In 2014, UNAIDS set ambitious goals to achieve 90% virologic suppression rates among individuals on antiretroviral therapy (ART). In Zimbabwe, this is an ambitious target, particularly among adolescents; less than 5% of human immunodeficiency virus (HIV)-infected individuals received HIV viral load (VL) testing in 2015, as reported by Ministry of Health and Child Care in Zimbabwe and treatment failure rates among adolescents range between 25-37% (Makadzange et al., 2015). Adolescents failing ART also have high rates of drug resistance. Scalable strategies to facilitate improved VL monitoring, adherence support, and genotyping for those with persistent viremia are urgently needed. The investigators have shown that dried blood spot (DBS) samples can be used for routine VL monitoring on existing technologies (Makadzange et al., 2017) They have also adapted an evidence-based, widely-used, cognitive behavioral therapy (CBT) adherence intervention (Life-Steps) for use in Zimbabwe and have identified a low-cost genotyping strategy that can facilitate detection of drug resistance mutations (DRMs) using already existing real-time polymerase chain reaction technology. The primary study objective is to determine if implementation of a package of care that includes DBS-based VL monitoring, coupled with an evidence-based intervention to improve ART adherence using cognitive-behavioral principles as well as genotyping for individuals with persistent viremia decreases 12-month virologic failure rates among HIV-infected adolescents compared with standard of care (SOC). The investigators hypothesize that the proposed package of care will result in a decrease in virologic failure rates among adolescents. They will also adapt and integrate Nzira Itsva for Adolescents (NI), a cultural adaptation of Life-Steps, into routine care as an adherence support intervention for HIV-infected adolescents, and implement a novel, low-cost genotyping assay using Pan-Degenerate Amplification and Adaptation (PANDAA) of viral ribonucleic acid (RNA) as a point mutation assay for the detection of drug resistance in parallel with Sanger sequencing. Process and cost data will be collected for subsequent cost-analysis. The proposed intervention will be a two-arm, cluster-randomized trial in Mashonaland West and Matabeleland North provinces of Zimbabwe. The units of randomization will be public and largely rural clinics within the provinces, with sites randomized to the intervention or to the SOC. The study is anticipated to show that the use of DBS in routine monitoring of adolescents is feasible, and to show that CBT, if incorporated into routine counselling activities, can complement VL monitoring and genotyping to reduce treatment failure rates and preserve therapeutic options for infected adolescents. The results of this study will have important implications in Zimbabwe and other low-income countries in sub-Saharan Africa with a large proportion of HIV-infected adolescents. The study will include young adolescents aged 10- <14years, as well as older adolescents aged 15-19 years and therefore provide data that will guide implementation of strategies for virologic success in the growing number of perinatally-infected children who are surviving on ART into adolescence, as well as for behaviorally-infected adolescents. The study will be performed within 44 clinics in Matabeleland North and Mashonaland West provinces, and will recruit 828 adolescents. A multidisciplinary consortium with the expertise to conduct this study has been assembled. The consortium includes public health practitioners, a biostatistician, basic scientists with extensive experience in virology and development of novel technologies, HIV clinicians with experience in implementation science, global mental health, and behavioral psychology experts. The consortium will work in partnership with the Ministry of Health (MOH) to implement this protocol and ensure its success.