Electronic dose monitoring identifies a high-risk subpopulation in the treatment of drug-resistant tuberculosis and HIV.

BACKGROUND In generalized drug-resistant tuberculosis (DR-TB) HIV epidemics, identifying subpopulations at high risk for treatment failure and loss to care is critically important to improve treatment outcomes and prevent amplification of drug resistance. We hypothesized that an electronic dose-monitoring (EDM) device could empirically identify adherence-challenged patients and that a mixed-methods approach would characterize treatment challenges. METHODS A prospective study of DR-TB HIV patients on antiretroviral therapy (ART) initiating bedaquiline-containing regimens in KwaZulu-Natal, South Africa. Separate EDM devices measured adherence for bedaquiline and ART. Patients with low adherence (<85%) to both bedaquiline and ART were identified as high-risk for poor outcomes. Baseline survey, study visit notes and focus group discussions characterized treatment challenges. RESULTS From December 2016-February 2018, 32 of 198 (16%) enrolled DR-TB HIV patients were identified as dual adherence-challenged. In a multivariate model including baseline characteristics, only receiving a disability grant was significantly associated with dual non-adherence at 6-months. Mixed-methods identified treatment barriers including, alcohol abuse, family conflicts, and mental health issues. Compared to adherent patients, dual-adherence challenged patients struggled to prioritize treatment and lacked support, and dual adherence-challenged patients experienced higher rates of detectable HIV viral load and mortality compared to more adherent patients. CONCLUSION EDM empirically identified a subpopulation of DR-TB HIV patients with dual adherence challenges early in treatment. Mixed-methods revealed intense psychosocial, behavioral, and structural barriers to care in this subpopulation. Our data supports developing differential, patient-centered, adherence support interventions focused on psychosocial and structural challenges for subpopulations of at-risk DR-TB HIV patients.