Several interventions have shown benefits in improving mental health problems such as depression which is common in people living with HIV. However, there is a paucity of evidence on the effect of these interventions in improving HIV treatment outcomes. This study aimed at bridging this evidence gap and guiding the integration of depression and HIV management, particularly in rural health settings of Cameroon. We carried out a cluster-randomized intervention study targeting persons aged 13 years and above who had been on antiretroviral treatment for 6–9 months. Participants were followed up for 12 months during which those in the intervention group underwent routine screening and management of depression. Comparisons were done using the two-way ANOVA and Chi-squared test with significance set at 5%. Overall, 370 participants with a median age of 39 years (IQR: 30–49) were enrolled in this study. Of these, 42 (11.3%) were screened with mod