Protocol plans three open-label AUD medication pilots in adults with HIV

A published protocol describes three planned open-label pilot studies of spironolactone, varenicline and semaglutide for alcohol use disorder among adults with HIV who are taking more than five medications. The separate pilots are intended to assess whether each off-label medication, paired with counseling delivered by a clinical pharmacist, can be implemented and tolerated in this population. They will also examine participant acceptability, adherence and descriptive changes in alcohol consumption. Because this is a study protocol, it reports planned methods and hypotheses rather than treatment results, and it is not designed to establish efficacy. The trial is registered as NCT06004830, with registration dated August 16, 2023.

The investigators are conducting the planned work through the HIV and Alcohol Research Center focused on Polypharmacy, or HARP, and aim to recruit 60 adults receiving care at the Atlanta Veterans Affairs Infectious Disease Clinic. Twenty participants are planned for each medication-specific pilot. Eligibility criteria include alcohol use disorder, a phosphatidylethanol, or PEth, concentration above 20 mg/nL, and polypharmacy, defined in the protocol as taking more than five medications. Each study medication would be prescribed for 12 weeks by an addiction physician. Participants would also meet with a clinical pharmacist for a motivational interviewing-based counseling session concerning their personal health risks associated with alcohol use in the context of polypharmacy.

Feasibility will be evaluated through recruitment, enrollment, retention, visit attendance and adherence to the study medication. The protocol identifies the proportion of patients offered participation who complete enrollment as the primary feasibility outcome. Acceptability will be examined through a participant satisfaction questionnaire and analysis of qualitative information from a subset of participants. The qualitative material is intended to capture participants’ views of the intervention’s different components and their perceived impact on alcohol consumption. These measures address whether the intervention can be delivered in the intended clinic and whether participants regard it favorably, rather than whether it produces a clinically proven reduction in drinking.

Safety and tolerability will be assessed by reviewing clinical and laboratory information and recording the frequency of adverse events. The investigators will also make descriptive comparisons before and after the 12-week intervention. Planned measures include readiness to change, self-reported and laboratory-based indicators of alcohol consumption, PEth concentration, polypharmacy, self-reported and laboratory-based measures of tobacco use, bothersome symptoms, and biomarkers of health related to HIV. The absence of a randomized comparison group and the open-label design mean that any before-and-after differences cannot establish that a medication caused a change in alcohol consumption. The protocol also does not provide evidence that any of the three medications is safe, tolerable or effective for adults with HIV and polypharmacy.

The researchers hypothesize that the three off-label medications, each combined with the pharmacist-delivered behavioral intervention, will be feasible, acceptable, safe and tolerable and will be associated with changes in alcohol consumption. Those statements are prospective expectations, not observed findings. The study’s limited scope—three separate pilots, 60 participants in total, 20 per medication, one Veterans Affairs clinic and a 12-week treatment period—means that it is intended to provide preliminary operational and descriptive information. The investigators state that future research will evaluate the most promising intervention package in randomized controlled trials. Until such trials produce comparative results, the protocol supports planning and feasibility assessment, not conclusions about the clinical benefit of spironolactone, varenicline or semaglutide for this population.

Subject of Research: Three planned open-label pilot studies of off-label medications for alcohol use disorder in adults with HIV and polypharmacy

Article Title: 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

Article References: Haque, L. Y., Maisto, S. A., Weiss, J., Marconi, V. C., Hsieh, E., Garcia, A., Womack, J. A., Kidwai-Khan, F., Tang, Y., Dziura, J., Leggio, L., Bryant, K., Justice, A. C., Fiellin, D. A., & Edelman, E. J. (2026). 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. Addiction Science & Clinical Practice. https://doi.org/10.1186/s13722-026-00728-5

Image Credits: AI Generated

DOI: 10.1186/s13722-026-00728-5

Keywords: HIV, alcohol use disorder, polypharmacy, spironolactone, varenicline, semaglutide, open-label pilot, clinical protocol, PEth, Veterans Affairs, Feasibility, acceptability