Pilot evaluation of a second-generation electronic pill box for adherence to Bedaquiline and antiretroviral therapy in drug-resistant TB/HIV co-infected patients in KwaZulu-Natal, South Africa

N Bionghi, A Daftary, B Maharaj, Z Msibi, K R Amico, G Friedland, C Orrell, N Padayatchi, M R O'Donnell, N Bionghi, A Daftary, B Maharaj, Z Msibi, K R Amico, G Friedland, C Orrell, N Padayatchi, M R O'Donnell

Abstract

Background: The introduction of Bedaquiline, the first new antimycobacterial drug in over 40 years, has highlighted the critical importance of medication adherence in drug-resistant tuberculosis (DR-TB) treatment to prevent amplified drug-resistance and derive sustained benefit. Real-time electronic dose monitoring (EDM) accurately measures adherence and allows for titration of adherence support for anti-retroviral therapy (ART). The goal of this study was to evaluate the accuracy and acceptability of a next-generation electronic pillbox (Wisepill RT2000) for Bedaquiline-containing TB regimens.

Methods: Eligible patients were DR-TB/HIV co-infected adults hospitalized for the initiation of Bedaquiline-containing treatment regimens in KwaZulu-Natal, South Africa. A one-way crossover design was used to evaluate levels of adherence and patient acceptance of EDM. Each patient was given a Wisepill device which was filled with ART, Levofloxacin or Bedaquiline over three consecutive weeks. Medication adherence was measured using Wisepill counts, patient-reported seven-day recall, and weekly pill count. An open-ended qualitative questionnaire at the end of the study evaluated participant acceptability of the Wisepill device.

Results: We enrolled 21 DR-TB/HIV co-infected inpatients admitted for the initiation of Bedaquiline from August through September 2016. In aggregate patients were similarly adherent to Bedaquiline (100%) compared to Levofloxacin (100%) and ART (98.9%) by pill count. Wisepill was more sensitive (100%) compared to seven-day recall (0%) in detecting non-adherence events (p = 0.02). Patients reported positive experiences with Wisepill and expressed willingness to use the device during a full course of DR-TB treatment. There were no concerns about stigma, confidentiality, or remote monitoring.

Conclusion: In this pilot study patients were highly adherent to Bedaquiline by all adherence measures. However, there was lower adherence to ART by pill count and Wisepill suggesting a possible challenge for adherence with ART. The use of EDM identified significantly more missed doses than seven-day recall. Wisepill was highly acceptable to DR-TB/HIV patients in South Africa, and is a promising modality to support and monitor medication adherence in complex treatment regimens.

Keywords: Bedaquiline; Drug-resistant tuberculosis; Electronic pillbox; HIV; Real-time monitoring.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Institutional Review Boards at Columbia University Medical Center and the Biomedical Research Ethics Committee at the University of KwaZulu-Natal in South Africa. Written informed consent was obtained from all patients in either isiZulu or English.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study design
Fig. 2
Fig. 2
Wisepill device functions. The Wisepill device transmits a wireless signal to the Wisepill web server when device is opened. Device openings are recorded in real-time on the online dashboard and available for users to view. If the SMS reminder service is used, the patients/caregivers may receive message reminders when a medication dose is due or overdue. Image obtained from Wisepill Technologies with permission
Fig. 3
Fig. 3
Example of participant intakes reported on Wisepill online dashboard. Example online dashboard display of device openings for a single participant during the three-week study period. The first day of the next medication week is shown with a dotted line. Medication dosing was self-administered. Blue diamonds indicate extra Wisepill device openings for weekly pill count or reloading medications. Red circles indicate a missed expected Wisepill device opening. *Nevirapine (NVP): 200 mg BID; Aluvia: Lopinavir 200 mg – 50 mg Ritonavir BID

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