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

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.

Fig. 1

Study design

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

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