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Background: Consistent with the global trend, youth with HIV (YWH) in Nigeria have high rates of viral nonsuppression. Hence, novel interventions are needed., Setting: Infectious Diseases Institute, College of Medicine, University of Ibadan, Nigeria., Methods: In a single-arm trial, participants aged 15-24 years received 48 weeks of a combination intervention, comprising daily 2-way text message medication reminders plus peer navigation. The primary outcome measure was viral suppression less than 200 copies/mL. The secondary outcome measures included self-reported adherence on a visual analog scale and medication possession ratio, each dichotomized as ≥90% (good) or <90% (poor) adherence. The outcomes were analyzed using McNemar test. Retention in care, intervention feasibility and acceptability, and participants' satisfaction were also assessed., Results: Forty YWH (50% male participants) were enrolled: mean age 19.9 years (SD = 2.5), 55% perinatally infected, and 35% virologically suppressed at baseline. Compared with baseline, the odds of virologic suppression was higher at 24 weeks (odds ratio = 14.00, P < 0.001) and 48 weeks (odds ratio = 6.00, P = 0.013). Self-reported adherence (≥90%) increased from baseline at 24 weeks (63%, P = 0.008) and 48 weeks (68%, P = 0.031). Medication possession ratio ≥90% increased at weeks 24 and 48 (85% and 80%, respectively), achieving statistical significance at 24 weeks alone (P = 0.022). Retention in care at 48 weeks was 87.5%. All (37/37) participants at week 48 were fully or mostly satisfied with the intervention., Conclusion: Daily 2-way text message reminders plus peer navigation is a promising combination intervention to improve viral suppression among YWH in Nigeria., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)