Physical and psychosocial changes during adolescence could influence the psychological well-being and adherence to antiretroviral therapy (ART) of adolescents living with HIV. However, few studies have assessed these two important issues in Zambia. This study aimed at addressing this gap by examining adolescents' depressive symptoms and ART adherence. This was a mixed-methods study conducted from April to July 2014. We recruited 200 adolescents, ages 15 to 19, who were already aware of their HIV status. We measured depressive symptoms using the short form of the Center for Epidemiologic Studies Depression Scale, and self-reported three-day adherence to ART. We performed logistic regression analysis to identify factors associated with depressive symptoms and non-adherence to ART. For qualitative data, we examined challenges over ART adherence using thematic analysis. Out of 190 adolescents, 25.3% showed high scores of depressive symptoms. Factors associated with depressive symptoms were unsatisfactory relationships with family (Adjusted Odds Ratio [AOR] 3.01; 95% Confidence Interval [CI] 1.20-7.56); unsatisfactory relationships with health workers (AOR 2.68; 95% CI 1.04-6.93); and experience of stigma (AOR 2.99; 95% CI 1.07-8.41). Of all participants, 94.2% were taking ART, but 28.3% were non-adherent. Factors associated with non-adherence to ART were loss of a mother (AOR 3.00; 95% CI 1.05-8.58) and lack of basic knowledge about HIV (AOR 3.25; 95% CI 1.43-7.40). Qualitative data identified the following challenges to ART adherence: management of medication, physical reactions to medicine, and psychosocial distress. The evidence suggests that depressive symptoms and non-adherence to ART were priority issues in late adolescence in Zambia. Health workers should be aware of these issues, and the care and treatment services should be tailored to respond to age-specific needs.
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