Feasibility of a pragmatic randomized adaptive clinical trial to evaluate a brief negotiational interview for harmful and hazardous alcohol use in Moshi, Tanzania.

INTRODUCTION: Low-resourced settings often lack personnel and infrastructure for alcohol use disorder treatment. We culturally adapted a Brief Negotiational Interview (BNI) for Emergency Department injury patients, the "Punguza Pombe Kwa Afya Yako (PPKAY)" ("Reduce Alcohol For Your Health") in Tanzania. This study aimed to evaluate the feasibility of a pragmatic randomized adaptive controlled trial of the PPKAY intervention. MATERIALS AND METHODS: This feasibility trial piloted a single-blind, parallel, adaptive, and multi-stage, block-randomized controlled trial, which will subsequently be used to determine the most effective intervention, with or without text message booster, to reduce alcohol use among injury patients. We reported our feasibility pilot study using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, with recruitment and retention rates being our primary and secondary outcomes. We enrolled adult patients seeking care for an acute injury at the Kilimanjaro Christian Medical Center in Tanzania if they (1) exhibited an Alcohol Use Disorder Identification Test (AUDIT) ≥8, (2) disclosed alcohol use prior to injury, or (3) had a breathalyzer ≥0.0 on arrival. Intervention arms were usual care (UC), PPKAY, PPKAY with standard text booster, or a PPKAY with a personalized text booster. RESULTS: Overall, 181 patients were screened and 75 enrolled with 80% 6-week, 82.7% 3-month and 84% 6-month follow-up rates showing appropriate Reach and retention. Adoption measures showed an overwhelmingly positive patient acceptance with 100% of patients perceiving a positive impact on their behavior. The Implementation and trial processes were performed with high rates of PPKAY fidelity (76%) and SMS delivery (74%). Intervention nurses believed Maintenance and sustainability of this 30-minute, low-cost intervention and adaptive clinical trial were feasible. CONCLUSIONS: Our intervention and trial design are feasible and acceptable, have evidence of good fidelity, and did not show problematic deviations in protocol. Results suggest support for undertaking a full trial to evaluate the effectiveness of the PPKAY, a nurse-driven BNI in a low-income country. TRIAL REGISTRATION: Trial registration number NCT02828267. https://classic.clinicaltrials.gov/ct2/show/NCT02828267.

Effect of a customized digital adherence tool on retention in care and adherence to antiretroviral treatment in breastfeeding women, children and adolescents living with HIV in Tanzania: a mixed-methods study followed by clinical trials.

BACKGROUND: Adherence to antiretroviral (ARV) treatment for HIV infection is challenging because of many factors. The World Health Organization (WHO) has recommended using digital adherence technologies (DATs). However, there is limited evidence on how DATs improve adherence. Wisepill® is an internet-enabled medication dispenser found feasible and acceptable in several studies. However, limited evidence is available on its effectiveness in improving ART adherence, specifically among children and adolescents. Furthermore, DATs are often developed without involving the target groups. We propose a two-stage project consisting of a formative study to customize an existing Wisepill DAT intervention and a randomized clinical trial to investigate the effectiveness of DAT combined with reminder cues and tailored feedback on adherence to ARV treatment among children and adolescents living with HIV and retention in care among breastfeeding women living with HIV in Kilimanjaro and Arusha Region, Tanzania. METHODS: We will conduct a formative mixed-methods study and three sub-trials in Kilimanjaro and Arusha Regions among (1) children aged 0-14 years and their caregivers, (2) adolescents aged 15-19 years and (3) breastfeeding women and their HIV-negative infants. In the formative study, we will collect and analyse data on needs and contents for DATs, including the contents of short message service (SMS) texts and tailored feedback. The results will inform the customization of the DAT to be tested in the sub-trials. In the trials, participants will be randomized in the intervention arm, where the DAT will be implemented or the control arm, where standard care will be followed. Participants in the intervention arm will take their medication from the Wisepill box and receive daily reminder texts and tailored feedback during clinic visits. DISCUSSION: If the intervention improves adherence to ART and the devices are acceptable, accurate and sustainable, the intervention can be scaled up within the National Aids Control Programmes. TRIAL REGISTRATION: PACTR202301844164954, date 27 January 2023.

Predicting viral load suppression by self-reported adherence, pharmacy refill counts and real time medication monitoring among people living with HIV in Tanzania.

