Title: Adherence measured using electronic dose monitoring is associated with emergent antiretroviral resistance and poor outcomes in patients co-infected with HIV/AIDS and multidrug-resistant tuberculosis
Authors: Bateman M, Wolf A, Chimukangara B, Brust JCM, Lessells R, Amico R, Boodhram R, Singh N, Orrell C, Friedland G, Naidoo K, Padayatchi N, O'Donnell MR.
Journal: Clin Infect Dis.,ciac232. doi: 10.1093/cid/ciac232: (2022)
Background: Medication adherence is known to challenge treatment of HIV/AIDS and multidrug-resistant tuberculosis (MDR-TB). We hypothesized that electronic dose adherence monitoring (EDM) would identify an 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 TB referral hospital in KwaZulu-Natal, South Africa (PRAXIS Study, Clinicaltrials.gov NCT03162107). Participants received separate EDM devices measuring adherence to bedaquiline and ART (nevirapine or lopinavir/ritonavir). Adherence was calculated cumulatively over six months. Participants were followed through completion of MDR-TB treatment. HIV genome sequencing was performed at baseline, 2 and 6 months on samples with HIV RNA ?1000 copies/mL.
Findings: From November 2016 through February 2018, 198 MDR-TB and HIV co-infected participants were enrolled and followed (median 17.2 months, IQR 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 both emergent ART resistance and mortality. Modeling identified a significant (p<0.001), but linear association between ART adherence and emergent resistance, suggesting a strong association without a specific threshold.
Interpretation: Our findings highlight the need for ART resistance testing, especially in MDR-TB HIV co-infected patients, which is currently not standard of care in resource-limited settings. Despite short follow-up duration, reduced ART adherence was significantly associated with emergent resistance and increased mortality.
Citation: Bateman M, Wolf A, Chimukangara B, Brust JCM, Lessells R, Amico R, Boodhram R, Singh N, Orrell C, Friedland G, Naidoo K, Padayatchi N, O'Donnell MR. Adherence measured using electronic dose monitoring is associated with emergent antiretroviral resistance and poor outcomes in patients co-infected with HIV/AIDS and multidrug-resistant tuberculosis Clin Infect Dis.,ciac232. doi: 10.1093/cid/ciac232: (2022).
KRISP has been created by the coordinated effort of the University of KwaZulu-Natal (UKZN), the Technology Innovation Agency (TIA) and the South African Medical Research Countil (SAMRC).