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The goals of this study were to assess retention on antiretroviral therapy (ART) and to identify predictors of loss to follow-up (LTFU) among people living with HIV (PLHIV) in Senegal. HIV-positive individuals presenting for initiation of ART in Dakar and Ziguinchor were enrolled and followed for 12 months. Data were collected using interviews, clinical evaluations, laboratory analyses, chart review, and active patient tracing. Of the 207 individuals enrolled, 70% were female, 32% had no formal education, and 28% were severely food insecure. At the end of the follow-up period, 58% were retained on ART, 15% were deceased, 4% had transferred care, 5% had migrated, and 16% were lost to follow-up. Enrollment in Ziguinchor (OR 2.71 [1.01-7.22]) and severe food insecurity (OR 2.55 [1.09-5.96]) were predictive of LTFU. Sex, age, CD4 count, BMI <18.5, country of birth, marital status, number of children, household size, education, consultation with traditional healers, transportation time, and transportation cost were not associated with LTFU. The strongest predictor of severe food insecurity was lack of formal education (OR 2.75 [1.30-5.80]). Addressing the upstream drivers of food insecurity and implementing strategies to enhance food security for PLHIV may be effective approaches to reduce LTFU and strengthen the HIV care cascade in the region. [ABSTRACT FROM AUTHOR]