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

Abstract 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.