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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1489-1496
Number of pages8
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume75
Issue number9
DOIs
StatePublished - Oct 29 2022

Keywords

  • antiretroviral adherence
  • electronic dose monitoring
  • emergent resistance
  • patients with HIV/AIDS and multidrug-resistant tuberculosis
  • South Africa

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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