INTRODUCTION: Monitoring of adherence to antiretroviral treatment (ART) is of utmost importance to prevent treatment failure. Several measures to monitor adherence have been applied in low-resource settings and they all have pros and cons. Our objective was to examine whether any of the following adherence measures is a better predictor of participants' viral load suppression: (1) self-report, (2) pharmacy refill count, (3) Real Time Medication Monitoring (RTMM), (4) a combination of self-report and pharmacy refill count or (5) all three adherence assessment methods combined. METHODOLOGY: This was a post-hoc analysis of data from our 48-week REMIND-HIV randomized controlled trial in which adherence to ART was measured using self-report, pharmacy refill counts and RTMM among ART-experienced adults living with HIV subjectively judged to be nonadherent to ART. For each adherence measure, we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for predicting virological failure defined as a viral load (VL) of > 20 copies/mL. To determine at which percentage of adherence the prediction was strongest, we evaluated adherence cut-offs of 80%, 85%, 90%, 95% and 100% using receiver operating characteristic (ROC) curves. VL data were obtained after 48 weeks of follow-up in the trial. RESULTS: A total of 233 people living with HIV (PLHIV) were included in this analysis. When comparing the ability of self-reported adherence with pharmacy refill count and RTMM adherence to predict viral load > 20 copies/ml, self-reported adherence had the lowest sensitivity, ranging from 6 to 17%, but the highest specificity, ranging from 100 to 86%, depending on cut-off values from 80 to 100%. Area under the ROC curves (AUC) were 0.54 for RTMM, 0.56 for pharmacy refill count and 0.52 for self-report, indicating low discriminatory capacity for each of the adherence measures. When we combined the self-report and pharmacy refill count measures, sensitivity increased, ranging from 28 to 57% but specificity decreased, ranging from 83 to 53%. When all three measures were combined, we observed the highest value of sensitivity, ranging from 46 to 92%, and PPV, ranging from 32 to 36%, at high cut-offs ranging from 80 to 100%. Upon combination of three adherence measures, the AUC increased to 0.59. CONCLUSION: Our results show that adherence assessed exclusively by self-report, pharmacy refill count or RTMM were insufficiently sensitive to predict virologic failure. Sensitivity markedly improved by combining all three measures, but the practical feasibility of such an approach would need to be studied.

Effect of Digital Adherence Tools on Adherence to Antiretroviral Treatment Among Adults Living With HIV in Kilimanjaro, Tanzania: A Randomized Controlled Trial.

BACKGROUND: Lifelong adherence to antiretroviral treatment remains challenging for people living with HIV (PLHIV). The aim of this study was to investigate whether any of 2 digital adherence tools could improve adherence among PLHIV in Kilimanjaro, Tanzania. METHODS: We performed a parallel 3-arm, nonblinded, randomized controlled trial with 1:1:1 allocation. We included adults aged between 18 and 65 years, living in Kilimanjaro region, and who were on antiretroviral treatment for at least 6 months. Their adherence, as judged by the study nurses, had to be suboptimal. In one arm, participants received reminder short message service (SMS) texts, followed by a question SMS. In the second arm, participants received a real-time medication monitoring (RTMM) device (Wisepill) with SMS reminders. In the third arm, participants received standard care only. The primary outcome of mean adherence over 48 weeks was compared between arms using between-group t tests in a modified intention-to-treat analysis. RESULTS: In each arm, we randomized 83 participants: data of 82 participants in the RTMM arm, 80 in the SMS arm, and 81 in the standard care arm were analyzed. The average (over 48 weeks) adherence in the SMS, RTMM, and control arms was 89.6%, 90.6%, and 87.9% for pharmacy refill; 95.9%, 95.0%, and 95.2% for self-report in the past week; and 97.5%, 96.6%, and 96.9% for self-report in the past month, respectively (P values not statistically significant). CONCLUSIONS: Receiving reminder SMS or RTMM combined with feedback about adherence levels and discussion of strategies to overcome barriers to adherence did not improve adherence to treatment and treatment outcome in PLHIV. CLINICAL TRIAL NUMBER: PACTR201712002844286.

Feasibility of SMS to remind pregnant and breastfeeding women living with HIV to take antiretroviral treatment in Kilimanjaro region, Tanzania: a pilot study.

