Electronic Dose Monitoring Identifies a High-Risk Subpopulation in the Treatment of Drug-resistant Tuberculosis and Human Immunodeficiency Virus

Abstract

Background: In generalized drug-resistant tuberculosis (DR-TB) human immunodeficiency virus (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 patients with DR-TB HIV 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 patients with DR-TB HIV were identified as dual-adherence challenged. In a multivariate model including baseline characteristics, only receiving a disability grant was significantly associated with dual nonadherence at 6 months. Mixed-methods identified treatment barriers including alcohol abuse, family conflicts, and mental health issues. Compared with 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 than more adherent patients.

Conclusions: EDM empirically identified a subpopulation of patients with DR-TB HIV with dual-adherence challenges early in treatment. Mixed-methods revealed intense psychosocial, behavioral, and structural barriers to care in this subpopulation. Our data support developing differential, patient-centered, adherence support interventions focused on psychosocial and structural challenges for subpopulations of at-risk DR-TB HIV patients.

Keywords: South Africa; adherence; drug-resistant TB/HIV; mixed-methods; person-centered care.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Enrollment flowchart showing the number of patients screened, enrolled, and included in analysis. *One patient died 11 days after enrollment and had not initiated treatment; 1 patient was enrolled but subsequently found to be ineligible. Abbreviations: ART, antiretroviral therapy; DR-TB, drug-resistant tuberculosis; HIV, human immunodeficiency virus; TB, tuberculosis.

Figure 2.

Six-month cumulative dual adherence to BDQ and ART as measured by an electronic dose monitoring device with low adherence defined as less than 85% (red line) and severe adherence-challenged patients defined as low adherence to both ART and BDQ (blue box). Abbreviations: ART, antiretroviral therapy; BDQ, bedaquiline.

Figure 3.

Kaplan-Meier curve demonstrating survival in patients with MDR-TB and HIV stratified by measured dual adherence to antiretroviral therapy and bedaquiline (>85%) compared with dual nonadherence (P < .001). Abbreviations: HIV, human immunodeficiency virus; MDR, multidrug-resistant; TB, tuberculosis.