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Objectives: To evaluate the association between variables related to stress, reasons, and depression, and adherence to treatment in HIV-positive individuals, and to analyze the robustness according to a theoretical psychology model., Methods: This was a cross-sectional study of 25 female and 39 male HIV-positive participants receiving services at the Outpatient Center for Prevention and Treatment of HIV/AIDS and Sexually-transmitted Diseases (Centro Ambulatorio para la Prevención y Atención del VIH/Sida e Infecciones de Transmisión Sexual) in Hermosillo, Sonora, Mexico. The psychological variables, the degree of treatment adherence, stress-related circumstances, and the severity of depression were examined. Rates were calculated for the key variables associated with stress, reasons, and depression. The associations among variables were determined by multiple regression., Results: During the month preceding the study, 65.6% of the 64 participants reported having faithfully followed the prescribed treatment, while 34.4% had failed, in some way, to follow the treatment (chi(2) = 6.250; P = 0.012). Regression analysis found that there was only one combination, an intermediate level of stress linked to tolerance of uncertainty and low levels of depression, that was significantly associated (F [3.58] = 3.298; P = 0.027) with adherence to treatment; the combination of these two variables explained 38.2% of the total variance found., Conclusions: The combination of stress levels with tolerance of uncertainty and depression could be used as a predictor for true compliance with prescribed treatment plans. These results should be taken into account when designing intervention and treatment-adherence campaigns in HIV-positive individuals.