South Africa (SA) has the most people living with HIV/AIDS (PLWH) globally and prevalent alcohol use. Beliefs that mixing alcohol and antiretroviral therapy (ART) can lead to adverse reactions may promote ART nonadherence. Healthcare providers (n = 11) and patients (n = 19) recruited from primary HIV and substance use care in SA described their messages, beliefs, and behaviors around simultaneous use of alcohol and ART. Transcripts were analyzed using thematic analysis: (1) most providers indicated a message shift to reflect harm reduction principles: PLWH should manage alcohol use but not let it interfere with taking ART; however, (2) patients recalled conflicting messages from their providers and some displayed interactive toxicity beliefs and behaviors. Despite progress demonstrated by 2016 national adherence guidelines and shifted provider messaging, interactive toxicity beliefs remain a barrier to ART adherence. Results have implications for the adaptation of adherence counseling to minimize the impact of alcohol use on HIV treatment.