The current study examines the relationship between negative consequences of alcohol use, adherence self-efficacy, medication adherence, and biological markers of HIV health (CD4 count and viral load). A total of 275 HIV-positive men and women with alcohol use disorders were surveyed using Audio-CASI measures and time line followback interviews. Findings from a structural equation model suggest that negative consequences related to alcohol use did not directly impact HIV health. Adherence self-efficacy had direct effects on viral load, but not CD4 count. Mediation analyses indicated that self-reported adherence partially mediated the relationship between adherence self-efficacy and viral load. Cognitive-oriented interventions aimed at facilitating adherence self-efficacy may be effective in improving both medication adherence and HIV health. If facilitating confidence improves HIV health, then health care providers can make a strong impact by spending a few short minutes themselves and/or partnering with behavioral health clinicians using techniques like motivational enhancement.