학술논문
Adherence Measured Using Electronic Dose Monitoring is Associated with Emergent Antiretroviral Resistance and Poor Outcomes in People with Human Immunodeficiency Virus/AIDS and Multidrug-Resistant Tuberculosis.
Document Type
Article
Author
Source
Subject
*CLINICAL drug trials
*HIV infections
*DRUG delivery systems
*NEVIRAPINE
*STATISTICS
*SEQUENCE analysis
*GENETIC mutation
*SCIENTIFIC observation
*CONFIDENCE intervals
*SUBSTANCE abuse
*VIRAL load
*BLOOD plasma
*MULTIPLE regression analysis
*AGE distribution
*ANTIRETROVIRAL agents
*RNA
*ACQUISITION of data
*TREATMENT effectiveness
*RISK assessment
*SEX distribution
*ANTITUBERCULAR agents
*DRUG monitoring
*MULTIDRUG resistance
*PUBLIC hospitals
*GENOMES
*DESCRIPTIVE statistics
*QUESTIONNAIRES
*MEDICAL records
*PATIENT compliance
*STATISTICAL models
*POLYMERASE chain reaction
*ANALYTICAL chemistry techniques
*DATA analysis software
*LOGISTIC regression analysis
*ODDS ratio
*BODY mass index
*AIDS-related opportunistic infections
*LONGITUDINAL method
*LOPINAVIR-ritonavir
*PROPORTIONAL hazards models
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Language
ISSN
1058-4838
Abstract
Background Medication adherence is known to challenge treatment of human immunodeficiency virus (HIV)/AIDS and multidrug-resistant tuberculosis (MDR-TB). We hypothesized that adherence using electronic dose monitoring (EDM) would identify an antiretroviral therapy (ART) adherence threshold for emergent ART resistance and predict treatment outcomes in patients with MDR-TB and HIV on ART and bedaquiline-containing TB regimens. Methods A prospective cohort of adults with MDR-TB and HIV on ART and initiating MDR-TB treatment with bedaquiline were enrolled at a public hospital in KwaZulu-Natal, South Africa (PRAXIS Study). Participants received separate EDM devices that measure adherence to bedaquiline and ART (nevirapine or lopinavir/ritonavir). Adherence was calculated cumulatively over 6 months. Participants were followed through completion of MDR-TB treatment. HIV genome sequencing was performed at baseline and 2 and 6 months on samples with HIV RNA ≥1000 copies/mL. Results From November 2016 through February 2018, 198 persons with MDR-TB and HIV were enrolled and followed (median, 17.2 months; interquartile range, 12.2–19.6). Eleven percent had baseline ART resistance mutations, and 7.5% developed emergent ART resistance at 6 months. ART adherence was independently associated with ART resistance and mortality. Modeling identified a significant (P <.001), linear association between ART adherence and emergent resistance, suggesting a strong association without a specific threshold. Conclusions Our findings highlight the need for ART resistance testing, especially in patients with MDR-TB and HIV, which is currently not the standard of care in resource-limited settings. Despite short follow-up duration, reduced ART adherence was significantly associated with emergent resistance and increased mortality. Clinical Trials Registration NCT03162107. [ABSTRACT FROM AUTHOR]