Opioids are often prescribed for chronic pain, and opioid risks such as overdose and death are heightened when opioids are co-prescribed with other sedating medications. We investigated factors associated with chronic opioid prescription, alone and in combination with benzodiazepines and muscle relaxants, in a clinical cohort of individuals with HIV. We used multivariable logistic regression models to determine participant clinical and demographic characteristics that are associated with chronic prescription of opioids or chronic co-prescription of opioids with sedating medications. Among 1474 participants, chronic prescription of opioids occurred in 253 individuals (17.2 %), and chronic co-prescription occurred in 90 individuals (6.1 %). Age >50, public insurance as compared to private insurance, and symptoms of depression and anxiety were significantly associated with chronic opioid prescription and chronic co-prescription. Our findings raise concern that opioid prescription and co-prescription of sedating medications occurs disproportionately in patients for whom use is riskier.