1. 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.
- Author
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Bateman, Mark, Wolf, Allison, Chimukangara, Benjamin, Brust, James C M, Lessells, Richard, Amico, Rivet, Boodhram, Resha, Singh, Nalini, Orrell, Catherine, Friedland, Gerald, Naidoo, Kogieleum, Padayatchi, Nesri, and O'Donnell, Max R
- Subjects
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 - 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]
- Published
- 2022
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