Panic disorder (PD) occurs at greater rates among those with HIV compared to those without HIV. Rates of PD may be elevated among those with opioid dependence (persons who inject drugs, PWID). Persons with HIV experience common bodily symptoms as a result of the disease and these symptoms overlap with those of PD which may contribute to a "fear of fear" cycle present in PD. HIV-positive, PWID represent an at-risk population in terms of poor medication adherence. HIV symptoms and HIV medication side-effects commonly overlap with panic symptoms and may affect HIV medication adherence. The aim of this investigation was to examine the impact of PD on HIV-related symptom distress and HIV medication adherence in HIV-positive adults (N = 131) in treatment for opioid use. Those with a diagnosis of PD evidenced greater levels of HIV symptom distress and lower levels of medication adherence than those without current PD. Results highlight the clinical importance of assessing for and treating PD among individuals with HIV that are prescribed antiretroviral therapy. Future work would benefit from examining observed associations longitudinally and identifying potential mechanisms involved.