Introduction: In Indonesia, the Human Immunodeficiency Virus (HIV) is a serious health concern. Since HIV/AIDS patients must adhere to anti-retroviral (ARV) treatment for the rest of their lives, treatment and care must have this as their main objective. Objective: This study was to identify the factors that influence People Living with HIV/ AIDS (PLWHA) to adhere their anti-retroviral (ARV) medication consumption and the determinants of this adherence. Method: This study uses a descriptive analytic design with cross-sectional approach, which provides an overview of adherence factors in taking ARV, such as gender, education, occupation, knowledge, family support, instructional perception, and motivation. This study was taken in Mejobo District, Kudus Regency, and Indonesia. This study's sample was taken using the total sampling technique involving 33 respondents. Result: This study showed that instructional perception is a determining factor in adherence to ARV medication use with OR of 2.746, followed by education (OR 2.24) and education (OR 2.197). Conclusion: The necessity of education on how to consume ARVs is critical, thus medical professionals must be more active in ensuring patient comprehension and motivation so that ARV therapy is sustained.