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Abstract Background There are approximately 72,000 people living with HIV/AIDS (PLHIV) in Peru. Non-adherence to antiretroviral therapy (ART) is the most important factor for therapeutic failure and the development of resistance. Peru has achieved moderate progress in meeting the 90-90-90 targets, but only 60% of PLHIV receiving ART are virally suppressed. The purpose of this study was to understand ART adherence in the Peruvian context, including developing sociodemographic and clinical profiles, evaluating the clinical management strategies, and analyzing the relationships between the variables and adherence of PLHIV managed at a regional HIV clinic in Lambayeque Province (Northern Peru). Methods This was a cross-sectional study with 180 PLHIV adults, non-randomly but consecutively selected with self-reported ART compliance (78.2% of the eligible population). The PLHIV profile (PLHIV-Pro) and the Simplified Medication Adherence Questionnaire (SMAQ) were used to collect sociodemographic information, clinical variables, and data specific to ART adherence. Descriptive analysis of sociodemographic and clinical characteristics was performed. Bivariate analysis was performed with the Mann–Whitney test, Chi square test, and Yates correction. Results The 180 PLHIV sample included 78.9% men, 49.4% heterosexual, 45% with a detectable HIV-1 viral load less than 40 copies/ml, 58.3% not consistently adherent, and only 26.1% receiving Tenofovir + Lamivudine + Efavirenz. Risk factors significant for non-adherence included concurrent tuberculosis, discomfort with the ART regime, and previous pauses in ART. Multivariate analysis of nested models indicated having children is a protector factor for adherence. Conclusions Self-reported adherence appeared to be low and the use of first-line therapy is not being prescribed homogeneously. Factors associated with nonadherence are both medical and behavioral, such as having tuberculosis, pausing ART, or experiencing discomfort with ART. The Peruvian government needs to update national technical standards, monitor medication availability, and provide education to health care professionals in alignment with evidence-based guidelines and international recommendations. Instruments to measure adherence need to be developed and evaluated for use in Latin America.