Feasibility, acceptability, safety, tolerability, and changes in alcohol consumption associated with off-label medications for alcohol use disorder among patients with HIV: protocol for an open-label pilot study

Background Alcohol use disorder (AUD) is associated with poorer health outcomes among people with HIV (PWH) including serious interactions with medications. However, we lack treatments that address AUD in the context of HIV and polypharmacy. We describe the protocol for three open-label pilot studies to determine the feasibility, acceptability, safety, tolerability, and potential changes in alcohol consumption associated with the off-label use of medications with potential efficacy for the treatment of AUD – spironolactone, varenicline, and semaglutide – among PWH with AUD and polypharmacy. We hypothesize that off-label use of each of these three medications with a Clinical Pharmacist-delivered behavioral intervention will be feasible, acceptable, safe, tolerable and demonstrate changes in alcohol consumption. Methods Conducted as part of the HIV and Alcohol Research Center focused on Polypharmacy (HARP) activities, we aim to enroll 60 adults (20 participants per pilot study) with AUD, phosphatidylethanol (PEth) levels > 20 mg/nL, and with polypharmacy (> 5 medications) receiving care at the Atlanta Veterans Affairs Infectious Disease Clinic. Participants will be prescribed the study medication for 12 weeks by an Addiction Physician and will meet with a Clinical Pharmacist to receive a motivational interviewing-based counseling session regarding their personal health risks related to alcohol use in the context of polypharmacy. Feasibility will be assessed by study recruitment, enrollment, and retention, as well as visit attendance and study medication adherence, with the primary outcome being the proportion of patients offered participation who completed enrollment. Acceptability will be assessed through a participant satisfaction questionnaire as well as analyses of qualitative data collected from a subset of participants regarding different components of the intervention and their impact on alcohol consumption. Safety and tolerability will be assessed through review of clinical and laboratory data as well as frequency of adverse events. Descriptive data will compare pre- and post-intervention readiness to change metrics, self-reported and laboratory-based measures of alcohol consumption including PEth, levels of polypharmacy, self-reported and laboratory-based measures of tobacco use, bothersome symptoms, and biomarkers of health related to HIV. Discussion Interventions that address AUD in the context of polypharmacy among PWH are needed. Future research will focus on further evaluating the most promising of these pilot studies through randomized controlled trials to evaluate the efficacy of these novel intervention packages. Trial registration NCT06004830, Date of Registration: August 16, 2023.