Combination interventions to address mental health in low- and middle-income countries (LMICs), are crucial to achieving the UNAIDS 95-95-95 targets as one in four adolescents living with HIV (ALWHIV) experience poor mental health and this contributes to suboptimal medication adherence and lack of viral suppression. Yet few evidence-based interventions have been evaluated in sub–Saharan Africa (SSA), the region where the majority of the 1.7 million ALWHIV reside. The Streamlined Treatment and Evidence-based Adolescent counseling and Medication Support (STREAMS) project will evaluate if our streamlined combination intervention approach to mental health screening, provision of evidence-based interpersonal psychotherapy groups (IPT-G), and evidence-based family strengthening, and medication counseling is feasible and efficacious for ALWHIV in Uganda.