Forgetting to Take Medication, Treatment Adherence and Their Relationship with Viral Load Suppression Among People Living with HIV in the Kilimanjaro Region, Tanzania.

Background: Antiretroviral therapy (ART) adherence is crucial for virological suppression and positive treatment outcomes among people living with HIV (PLHIV), but remains a challenge in ensuring patients achieve and sustain viral load suppression. Despite the recommended use of digital tools medications uptake reminders, the contribution of forgetting to take medication is unknown. This study investigated the contribution of forgetting to take medication on the total missed medication and its effects on detectable viral load (VL). Methods: This mixed-method research was conducted among children, adolescents, pregnant, and breastfeeding women living with HIV on ART in northern Tanzania. Forgetting to take medication constituted reporting to have missed medication due to forgetfulness. A multivariable logistic regression model was used to estimate the adjusted odds ratio (AOR) with a 95% confidence interval (CI) to determine the contribution of forgetting medication intakes on total missed medication and other factors associated with having a detectable VL. Results: Of 427 respondents, 33.3% were children, 33.4% adolescents, and 33.3% pregnant and breastfeeding women, whose median age (interquartile range) was 9 (7-12), 18 (16-18), and 31 (27-36) years, respectively. Ninety-two (22.3%) reported missing medication over the past month, of which 72 (17.9%) was due to forgetting. Forgetting to take medication (AOR: 1.75 95% CI: 1.01-3.06) and being on second-line regimen (AOR: 2.89 95% CI: 1.50-5.55) increased the chances of a detectable VL, while females had lower chances of detectable VL (AOR: 0.62 95% CI: 0.41-0.98). The themes on the reasons for forgetting to take medication from qualitative results included being busy with work and the importance of reminders. Conclusion: Forgetting to take medication is common among PLHIV and an important predictor of a detectable VL. This calls for the use of automated short message services (SMS) reminders or Digital Adherence Tools with reminders to improve and promote good ART adherence among PLHIV.

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.

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.

Returning of antiretroviral medication dispensed over a period of 8 months suggests non-adherence despite full adherence according to real time medication monitoring.

Real-time medication monitoring (RTMM) may potentially enhance adherence to antiretroviral treatment (ART). We describe a participant in an ongoing trial who, shortly after completing trial participation, died of cryptococcal meningitis despite high levels of adherence according to self-report, pill-counts and RTMM (> 99%). However, she evidenced consistently high HIV viral load throughout the 48-week study follow-up. Subsequently, her relatives unsolicitedly returned eight months' dispensed ART medication that she was supposed to have taken. This brief report illustrates the challenges of adherence measurements including RTMM, and reinforces the need to combine adherence assessments with viral load monitoring in HIV care.

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.

HIV stigma and depressive symptoms are related to adherence and virological response to antiretroviral treatment among immigrant and indigenous HIV infected patients.

We compared adherence to cART and virological response between indigenous and immigrant HIV-infected patients in the Netherlands, and investigated if a possible difference was related to a difference in the psychosocial variables: HIV-stigma, quality-of-life, depression and beliefs about medications. Psychosocial variables were assessed using validated questionnaires administered during a face-to-face interview. Adherence was assessed trough pharmacy-refill monitoring. We assessed associations between psychosocial variables and non-adherence and having detectable plasma viral load using logistic regression analyses. Two-hundred-two patients participated of whom 112 (55%) were immigrants. Viral load was detectable in 6% of indigenous patients and in 15% of the immigrants (P < 0.01). In multivariate analyses, higher HIV-stigma and prior virological failure were associated with non-adherence, and depressive symptoms, prior virological failure and non-adherence with detectable viral load. Our findings suggest that HIV-stigma and depressive symptoms may be targets for interventions aimed at improving adherence and virological response among indigenous and immigrant HIV-infected patients.