Depression affects 18–30 % of HIV-infected patients in Africa and is associated with greater stigma, lower antiretroviral adherence, and faster disease progression. However, the region’s health system capacity to effectively identify and treat depression is limited. Task-shifting models may help address this large mental health treatment gap. Measurement-Based Care (MBC) is a task-shifting model in which a Depression Care Manager guides a non-psychiatric (e.g., HIV) provider in prescribing and managing antidepressant treatment. We adapted MBC for depressed HIV-infected patients in Cameroon and completed a pilot study to assess feasibility, safety, acceptability, and preliminary efficacy. We enrolled 55 participants; all started amitriptyline 25–50 mg daily at baseline. By 12 weeks, most remained at 50 mg daily (range 25–125 mg). Median (interquartile range) PHQ-9 depressive severity scores declined from 13 (12–16) (baseline) to 2 (0–3) (week 12); 87 % achieved depression remission (PHQ-9 <5) by 12 weeks. Intervention fidelity was high: HIV providers followed MBC recommendations at 96 % of encounters. Most divergences reflected a failure to increase dose when indicated. No serious and few bothersome side effects were reported. Most suicidality (prevalence 62 % at baseline; 8 % at 12 weeks) was either passive or low-risk. Participant satisfaction was high (100 %), and most participants (89 %) indicated willingness to pay for medications if MBC were implemented in routine care. The adapted MBC intervention demonstrated high feasibility, safety, acceptability, and preliminary efficacy in this uncontrolled pilot study. Further research should assess whether MBC could improve adherence and HIV outcomes in this setting.