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Aim: To evaluate the influence of social and clinical aspects in terms of medication adherence of patients co-infected with HIV/Tuberculosis. Method: This is a descriptive cross-sectional study using a quantitative approach, performed in a public institution in the state of Rio Grande do Norte, Brazil, in the period from August 2014 to January 2015, with 34 users co-infected with HIV/TB. The instruments used were: sociodemographic and clinical assessment; the Morisky-Green test and evaluation of the difficulty level for adherence. Results: adherence to treatment was significantly associated with the time of diagnosis for HIV over five years, with moderate difficulty regarding medication adherence (p=0.019). Conclusion: professionals need to consider the compliance with treatment in the general context in which users are found, including the associated factors and the actions planned by the service significantly influencing the treatment outcome. [ABSTRACT FROM AUTHOR]