART adherence of substance-abusing women

This study was set up to examine factors affecting adherence to highly active antiretroviral therapy (HAART) by substance abusing women and to conduct a pilot study of a reminder device intervention. Three focus groups totaling 24 HIV-positive women developed priority lists of issues affecting adherence. Another group of 24 HIV-positive women received a timer-reminder with structured interviews on adherence at baseline and two monthly follow up intervals. Focus groups described key barriers to HAART adherence as substance abuse, forgetting, feeling ill, others' negative attitudes, obtaining refills and confidentiality. Primary disadvantages to HAART were side effects, pill-taking schedule and burden of taking medications. Facilitators included reminders (e.g. pill boxes) and spirituality. After receiving the reminder, missing a dose was less common (p < 0.05) due to sleeping through dose, being busy and feeling too good while a favourable trend (p = 0.07) was seen for change in daily routine and having too many pills to take. Although well accepted, the reminder did not affect the proportion missing a dose in the past two weeks: baseline (33%), first follow-up (30%) and second follow-up (30%). Forgetting to take HAART was only one of many cited barriers to adherence in these HIV-positive women; well-received reminder devices did not affect adherence. To improve substance-abusing women's adherence, multidimensional interventions are warranted.     

Perceptions About the Acceptability of Assessments of HIV Medication Adherence in Lilongwe, Malawi and Chennai, India

Little research exists on acceptability issues related to assessments of adherence to ART in resource-poor settings. To help prepare for two large-scale, multisite ART intervention trials, this qualitative study of individuals in Chennai, India (49 men, 11 women; 33 taking ART, 27 not) and Lilongwe, Malawi (5 men, 5 women, all taking ART) examined potential limitations of different types of adherence assessments: an adherence questionnaire, a pill diary, a pillbox, an electronic pill cap, and a medication punch card. Many participants reported that the various assessments would be acceptable. Potential limitations included issues surrounding literacy, the desire to appease one’s medical provider, privacy and stigma, and “cheating.” These potential limitations are similar to the limitations of these assessments in Western settings. However, the data highlight the need to consider individual patient level concerns when assessing ART adherence in different cultural settings. Innovative ways of monitoring adherence while maintaining standardization across sites are required in multisite trials.