BACKGROUND: Pregnant and breastfeeding Women Living with HIV (WLHIV) often have difficulties in reaching adequate levels of adherence (>95%) to Antiretroviral treatment. "Forgetting" is the most commonly mentioned reason. Sending reminders via SMS is expected to improve adherence. We conducted a pilot study to investigate acceptability, user experience and technical feasibility of sending reminder-SMS to WLHIV. METHODS: This was a 6-months observational pilot-study among WLHIV attending antenatal and postnatal care at Kilimanjaro Christian Medical Centre in Moshi, Tanzania. Women received a reminder-SMS 30 minutes before usual time of intake. One hour later, they received an SMS asking whether they took medication to which they could reply with 'Yes' or 'No'. Messages were sent 3 times a week on randomly chosen days to prevent reliance on daily messages. We calculated the percentage of number of SMS delivered, failed to be delivered, and replied to. We analysed feedback from exit-interviews about experience with the SMS-reminders. RESULTS: 25 women were enrolled (age 18-45), 2 were lost to follow up. 5,054 messages were sent of which 53 failed to be delivered (1%). 1,880 SMS were sent with a question if medication was taken; 1,012 (54%) messages were replied to, of which 1,003 (99%) were replied with 'YES' and closely to 'YES', and a total of 9 (1%) with 'NO' and 'closely to NO'. 868 messages (46%) were not responded to due to either dropout, change of phone number, loss of phone or network failure. Results from 18 interviews showed that 16 (89%) women were satisfied with SMS reminders. 2 (11%) were concerned about unwanted disclosure because of the content 'don't forget to take medication' and one reported other privacy issues (6%). 3 (17%) women experienced stigma. CONCLUSION: 99%of SMS being delivered indicates that SMS reminders in this resource-limited setting are technically feasible. However, concerns regarding privacy were noted, specifically the risk of unwanted disclosure and the experience of stigma. Participants indicated that being made aware of their adherence, motivated them to adhere better. However, personalised and more neutral content of the SMS might be a way to improving the intervention.

Implementation and effectiveness of evriMED with short messages service (SMS) reminders and tailored feedback compared to standard care on adherence to treatment among tuberculosis patients in Kilimanjaro, Tanzania: proposal for a cluster randomized controlled trial.

BACKGROUND: Adherence to tuberculosis (TB) treatment is challenging because of many factors. The World Health Organization has recommended the use of digital adherence monitoring technologies in its End TB Strategy. However, evidence on improving adherence is limited. EvriMED is a real-time medication-monitoring device which was found to be feasible and acceptable in a few studies in Asia. In Tanzania, however, there may be challenges in implementing evriMED due to stigmatization, network and power access, accuracy, and cost effectiveness, which may have implications for treatment outcome. We propose a pragmatic cluster randomized trial to investigate the effectiveness of evriMED with reminder cues and tailored feedback on adherence to TB treatment in Kilimanjaro, Tanzania. METHODS/DESIGN: We will create clusters in Kilimanjaro based on level of health care facility. Clusters will be randomized in an intervention arm, where evriMED will be implemented, or a control arm, where standard practice directly observed treatment will be followed. TB patients in intervention clusters will take their medication from the evriMED pillbox and receive tailored feedback. We will use the 'Stages of Change' model, which assumes that a person has to go through the stages of pre-contemplation, contemplation, preparation, action, and evaluation to change behavior for tailored feedback on adherence reports from the device. DISCUSSION: If the intervention shows a significant effect on adherence and the devices are accepted, accurate, and sustainable, the intervention can be scaled up within the National Tuberculosis Programmes. TRIAL REGISTRATION: Pan African Clinical Trials Registry, PACTR201811755733759 . Registered on 8 November 2018.

Feasibility of Real Time Medication Monitoring Among HIV Infected and TB Patients in a Resource-Limited Setting.

HIV infected and tuberculosis (TB) patients need high levels of treatment adherence to achieve optimal treatment outcomes. We conducted a pilot-study on real time medication monitoring (RTMM) in a resource-limited setting. We enrolled five HIV infected and five TB patients from Kilimanjaro, Tanzania. They took their medication using RTMM. When the device was not opened on time, patients received a reminder SMS. After 3 months, we interviewed patients. Six patients (60 %) reached adherence of >95 %. Nine-hundred-twenty-two of 1104 intakes (84 %) were on time. Five-hundred reminders (45 %) were sent, of which 202 (40 %) were incorrect, because of an unstable mobile network. Nine patients found the device helpful and nine mentioned it keeps medication safe. Six patients reported that the size was too big. Five patients mentioned they received incorrect reminders. The device is considered useful in Kilimanjaro. Optimization of the device should consider network connectivity and the size of the device.