ABSTRACT: Improving adherence to combined antiretroviral therapy (cART) can be challenging, especially among vulnerable populations living with HIV. Even where cART is available free of charge, social determinants of health act as barriers to optimal adherence rates. Patient-centered approaches exploiting mobile phone communications (mHealth) have been shown to improve adherence to cART and promote achievement of suppressed HIV plasma viral loads. However, data are scarce on the health care provider (HCP) time commitments and health care costs associated with such interventions. This knowledge is needed to inform policy and programmatic implementation.The purpose of this study was to approximate the resources required and to provide an estimate of the costs associated with running an mHealth intervention program to improve medication adherence in people living with HIV (PLWH).This prospective study of HCP utilization and costs was embedded within a repeated measures effectiveness study of the WelTel short-message service (SMS) mHealth program. The study included 85 vulnerable, nonadherent PLWH in Vancouver, Canada, and resulted in improved medication adherence and HIV plasma viral load among participants. Study participants were provided mobile phones with unlimited texting (where required) and received weekly bidirectional text messages to inquire on their status for one year. A clinic nurse triaged and managed participants' responses, immediately logging all patient interactions by topic, HCP involvement, and time dedicated to addressing issues raised by participants. Interaction costs were determined in Canadian dollars based on HCP type, median salary within our health authority, and their time utilized as part of the intervention.Participant-identified problems within text responses included health-related, social, and logistical issues. Taken together, management of problems required a median of 43 minutes (interquartile range, IQR 17-99) of HCP time per participant per year, for a median yearly cost of Can $36.72 (IQR 15.50-81.60) per participant who responded with at least one problem. The clinic nurse who monitored the texts solved or managed 65% of these issues, and the remaining were referred to a variety of other HCPs. The total intervention costs, including mobile phones, plans, and staffing were a median Can $347.74/highly vulnerable participant per year for all participants or Can $383.18/highly vulnerable participant per year for those who responded with at least one problem.Bidirectional mHealth programs improve HIV care and treatment outcomes for PLWH. Knowledge about the HCP cost associated, here less than Can $50/year, provides stakeholders and decision makers with information relevant to determining the feasibility and sustainability of mHealth programs in a real-world setting.ClinicalTrials.gov NCT02603536; https://clinicaltrials.gov/ct2/show/NCT02603536 (Archived by WebCite at http://www.webcitation.org/70IYqKUjV).