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BMC Infect Dis. 2018 Apr 11;18(1):171. doi: 10.1186/s12879-018-3080-2.

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.

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Columbia University College of Physicians and Surgeons, NY, NY, USA.
CAPRISA MRC- HIV-TB Pathogenesis and Treatment Research Unit, Durban, South Africa.
McGill International TB Centre, McGill University, Montreal, Canada.
University of Michigan School of Public Health, Ann Arbor, MI, USA.
Yale School of Medicine, New Haven, CT, USA.
Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.
CAPRISA MRC- HIV-TB Pathogenesis and Treatment Research Unit, Durban, South Africa.
Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, NY, NY, USA.
Department of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, NY, NY, USA.



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.


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.


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.


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.


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

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